QUADRENNIAL REPORT - Instituto Nacional de Ciência e ...

INCT de Biologia Estrutural e Bioimagem

QUADRENNIAL REPORT 2013, 2014, 2015 and 2016

INBEB 2013-2016 QUADRENNIAL REPORT

1

INCT de Biologia Estrutural e Bioimagem

QUADRENNIAL REPORT 2013, 2014, 2015 and 2016


2

Headquarters: UFRJ - Universidade Federal do Rio de Janeiro

Coordinator: Jerson Lima Silva Instituto de Bioquímica Médica, UFRJ

Vice-Coordinator:

Wanderley de Souza Instituto de Biofísica Carlos Chagas Filho, UFRJ


3

SUMMARY

1.1 Our mission .................................................................................................................6

1.2 INBEB’s history..........................................................................................................6

1.3 INBEB’s Facilities ......................................................................................................7

- CENABIO I ................................................................................................................8

- CENABIO II ...............................................................................................................9

- CENABIO III ...........................................................................................................12

2.1 Associate Laboratories ..............................................................................................16

2.3 Steering committee ...................................................................................................18

2.4 Brazilian institutions .................................................................................................18

2.5 Working up close with members ..............................................................................19

2.6 Awards and scientific excellence ..............................................................................20

Awards of excellence ..................................................................................................20

Award in tribute to Thaïs Souto-Padrón .....................................................................20

Cooperation with a Nobel laureate .............................................................................21

AL 1. Associated Laboratory of Virus and Cancer Structural Biology ......................24

AL 2 - Associated Laboratory of Structural Biology of Cardiac and Amyloidogenic

Proteins ....................................................................................................................................38

AL 3 - Associated Laboratory of Proteins Structure Determination by NMR............46

AL 4 - Associated Laboratory of Pharmacologic Proteomic ......................................54

AL 5 - Associate Laboratory of Nuclear Magnetic Resonance, Organic Synthesis and

Molecular Modeling .................................................................................................................61

LA 06 - Associate Laboratory of Proteins and Proteomic Heterologous Expression .80

LA 7- Associated Laboratory of Proteins Biochemistry .............................................85

AL 8 - Associated Laboratory of Macromolecules Crystallization ............................91

AL 9 - Associate Laboratory of Cellular Ultrastructure Hertha Meyer ......................94

AL 10 - Associated Laboratory of Genomic, Proteomic, Modeling and Nanoscopy of

Biological Systems .................................................................................................................104

LA 11- Associated Laboratory of Microscopy .........................................................109


4

AL 12 - Associated Laboratory of Cellular Ultrastructure ....................................... 114

AL 13 - Associated Laboratory of Structural Biothecnology ................................... 121

AL 14 - Associate Laboratory of Structural Biology ............................................... 127

AL 15 - Associated Laboratory of Microscopy CETENE - Coodinator: ................. 133

AL 16 - Associate Laboratory of Molecular And Cellular Cardiology .................... 140

AL 17.- Associated Laboratory of Ion transport physiology in health and disease .. 146

AL 18 - Associated Laboratory of Immunology ...................................................... 156

AL 19 - Associated Laboratory of Cellular and Molecular Neurology .................... 161

AL 20 - Associated Laboratory of Inflammation and Metabolism .......................... 167

Other events supported by INBEB ........................................................................... 184

Regular seminars .......................................................................................................... 188

Training and teaching human resources ....................................................................... 192

- Doctoral thesis completed: ..................................................................................... 193

- Masters theses completed: .......................................................................................... 210

- Science fairs: .......................................................................................................... 231

- Vacation (winter and summer) workshops ............................................................. 235

- INBEB’s partner school wins scientific award ...................................................... 238

- Adoption of a public school ................................................................................... 239

Other initiatives from INBEB members ....................................................................... 240

- Audiovisual productions ........................................................................................ 240

-Educational books ................................................................................................... 241

INBEB website and social media ................................................................................. 242


5

Introduction


6

1. Presentation

1.1 Our mission

The National Institute of Science and Technology for Structural Biology and

Bioimaging is a pioneering initiative with a mission to generate an infrastructure for the

advanced study of the structures of biological systems, from the macromolecular level to the

organisms in their entirety, making use of the most advanced analytical techniques, as well as

images of the highest available resolution. Another key objective of the Institute is to contribute

to the training of researchers in Structural Biology and Bioimaging at various levels (from

undergraduate to post-doctoral).

Therefore, INBEB promotes inter and multidisciplinary activities, integrating

conventional areas such as biophysics, parasitology, microbiology, immunology, biochemistry,

pharmacology, chemistry and computational biology as well as extending their boundaries. This

allows for greater interaction between different groups to solve biological problems. We have

become increasingly aware of the need to integrate studies on the structure of macromolecules

and how they combine to form biological units, which in turn are organized into different cell

types, constituting the different tissues and organs found in living beings.

Our main goal is to enhance the understanding of biological structures at different

levels, from the macromolecular to the whole-organism level, which has led us to assemble a

nucleus of research groups with proven leadership in biomedical and biotechnological research

in Brazil. In addition, our mission is to create conditions in which this infrastructure can be

integrated into similar but less complex initiatives in different regions of the country, through

the involvement of a large number of smaller institutions. We have also extended our interaction

with the private sector through a partnership with the Instituto D’OR (IDOR) in order to

reinforce and expand our ability to do translational research.

1.2 INBEB’s history

INBEB started with the efforts of Prof. Jerson Lima da Silva, when he organized the National

Center of Nuclear Magnetic Resonance in 1997 (which in 2002 incorporated the name Jiri

Jonas). The NCNMR already had a set of equipments for elucidation of macromolecular

structures. In 2008, funds from the Millennium Institute allowed the purchase of the powerful

800 MHz spectrometer, a unique resource in Latin America. From this point on, Prof. Lima da

Silva and other researchers (particularly Prof. Wanderley de Souza), felt the need to expand the

Center’s scope in order to incorporate imaging cells and even small animals.


7

In 2009, the Center took part in the National Institute of Science and Technology of Structural

Biology and Bioimage (INBEB), led by Prof. da Silva. Such a move allowed for the

inauguration of CENABIO II, for imaging small animals, in May 2010. Later on, in 2013, the

construction of a third center dedicated to microscopy began, with the goal of properly storing

equipment already used by INBEB members, but which were dispersed through several

laboratories in the UFRJ. This new site also allowed for the implementation of CENABIO III in

mid-2015.

In November 4, 2013, the Bioimaging Center, which houses CENABIOs I, II and III (the ladder

still in early stages of construction), was granted a “nucleus” status within the Federal

University of Rio de Janeiro. Professor Adalberto Ramon Vieyra was elected head of the

nucleus, which is one of the seven members of INBEB’s steering committee. As part of

INBEB, the nucleus received more institutional support from the university.

Thus, the new National Nucleus of Structural Biology and Bioimagem in UFRJ allowed for a

broader institutionalization and formalization of CENABIOs activities, increasing its

performance and collaborations with the university. In addition, the Nucleus regiment includes a

shared workload, which promotes the inclusion of researchers from all over the country, with no

harm to their primary affiliations.

1.3 INBEB’s Facilities

As explained mentioned, the headquarters of the INBEB are located on the main

campus of the Universidade Federal do Rio de Janeiro (UFRJ). The equipment is available not

only to the groups that belong to the INBEB, but also to the general scientific community both

within Brazil and abroad. The instruments are frequently utilized by our Mercosur colleagues,

who are developing projects that take advantage of our state-of-the-art infrastructure and central

location. Also, as members of a partner institution, INDOR researchers, have access to the

small-animal bioimaging infrastructure at the INBEB and INBEB’s researchers have access,

when needed, to an array of imaging equipment for human subjects in the Rede D’OR.

The INBEB facilities (equipment, animal-care facilities and research core labs) are

hosted in three units, each one with its own headquarters building, which constitute the

following National Bioimage Centers (CENABIOs):

CENABIO I, or Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas (Jiri Jonas

National Center for Nuclear Magnetic Resonance);

CENABIO II, which houses the equipment for small-animal bioimaging;


8

CENABIO III, which had just finished the last phase of construction with funds provided by

Pro-INFRA at UFRJ (FINEP/MCT). This unit now houses several equipment for electronic,

confocal, multiphoton, and atomic force microscopy.

- CENABIO I

CENABIO I is dedicated to the elucidation of macromolecular structure, combining the

early NMR equipment (originally part of the CNRMN) with a Bruker DRX 600 MHz

spectrometer, upgraded to the digital system AVANCE, both acquired with funds granted for

INBEB equipment. This infrastructure allows for the full use of four channels, inverse triple

resonance probes, and the inverse triple resonance cryoprobe. With such an upgrade, the NMR

equipment is now state-of-the-art and its sensitivity and resolution are equivalent to that of a

new spectrometer.

Furthermore, the Bruker Avance III 800 MHz spectrometer, which has four channels

and an inverse triple resonance probe, has also been amplified and diversified. Resources from

the INBEB have allowed for maintenance of the spectrometers and and acquisition of

supplementary equipment (e.g. backup power supplies, unit upgrades, probes, high-pressure

NMR equipment, air conditioners, etc.). These additions were crucial to our ability to keepthe

NMR Center open 24 hours per day for use by Associate Laboratory members and by a large

number of researchers, who are not affiliated with the INBEB.

Another equipment that was widely used was the The Bruker DRX 400-MHz wide-bore

instrument, which is equipped with three channels, inverse triple resonance probes, a broadband

inverse probe, and magic angle spinning (MAS) for investigation of solid samples. Two new

spectrometers just purchased (700 and 500 MHz) will extend the range of applications to solid-

state NMR. In addition, a new super-powerful 900MHz Nuclear Magnetic Resonance (NMR)

equipment, the first one in Latin America, just arrived in December 2016. The equipment was

purchased with FINEP funding through FNDCT Pro-Infra and. Once fully installed, it will be

made available to the entire scientific community.

NMR spectrometers room (CENABIO I). Professors in charge: Fábio Almeida and Ana Paula V alente.


9

- CENABIO II

During the consolidation phase, the division for small-animal imaging was the one

receiving the most significant investment. The construction of CENABIO II was completed in

May 2010, and INBEB resources were used to install wiring and to purchase equipment

required to support the imaging instruments. Altogether, the CENABIO II building brings a

broad range of bioimaging instruments for small animals.

CENABIO II building.

Also, the 7-Tesla magnet used for magnetic resonance imaging (MRI) of small animals

has been available for use since May, 2010. This equipment allows for morphological and

functional analyses of organs and systems in live animals (especially mice and rats, the

experimental animals most often used in biomedical research). Nuclear magnetic resonance

imaging is a non-invasive, non-destructive technique that allows investigators to monitor the

morphology and in some cases the organ function of animals over time, without the need to

sacrifice the such animals.

7 Tesla, 210 Bore Actively Screened Refrigerated Magnet System . Varian, inc. Nmr systems. Professor in charge: Fernanda Tovar Moll.


10

Other bioimaging equipment previously acquired using other funds, are now in the

facilities of the new CENABIO II building, which contains the appropriate supporting

infrastructure for efficient use by INBEB researchers and external users. A 110-KVA generator

and backup power supplies protect the equipment and ensures no interruptions during

procedures.

The following equipment is completely installed:

High-resolution ultrasound equipment, designed to acquire high-resolution images from

small animals, enabling for example the visualization of embryonic development in mice by

monitoring organs such as the heart, liver, and kidneys.

Ultrasound equipments. Equipment I: Vevo 770-120. Visual sonics, Toronto, Canadá. Equipment II: MyLab® 30 CV. Biosound Esaote, Inc. Usa. Equipment III : Caris plus. Biosound Esaote, Inc. Usa. Professor in charge: Emiliano Medei.

A bioluminescence and fluorescence detection system for use in live animals that allows

us to visualize cells labeled with enzymes (such as luciferase) that activate luminescent

molecules, such as luciferin, or fluorescent labels. Use of labeled cells or pathogens makes it

possible to track their dissemination when injected into live animals.

Ivis Lumina System. Xenogen corp, CA, EUA.

Professor in charge: Emiliano Medei.


11

Scintigraphy equipment for small animals (PET/SPECT/CT) was recently acquired with

federal and state funds (MS-Decit/FAPERJ).. This equipment allows us to detect radiolabeled

molecules and cells at a resolution of 2 millimeters. It is coupled to a computerized tomography

scanner, which will allow us to overlay 3D SPECT images (single photon emission

computerized tomography) with the computerized tomography images in real time. This

equipment is particularly useful in studying biodistribution of labeled molecules, a technique

that is especially important in evaluating new drugs.

Model: triumph® Ii – pet/spect/ct system, Ge. Professor in charge: Alysson Roncally Carvalho.

Other instruments available in CENABIO II include a FACSAria flow cytometer, which

is used for cell sorting in awide range of applications. CENABIO II also houses about 1300

animals in 387 microisolator cages for mice, 60 microisolator cages for transgenic mice and 72

cages for rats.

BD Facsaria™. Professor in charge: Emiliano Medei.


12

- CENABIO III

Although this facility remains partially under construction, with funds provided by Pro-

INFRA at UFRJ (FINEP/MCT), it already hosts several equipments, concentrating a variety of

microscopes which were scattered throughout several UFRJ laboratories.

CENABIO III building.

CENABIO III currently has the following equipments:

A conventional scanning electron microscope:

Scanning electron microscope Jeol JSM 5310, with maximum voltage 25 kv, magnification range from 35 to 100,000 X. Professor in charge: Kildare Miranda. Technicians: Noêmia Rodrigues and Thiago Luiz de Barros Moreira.


13

A high-resolution scanning electron microscope with a cryo-stage:

Scanning electron microscope Jeol JSM 6340, high resolution with field emission gun. Equipped with cryo-stage, detector of backscattered electrons and secondary electrons. Professor in charge: Kildare Miranda. Technicians: Daniel Iucif and Thiago Luiz de Barros Moreira.

Two conventional transmission electron microscopes:

1- Transmission electron microscope zeiss 902 60 -80 KV with

magnification up to 250,000 X. Equipped with power filter for performing energy loss spectroscopy and obtaining electron spectroscopic imaging. It has a megaview G2 camera (14-bit).

2- Transmission electron microscope zeiss 900, 50 -80 KV with magnification up to 280,000 X. It has a megaview III camera (12 -bit).

Professor in charge: Kildare Miranda. Technicians: Noêmia Rodrigues and Thiago Luiz de Barros Moreira.


14

Two analytical transmission electron microscopes, which provide for collecting

an X-ray emission spectrum for x-ray microanalysis:

Transmission electron microscope Jeol 1200 EX with energy -dispersive X-ray microanalysis, 60 to 120 KV (80KV preferably) with magnification range from 600 to 500,000 X. Equipped with secondary electron detector, transmitted electron detector and X-ray detector for electron microanalysis and mapping. It has a camera megaview III (12 bit). Professor in charge: Kildare Miranda. Technicians: Thiago Luiz de Barros Moreira.

A transmission electron microscope capable of operating at 200 KV:

Transmission electron microscope tecnai g20, d2114, Fei Company, operating at 200 kv. Equipped with tomography holder, able to obtain images around its y axis, at the angular range of -70º to +70º. Configured for electron tomography of biological specimens 200-300 nm thick and allows the acquisition of tomographic series for alignment and 3d reconstruction in speci fic softwares. Professor in charge: Kildare Miranda. Technicians: Thiago Luiz de Barros Moreira.


15

An environmental scanning electron microscope, acquired with INBEB

resources:

Scanning electron microscope quanta 250, Fei Company brand. Tension between 1-30 kv,equipped with a peltier sample cooler (environmental mode) and beam decelerator. Able to work in high (10-2 a 10-4 pa), low vacuum (10 a 130 pa) and environmental mode (10, 400 pa), allowing the observation of non -conductive and / or hydrated materials. Has an X-ray detector for electron microanalysis and mapping, and a detector of backscattered electrons and secondary electrons. Professor in charge: Kildare Miranda. Technicians: Rachel Rachid and Thiago Luiz de Barros Moreira.

In addition, there are several smaller, special-purpose microscopes:

- Two confocal microscopes;

- A multiphoton microscope;

- A multiphoton microscope with a fluorescence correlation spectroscopy system

(FCS);

- A total internal reflection fluorescence (TIRF) microscope;

- Three atomic-force microscopes, including two new state-of-the-art instruments

recently acquired with INBEB funds.

With such a vast array of equipments and resources, the CENABIO III is the most

complete microscopy facility in Latin America, and allows for visualizing proteomic structures

such as amyloid fibers, viral particles, bacteria, and protozoans. It also makes it possible to track

a single viral particle within a living cell, enabling researchers to identify the path the cell

pursues during the infectious process.


16

2. Members INBEB members come from 20 different Associated Laboratories (ALs), from different

universities in seven Brazilian states. They are hundreds of researchers. We also have several

international collaborators who actively participate in INBEB’s research projects and in our

academic activities. Since 2012, INBEB has also gained an prominent international member, the

the 2002 Chemistry Nobel Prize winner, Professor Kurt Wüthrich from the Scripps Research

Institute, USA, and the Federal Institute of Technology of Zurich in Switzerland.

2.1 Associate Laboratories

The ALs are directed by leading researchers in many different fields:

AL1. Associate Laboratory of Virus and Cancer Structural Biology

Coordinator: Jerson Lima Silva, Instituto de Bioquímica Médica/UFRJ.

AL2. Associate Laboratory of Structural Biology of Cardiac and Amyloidogenic Proteins

Coordinator: Débora Foguel, Instituto de Bioquímica Médica/UFRJ.

AL3. Associate Laboratory of Protein Structure Determination by NMR

Coordinator: Fábio Almeida, Instituto de Bioquímica Médica, UFRJ.

AL4. Associate Laboratory of Pharmacologic Proteomics

Coordinator: Russolina Zingali, Instituto de Bioquímica Médica, UFRJ.

AL5. Associate Laboratory of Nuclear Magnetic Resonance, Organic Synthesis and

Molecular Modeling

Coordinator: José Daniel Figueroa Villar, Instituto Militar de Engenharia (IME)

AL6. Associate Laboratory of Proteins and Proteomic Heterologous Expression

Coordinator: Hernán Terenzi, Universidade Federal de Sta Catarina (UFSC)

AL7. Associate Laboratory of Protein Biochemistry

Coordinator: Carlos H. Inácio Ramos, Universidade Estadual de Campinas (UNICAMP)

AL8. Associate Laboratory of Macromolecules Crystallization

Coordinator: Marcelo Santos Castilho, Universidade Federal de Bahia (UFBA)


17

AL9. Associate Laboratory of Cellular Ultrastructure Hertha Meyer

Coordinator: Wanderley de Sousa, Instituto de Biofísica Carlos Chagas Filho (UFRJ)

AL10. Associate Laboratory of Genomics, Proteomics, Modeling and Nanoscopy of

Biological Systems

Coordinator: Paulo Mascarello Bisch, Instituto de Biofísica Carlos Chagas Filho (UFRJ)

AL11. Associate Laboratory of Microscopy

Coordinator: Thaïs Souto-Padrón and Ulysses Garcia Lins, Instituto de Microbiologia Prof

Paulo de Góes (UFRJ)

AL12. Associate Laboratory of Cellular Ultrastructure

Coordinator: Marlene Benchimol, Universidade do Grande Rio (Unigranrio)

AL13. Associate Laboratory of Structural Biotechnology

Coordinator: Celso B. Sant'Anna Filho, Instituto Nacional de Metrologia (INMETRO)

AL14. Associate Laboratory of Structural Biology

Coordinator: Edilene Oliveira da Silva, Universidade Federal do Pará (UFPA)

AL15. Associate Laboratory of Microscopy CETENE

Coordinator: Christina Alves Peixoto, Fundação Oswaldo Cruz and Centro de Tecnologias

Estratégicas do Nordeste (FIOCRUZ, CETENE - Pernambuco)

AL16. Associate Laboratory of Molecular and Cellular Cardiology

Coordinator: Antonio Campos de Carvalho, Instituto de Biofísica Carlos Chagas Filho (UFRJ)

AL17. Associate Laboratory of Ion Transport Physiology in Health and Disease

Coordinator: Adalberto Vieyra, Instituto de Biofísica Carlos Chags Filho (UFRJ)

AL18. Associate Laboratory of Immunology

Coordinator: Júlio Scharfstein, Instituto de Biofísica Carlos Chagas Filho (UFRJ)

AL19. Associate Laboratory of Cellular and Molecular Neurology

Coordinator: Rosalia Mendez Otero, Instituto de Biofísica Carlos Chagas Filho (UFRJ)

AL20. Associate Laboratory of Inflammation and Metabolism

Coordinator: Fernando Augusto Bozza, Instituto de Pesquisa Clínica Evandro Chagas (IPEC-

FOC)


18

2.3 Steering committee

The steering committee is composed of coordinators from seven associated laboratories:

. Coordinator: Jerson Lima da Silva (IBqM/UFRJ) - AL1;

. Vice-coordinator: Wanderley de Souza (IBCC/UFRJ and INMETRO) - AL 09 and 13;

. Antonio Carlos Campos de Carvalho (INC and IBCCF/UFRJ) - AL 16;

. Carlos Ramos (UNICAMP) - AL 7;

. Hernán Terenzi (UFSC) - AL 6;

. Edilene Oliveira da Silva (UFPA) - AL 14;

. Adalberto Ramon Vieyra (IBCCF/UFRJ) - AL 17.

2.4 Brazilian institutions

1. Pará:

- Universidade Federal do Pará (UFPA).

2. Pernambuco:

- Universidade Federal de Pernambuco

(UFPE, PE);

- Centro de Pesquisas Aggeu Magalhães

(CPQAG - FIOCRUZ);

- Centro de Tecnologias Estratégicas do

Nordeste (CETENE).

3. Bahia:

- Universidade Federal da Bahia (UFBA,

BA).

4. Minas Gerais:

- Universidade Federal do Triangulo

Mineiro (UFTM).

5. São Paulo:

- Universidade Estadual de Campinas

(Unicamp, SP).

6. Rio de Janeiro:

- Universidade Federal do Rio de Janeiro

(UFRJ);

- Universidade Federal Fluminense (UFF);

- Universidade Estadual do Rio de Janeiro

(UERJ);

- Universidade Estadual do Norte

Fluminense (UENF);

- Universidade do Grande Rio (Unigranrio);

- Bio-Manguinhos (FIOCRUZ);

- Instituto de Pesquisa Clínica Evandro

Chagas (IPEC, FIOCRUZ);

- Instituto Nacional de Metrologia

(INMETRO);

- Instituto Militar de Engenharia (IME);

- Instituto Nacional de Cardiologia (INC);

Instituto D‟Or de Ensino e Pesquisa

(IDOR).

7. Santa Catarina:

- Universidade Federal de Santa Catarina

(UFSC, SC).


19

2.5 Working up close with members

One of INBEB’s main drives is to promote productive interactions among its ALs and

external collaborators, by creating the infrastructure needed to integrate studies in different

areas. The multidisciplinary facilities encourage the cooperative work in a creative and efficient

way. Understanding the formation of biological structures at their different levels, from the

macromolecular to the whole organism level, is the central goal that has led us to reach out to a

significant number of research groups with proven leadership in biomedical research in Brazil.

INBEB also promotes an important interaction with the corporate world through a

partnership with the D'Or Institute for Research and Teaching (IDOR) and the Rede Labs-D'Or,

in order to expand our ability to do translational research. This has been crucial in initiating

research activities related to small animal magnetic resonance imaging at the INBEB. This

partnership was established in June 2009, with Dr. Fernanda Tovar Moll, the IDOR’s research

director and a member of AL1.

Dr. Moll coordinates the activities and use of the 7-Tesla magnet for MRI studies and is

responsible for implementing IDOR-INBEB collaborative projects, especially those that involve

MRI studies in human beings (located at IDOR) and small animals (located at the INBEB).

Through this partnership, IDOR researchers have access to the small animal bioimaging

infrastructure at the INBEB and the AL researchers have access, whenever they find necessary,

to a wide array of human imaging equipment in the Rede D’OR.

We also maintain a regular seminar program, in which many researchers from different

ALs present their work, as well as promoting one-day workshops and roundtables on special

topics. Moreover, the Annual Meetings organized by the Institute allow our Associate

Laboratories to show their work to other members of the INBEB and to external researchers.

These activities tend to promote new and enjoyable opportunities to interact, improve, and

establish new sources of cooperation. In the following chapters, we will detail the results of our

collaborative pattern of scientific work.

The institute’s website (www.inbeb.org.br) is another important tool in the promotion of

integration among INBEB members. This website provides information about how to access the

INBEB facilities, courses, lectures, news from members and INBEB achievements. In later

chapters we present more details about the meetings, seminars, lectures and outreach strategies.

Finally, since its creation, the Institute has multiplied a network of collaboration among

the different Associate Laboratories and the Multiuser Facilities. Collaborations have increased

mainly as a function of the exchange between students and researchers, something that can be

appreciated in the list of publications in the following chapter. As will be shown, several

publications result from the co-authoring of articles by junior and senior INBEB members from

different groups.

http://www.inbeb.org.br/





20

2.6 Awards and scientific excellence

Awards of excellence

Researcher Débora Foguel, a coordinator of AL2, received, in March 2016, the Nise da

Silveira Award for her contributions to the neurobiology of Alzheimer's Disease. The award is

promoted by the municipality of Rio de Janeiro and the Special Secretariat for Policies for

Women (SPM). During the awards event, a tribute was also paid to seven other women for their

outstanding achievements.

Professor Débora Foguel. Picture by Brazilian Science Academy (ABC).

Award in tribute to Thaïs Souto-Padrón

As a tribute to the Professor Thaïs Souto-Padrón (coordinator of AL 11), the organizing

committee of the XXII edition of the Microbiology and Immunology Week of UFRJ created the

"Thais Souto-Padrón Microscopy Award", dedicated to microscopy images. Professor Souto-

Padrón passed away in July 2016. She was a beloved and admired researcher in the field of

Electronic Microscopy, who accumulated over 120 published papers on the surface antigens of

pathogenic protozoa and their role in interaction with host cells. At the Institute of Microbiology

at UFRJ, Professor Souto-Padrón was responsible for the Microscopy Sector and for the

“Laboratory of Pathogenic Protozoa Surface and its Interaction with Host Cells”. We pay our

tribute in the hope that her legacy of knowledge, dedication, and ethics will live on among her

students and peers.

Professor Thaïs Souto-Padrón at a conference /Poster of the contest


21

Cooperation with a Nobel laureate

We also have several international collaborators who actively participate in scientific

research and in our academic activities. Since 2012, INBEB has also gained an prominent

international member, the the 2002 Chemistry Nobel Prize winner, Professor Kurt Wüthrich at

Scripps Research Institute, USA and the Federal Institute of Technology of Zurich, Switzerland.

Dr Wüthrich develops Nuclear Magnetic Resonance (NMR) methods for studying

biological macromolecules and will serve for the next three years as a visiting researcher at the

INBEB and the Federal University of Rio de Janeiro (UFRJ) – with support from the Brazilian

federal exchange program “Science without borders”.

According to Wüthrich, the infrastructure offered by INBEB is what allows such

partnership to take place. Our facilities allow him to work with the same equipment (unique in

Latin America) that he uses in his laboratories at Scripps Research Institute and at the Federal

Institute of Technology from Zurich.

Two Brazilians - a PhD student and a postdoctoral fellow - have their research work

supervised directly by the Nobel winner. The doctoral thesis, developed by Leonardo Vasquez,

a student at UFRJ, is about the synthesis of proteins within the ribosome. The postdoctoral

fellow, Luana Heimfarth, from the Federal University of Rio Grande do Sul (UFRGS), studies

the application of nuclear magnetic resonance techniques in the field of neurobiology.

Kurt Wüthrich at the INBEB laboratory of Nuclear Magnetic Resonance. Credit:

Cecilia Acioli / “O Globo” newspaper.


22

Science highlights


23

Overview

In the quadrennial of 2013-2016, the members of INBEB ALs have published around a

thousand publications, which consisting of about 990 papers in scientific journals and about 50

books or edited chapters. Around 80 of these resulted from extensive collaborations between

researchers within a single AL or collaboration between different ALs.

- In 2016, there was 223 papers plus 8 books or edited chapters;


- In 2014, there was 288 papers plus 7 books or edited chapters; and


The following is a brief summary of the results from each Associated Laboratory.


24

AL 1. Associated Laboratory of Virus and Cancer

Structural Biology

- Coordinator:

Jerson Lima da Silva - Instituto de Bioquímica Médica (IBqM/UFRJ)

- Researchers from national institutions: Ana Paula Dinis Ano Bom –Fiocruz

Claudia Vitoria M. Gallo – UERJ

Etel Rodrigues Pereira Gimba - UFF

Fernanda Tovar-Moll - ID’Or/UFRJ

Leandro Augusto Oliveira Barbosa -

Universidade Federal de São João del Rei

Luciana Pereira Rangel – FF/UFRJ

Marcela Cristina de Moraes – UFF

Patrícia Souza dos Santos - IBMR

Tuane Cristine R. Gonçalves Vieira – IFRJ

Yraima Moura Lopes Cordeiro - FF/UFRJ

- Collaborators from international

institutions:

Kurt Wütrich – Scripps Research

Institute/USA

- Postdoctoral fellows:

Carolina Cruzeiro da Silva (UFRJ)

Danielly Cristiny Ferraz da Costa (UFRJ)

Elio Anthony Cino (UFRJ)

Erika de C. Rodrigues (ID’Or /UFRJ)

Flávia Bittencourt Brasil (UFF)

Guilherme Augusto P. de Oliveira (UFRJ)

Iaci Nunes Soares (UFRJ)

Livia Goto Silva (ID’Or)

Natália do Carmo Ferreira (UFRJ)

- Doctoral students:

Bruna Valério Gomes (UFRJ)

Carlos Henrique Dumard (UFRJ)

Daniel Menezes (UFRJ)

Diego Szczupak (UFRJ)

Durval S Marques (UFF)

Emily Johanna Castro Fonseca (UFRJ)

Isabelle Simard (UFRJ)

Ivanei Edson Bramati (UFRJ)

Jéssica Martins de Moura Valadares (UFSJ)

Leilismara Sousa Nogueira (UFSJ)

Mafalda Martins (UFRJ)

Marco Túlio Corrêa Pessôa (UFSJ)

Marina Mendes Oliveira (UFSJ)

Mayra de Amorim Marques (UFRJ)

Murilo Martins Pedrote (UFRJ)

Sayonarah Carvalho Rocha (UFSJ)

Tamara Gabriela Fernandes Costa (UFSJ)

Theo Marins (UFRJ)

Vanessa Ferreira Franco (INCA)

- Master's students:

Abigail Cristina da Silva Rezende (INCA)

Carolina Ferraz de Góes (UFRJ)

Giulia Diniz da Silva Ferretti (UFRJ)

Juliana Angelli Nogueira (UFRJ)

Juliana Moreira Soares (UFRJ)

Lucas de Castro Gemal (UFRJ)

Luis Victorino (UFRJ)

Mariana Concentino (INCA)

Murilo Pedrote (UFRJ)

Patrick de Oliveira (UFRJ)

Paula Priscilla F. dos Santos (INCA)

Raiane França Delvalle dos Santos (UFRJ)

Roberta Kele Ribeiro Ferreira (UFRJ)

Roger Borges dos Santos (UFRJ)

- Undergraduate students: Adriani Félix de Lima (UFRJ)

Cristina de Souza Resende (UFRJ)

Cyntia Alves Conceição (UNIGRANRIO)

Fernanda Vaccariello de Menezes (IFRJ)

Juliana Bosco Santos (UFRJ)

Juliana Vieira Bernardo (UFF)

Leonor A. l. Vasconcelos (ID’Or /UFRJ)

Leticia Pinto Felix Valadão (UFRJ)

Lucas Machado Ascari (UFRJ)

Maria Heloisa de Oliveira Freire (UFRJ)

Mariane Pianne (UFF)

Mayra de Amorim Marques (UFRJ)

Nathali Pereira da Costa Campos (UFRJ)

Nicolli Rufino de Queiroz (ID’Or /UFRJ)

Rodrigo Alves da Silva Peres (UFF)

Sarah Maria M. Vieira de Andrade (UFRJ)

Sarah Vivas de Sousa (UFSJ))

Stephanie Medeiros (UFRJ)

Victória Vieira Coelho (IFRJ)

http://lattes.cnpq.br/3010441499735789


25

One of the main subjects of our research is

to understand the mechanisms of protein

folding, protein misfolding, protein-protein

interactions and supramolecular assembly.

Our aim is to decode how these processes

are related to the normal physiological

function of the proteins and to the

development of diseases, such as virus

infections, prion and other

neurodegenerative diseases and cancer.

Exploiting spectroscopic tools such as

fluorescence and NMR, our work with high

pressure in biochemistry and structural

biology has yielded a wealth of new data

and testable models concerning new

concepts for the folding and association of

proteins, virus assembly, protein misfolding

and aggregation. A review on this research

area and its applications was published by

our group recently in the high impact

journal Chemical Reviews (Silva et al,

2014). We also proposed, based on

experimental data, the “push-and-pull”

hypothesis, which reconcile the physical

and chemical unfolding of proteins by

explaining differences between the

molecular mechanisms involved during

these events (Fig. 1; de Oliveira et al.,

2015).

Figure 1 - Urea and high-pressure results in different local unfolding states. The ensemble of dry (DM) and

wet molten globule (WM) intermediates (I) in response to high pressure and urea are different according to

NMR spectroscopy. A schematic of the push-and-pull hypothesis used to explain the mechanisms of the

physical and chemical unfolding of proteins. Water molecules are indicated by red spheres, and urea molecules

are indicated by yellow spheres. Arrows represent the inhomogeneous effect of pressure in contrast to that of

urea.

This subject permeates a significant part of

our group's research lines (specially the

topics 1 to 7, described below). We

highlight some of the most important

findings that we obtained during the four

years’ period covered by this report (2013

to 2016):

1. Virus structure, assembly and cellular

interactions.

We have demonstrated that the entropic

nature of protein interactions and the

changes in hydration are crucial in the

assembly of virus particles and amyloid

aggregates. The studies of the stability of

virus particles using high pressure have

resulted in a new method for obtaining

antiviral vaccines and other applications.

Whole inactivated vaccines (WIVs) possess

greater immunogenicity than split or

subunit vaccines, and recent studies have

demonstrated that WIVs with preserved

fusogenic activity are more protective than

non-fusogenic WIVs. Therefore, we

described the inactivation of human

influenza virus X-31 by high hydrostatic

pressure (HHP). Our results revealed full

viral inactivation with overall preservation

of viral structure and maintenance of

fusogenic activity, thereby conferring

protection against infection. A strong

response consisting of serum

immunoglobulin IgG1, IgG2a, and serum

and mucosal IgA was also detected after

vaccination. Thus, our data strongly suggest

that applying hydrostatic pressure may be

an effective method for developing new

vaccines against influenza A as well as

other viruses. A vaccine based on

pressurized virus represents a simple, fast,

and low cost model that could offer an

important alternative to the large-scale

production of vaccines (Dumard et al.,

2013).


26

2. Prion Diseases.

Prions cause transmissible and genetic

neurodegenerative diseases, such as bovine

spongiform encephalopathy and

Creutzfeldt-Jakob disease (CJD). Many

therapies have been proposed for prion

diseases, but there is still no effective

treatment. The formation of scrapie prion

protein (PrPSc) from cellular prion protein

(PrPC) is the central event of prion diseases

and several molecules work as cofactors in

the conversion process, including

glycosaminoglycans (GAGs). GAGs

exhibit a paradoxical effect, as they convert

PrP into protease-resistant (PrP-res) but

also exert protective activity. In our study,

interaction between heparin and cellular

PrP (PrPC) increased thermal PrP stability,

leading to an 8-fold decrease in

temperature-induced aggregation (Fig. 2).

The interaction of low-molecular-weight

heparin (LMWHep) with the PrP N- or C-

terminal domain affected not only the

extent of PrP fibrillization but also its

kinetics, lowering the reaction rate constant

from 1.04 to 0.29 s 1 and increasing the lag

phase from 12 to 19 h in RT-QuIC

experiments. Our findings explain the

protective effect of heparin in different

models of prion and prion-like

neurodegenerative diseases and establish

the groundwork for the development of

therapeutic strategies based on GAGs

(Vieira et al., 2014).

Figure 2 - Three-dimensional structure and a schematic view of rPrP nucleation-dependent polymerization. A)

Three-dimensional structure of mouse PrP [Protein Data Bank (PDB) entry 1XYX]. The chain is colored

according to amino acid sequence; helix and strands are indicated. B) PrPSc catalyzes the conversion of PrPC

in an autopropagative manner. This reaction is in equilibrium, and PrPSc slowly aggregates to form a critical

nucleus. n, nucleation phase. Once the nucleus is formed, further aggregation becomes thermodynamically

favorable, leading to fibril formation and growth (growth phase). The interaction of LMWHep with the N-

terminal region modulates fibril formation by increasing PrPC stability and changing the equilibrium between

PrPC and PrPSc. Because the conversion of PrPC to PrPSc is necessary at both the nucleation and growth

phases, LMWHep interferes with the kinetics of both. The interaction of LMWHep with the rPrP N- and C-

terminal domains impairs fibrillization and dramatically reduces fibril formation.

We also reported a novel, rapid, specific

and reliable method to screen for new

potential anti-prion agents. PrPC can be

immobilized onto the surface of magnetic

beads and applied in affinity studies to

isolate potential anti-prion agents from

compounds mixtures. The PrPC -coated

MBs retained their capacity to retain active

ligands and the beads can be applied to

successive experiments. This affinity-based

method allowed the isolation of the anti-

prion compound quinacrine, an inhibitor of

PrP aggregation. Therefore, this method can

be applied not only as a first trial of

potential inhibitors of PrPC aggregation, but

also in the screening and identification of

possible cellular cofactors involved in the

deflagration of prion diseases (de Moraes,

2015).

3. Prion-like aggregation of proteins

Protein misfolding results in devastating

degenerative diseases and cancer. Among

the culprits involved in these illnesses are

prions and prion-like proteins, which can

propagate by converting normal proteins to

the wrong conformation. Besides inducing

misfolding of native proteins, prions bind

nucleic acids and other polyanions. We

know little about the structures that occur

between the soluble and fibrillar states,

especially oligomers. It is generally

believed that oligomers are the villains in

toxic gain-of-function mutations in

neurodegenerative diseases. In their


27

functional states, similar multimeric

structures are now thought of as “good”

amyloids, such as the CPEB family of

proteins and Rim4.The distinction between

good and evil might be subtle, and nucleic

acids are key players in the conversion

between the two forms. The appropriate

liquid-liquid phase separation inside the

nucleus and the cytoplasm is the key to

maintaining homeostasis in the cell. The

deterioration of several regulatory

processes occurs during aging and

eventually ensues in most of the

neurodegenerative diseases. However, it is

likely present in other situations as well,

such as chronic traumatic encephalopathy,

which is caused by severe shock to the

head. In the case of cancer, p53 aggregation

appears to sustain the proliferative nature of

tumors, whereas aggregation in

neurodegenerative diseases leads to cell

death, although the proteins appear to share

the same mechanisms for prion-like

conversion. In conclusion, the prions and

prion-like proteins have a desirable or a

pathogenic behavior that is highly

dependent on the interaction with cellular

partners, especially with nucleic acids

(Silva and Cordeiro, 2016).

4. Prion-like proteins in

neurodegenerative disease

Parkinson’s disease is a neurological

disease in which aggregated forms of the α-

synuclein (α-syn) protein are found. Using

high hydrostatic pressure (HHP) coupled

with NMR spectroscopy, we provide

biochemical and structural data on the

mechanism of how pressure affects the

cavity-prone hydrophobic core of α-syn

fibrils and leads to fibril dissociation of

dynamic monomeric species (Fig.3), which

were not detected by conventional

techniques. Different dynamic properties in

the non-amyloid-β component (NAC),

which constitutes the Greek-key

hydrophobic core, and in the acidic C-

terminal region of the protein were

identified. Understanding the molecular

forces behind the formation of pathogenic

fibrils uncovered by pressure perturbation

will aid in the development of new

therapeutics against Parkinson’s disease.

Future therapeutics focused on the blockage

of de novo aggregation and seeding and the

development of new biomarkers for early

diagnosis may represent an effective

strategy to combat PD (de Oliveira et al.,

2016).

Figure 3 - Schematic representation of pressure effects on α-syn fibrils, showing the major findings obtained

by challenging α-syn fibrils with pressure. Structurally modified monomers (SMMs) are shown in red and

remaining fibrils in blue.

4. The prionoid behavior of p53 and its

role as cancer promoter

P53 is a master regulatory protein that

participates in cellular processes such as

apoptosis, DNA repair, and cell cycle

control. p53 functions as a homo tetrameric

tumor suppressor, and is lost in more than

50% of human cancers. Recent studies have

suggested that the formation of mutant p53

aggregates is associated with loss-of

function (LoF), dominant-negative (DN),

and gain-of function (GoF) effects. We

propose that these phenomena can be

explained by a prion-like behavior of

mutant p53 (Silva et al., 2014). Also, p53

aggregates can be internalized by cells and

coaggregate with endogenous p53,

corroborating the prion-like properties of

p53 aggregates. The prion-like behavior of

oncogenic p53 mutants provides an

explanation for its dominant-negative and

GoF properties, including the high

metastatic potential of cancer cells carrying

p53 mutations. The inhibition of p53

aggregation appears to represent a

promising target for therapeutic


28

intervention in patients with malignant

tumors (Costa et al., 2016).

One of our most recent research in this area

investigates the differences between the p53

family of proteins, comprised of p53, p63

and p73. Light scattering, thioflavin T

(ThT) and high hydrostatic pressure (HHP)

assays showed that p53 DNA binding

domain (DBD) aggregates faster and to a

greater extent than p63 and p73 DBDs, and

was more susceptible to denaturation.

Molecular Dynamics (MD) simulations

indicated specific regions of structural

heterogeneity unique to p53, which may be

promoted by elevated incidence of exposed

backbone hydrogen bonds (BHBs). Our

results indicate regions of structural

vulnerability in the p53 DBD (Fig. 4),

suggesting new targetable sites for

modulating p53 stability and aggregation, a

potential approach to cancer therapy (Cino

et al., 2016).

Figure 4. Comparison of the sequences and structures of p53 family DBDs. (c) Superposition of DBD

structures (p53, black, 2FEJ; p63, blue, 2RMN; p73, red, 2XWC)30,33. (d) (top) p53 DBD structure showing

the location of the aggregation prone region (red), and (bottom) PASTA predicted regions of amyloid

aggregation in the p53 family DBDs.

6. Other cancer-related proteins

The ubiquitously expressed c-Abl protein

belongs to the nonreceptor tyrosine kinases

and is a key regulator of cell signaling,

directly involved in chronic myelogenous

leukemia. This protein is regulated by an

autoinhibitory mechanism that involves

shifting from an open to a closed

conformation. The segment of the c-Abl

protein that includes the N-Cap, the SH3

and SH2 domains, the SH3- SH2 connector,

and the SH2-kinase linker comprises the N-

terminal regulatory unit. The SH3 and SH2

domains play a pivotal role as interactive

modules in cell signaling. Our study

provides new insights on the dynamic

behavior for the extreme N-terminal

segment of the c-Abl kinase. Using small

angle x-ray scattering, nuclear magnetic

resonance, and confocal microscopy, we

demonstrate that the N-Cap and the Src

homology (SH) 3 domain acquire µs-ms

motions upon N-Cap association with the

SH2-L domain, revealing a stabilizing

synergy between these segments. The N-

Cap-myristoyl tether likely triggers the

protein to anchor to the membrane because

of these flipflop dynamics, which occur in

the µs-ms time range (Fig. 5). This segment

not only presents the myristate during c-Abl

inhibition but may also trigger protein

localization inside the cell in a functional

and stability-dependent mechanism that is

lost in Bcr-Abl cells, which underlie

chronic myeloid leukemia. This loss of

intramolecular dynamics and binding to the

cellular membrane is a potential therapeutic

target (de Oliveira et al., 2013).


29

Figure 5 - Proposed model for the stability of N-Cap. Left, N-Cap proteolysis in the N-SH3 construct; middle,

N-Cap proteolysis in the ABL-RD; and right, additional stability for the N terminus of the N-Cap (from Gly-2

to Gly-35) would be provided by myristate (sphere representation) binding. Black dots represent cleaved

segments.

Osteopontin (OPN) is a matricellular

protein overexpressed in cancer cells and

modulates tumorigenesis and metastasis,

including in thyroid cancer (TC). The

contribution of each OPN splice variant

(OPN-SV), named OPNa, OPNb and

OPNc, in TC is currently unknown. Our

data demonstrated that OPNa is the

prevalent splice variant in differentiated

thyroid cancer tissues and cell lines, and

that overexpression of OPNa is associated

with poor prognostic and invasive features

in classic papillary thyroid carcinoma.

Moreover, OPNa overexpression in thyroid

cancer cell lines strongly increases cell

migration, invasion and Matrix

metalloproteases activity, evidencing a

major role for OPNa in thyroid cancer

progression features (Fig. 6). Taken

together, these features provide early

evidence that OPNa can potentially mediate

invasive and metastatic potential in classic

papillary thyroid carcinoma (Ferreira et.al.,

2016).

Figure 6: Overexpression of OPNa increases the invasive potential of TC cells in the CAM assay. A. Invasive

capacity of inoculated cells was evaluated by HE and IHC using an anti-tOPN antibody in xenograft CAM

tumor sections. Positive human tOPN immunostaining demonstrating effective overexpression of OPN in

CAM tumors originated from OPNa clones. c643-EV cells forming compacted tumors (score 1; full lines

surrounding the tumor bulk, right panels). OPNa tumors exhibiting loosen structures and single cells invading

the xenograft CAM tumor mesenchyme (arrow heads; score 3, left panels).


30

7. Substances with anti-tumor properties

Cardiotonic steroids are used to treat heart

failure and arrhythmia and have promising

anticancer effects. The prototypic

cardiotonic steroid ouabain may also be a

hormone that modulates epithelial cell

adhesion. Cardiotonic steroids consist of a

steroid nucleus and a lactone ring, and their

biological effects depend on the binding to

their receptor, Na,K-ATPase, through

which, they inhibit Na+ and K+ ion transport

and activate of several intracellular

signaling pathways. In this study, we added

a styrene group to the lactone ring of the

cardiotonic steroid digoxin, to obtain 21-

benzylidene digoxin (21-BD), and

investigated the effects of this synthetic

cardiotonic steroid in different cell models.

In conclusion, the combination of an

styrene group with the lactone moiety of

digoxin produced a cardiotonic steroid, 21-

BD, that enhances Na,K-ATPase catalytic

activity in intact cells and stimulates Na,K-

ATPase mediated signaling events (Fig. 7).

The later include reduction of cell viability

via apoptosis in cancer, but not normal

epithelial cells and increase in the closure

of tight junctions of epithelial cells. The

chemical modification of cardiotonic

steroids with the styrene group has the

potential to provide compounds with new

functional properties that could results

beneficial to treat cancer and perhaps other

diseases in which cell proliferation occurs

(Rocha et al., 2014).

Figure 7- 21-BD increases the expression of Na,K-ATPase in MDCK cells. (A) Protein cell content of the

α1 subunit of the Na,K-ATPase of confluent monolayers of MDCK cells grown on filters in control medium

(white bar) or treated with different concentrations of 21-BD (red bars) for 48 h; upper part of the figure A

shows representative immunoblots of the α1 subunit of the Na,K-ATPase and actin, the lower part the

densitometric analysis. (B and C) Na,K-ATPase α1 subunit stained with a fluoresceinated antibody (B, C,

white) or Topro (blue) to detect the nuclei.

8. Neuroimaging

An important branch of AL1 is the

investigation of clinical, biochemical and

imaging biomarkers of neuronal diseases.

In a clinical approach, this follow-up of the

project is coordinated by the researcher

Fernanda Tovar-Moll, in partnership

between the D'Or Institute for Research and

Teaching (ID’Or) and UFRJ.

Therefore, among the research conducted in

this line, we documented the imaging

findings associated with congenital Zika

virus infection as found in the Instituto de

Pesquisa in Campina Grande State Paraiba

(IPESQ) in northeastern Brazil, where the

congenital infection has been particularly

severe. Brain abnormalities seen in

confirmed (n = 17) and presumed (n = 28)

congenital Zika virus infections were

similar, with ventriculomegaly;

abnormalities of the corpus callosum in

several cases; and cortical migrational

abnormalities in almost all cases.

Intracranial calcifications were most

commonly seen at the gray matter–white

matter junction. The basal ganglia and/or

thalamus were also commonly involved

with calcifications. The skull frequently had

a collapsed appearance with overlapping

sutures and redundant skin folds and,

occasionally, intracranial herniation of

orbital fat and clot in the confluence of

sinuses (Fig. 8). The spectrum of findings is

illustrated to aid the radiologist in

identifying Zika virus infection at imaging.

Also, findings on MR images can lead to

underestimation of the incidence of

calcifications, and evaluation of CT images

makes characterization of subtle

parenchymal abnormalities and corpus

callosum abnormalities difficult. Further

imaging studies on these neonates as they

grow will be helpful in further assessment

of areas involved with the infection (Soares

de Oliveira-Szejnfeld et al., 2016).


31

Figure 8: (a) Axial, (b) sagittal, and (c) coronal fetal T2-weighted MR images in a 29-year-old woman with

confirmed Zika virus infection, initially seen for characteristic rash at 12 weeks of gestational age. (d) Axial

postnatal CT image and (e–g) axial and (h) coronal T2-weighted MR images obtained in her male neonate. The

fetal MR images obtained at 34 weeks (a–c) show asymmetrical ventriculomegaly with a septation in the right

occipital horn (arrowhead on a), small frontal lobes, thinning of the occipital parenchyma (left worse than

right), underdeveloped sylvian fissures, and regions of thickened cortex, as in the right frontal lobe, which is

suggestive of polymicrogyria (arrow on a). There is abnormal, increased signal intensity in the white matter.

The postnatal CT image (d) obtained in the 22-day-old neonate shows punctate calcifications at the gray

matter–white matter junction and asymmetrical ventriculomegaly. The T2-weighted MR images obtained at

26 days (e–h) show septation in the ventricle (arrowhead on e). Note how the right ventricle has relatively

decreased in size compared with the prenatal image, whereas the left ventricle has increased in size. Under-

rotation of the hippocampus (arrowheads on f) is demonstrated. There is clear asymmetry of the gyral pattern

on g, which is relatively smooth in the left occipital region, with abnormal folds in the right occipital and

frontoparietal regions (arrows on g). Subependymal cysts are visualized on h, which are not seen on fetal MR

images.

AL 1 main publications in 2016:

1. ALVES, N.S. ; MENDES, Y.S. ; SOUZA, T.L.F. ; BIANCONI, M.L. ; SILVA, J.L. ; GOMES, A.M.O. ; OLIVEIRA, A.C. . A

biophysical characterization of the interaction of a hepatitis c virus membranotropic peptide with micelles. Biochimica et Biophysica Acta.

Proteins and Proteomics, v. 1862, p. S15709639160000, 2016. http://dx.doi.org/10.1016/j.bbapap.2016.01.003

2. BATISTA, D. P. C. , COSTA, M. M. , GUSMAO, J. C. , AQUINO, P. G. V. , ARAUJO-JUNIOR, J. X. , BARBOSA, L. A. , SANTANA,

C. C. , DORNELAS, C. B. , GRILLO, L. A. M. . Interference in vitro of Aspidosperma macrocarpum extract in the laboratory

colorimetric determinations. Journal of Chemical and Pharmaceutical Research, v. 8, p. 500-504, n. 2016.

3. BERALDO, FLAVIO H. ; OSTAPCHENKO, VALERIY G. ; CAETANO, FABIANA A. ; GUIMARAES, ANDRE L.S. ; FERRETTI,

GIULIA D.S. ; DAUDE, NATHALIE ; BERTRAM, LISA ; NOGUEIRA, KATIANE O.P.C. ; SILVA, JERSON L. ; WESTAWAY,

DAVID ; CASHMAN, NEIL R. ; MARTINS, VILMA R. ; PRADO, VANIA F. ; PRADO, MARCO A. M . Regulation of Amyloid β

oligomer binding to neurons and neurotoxicity by the complex prion protein/mGluR5. The Journal of Biological Chemistry (Print), v. 291,

p. jbc.M116.738286, 2016. http://dx.doi.org/10.1074/jbc.M116.738286

4. CATTANEO, GIULIA ; UBIALI, DANIELA ; CALLERI, ENRICA ; RABUFFETTI, MARCO ; HÖFNER, GEORG C. ; WANNER,

KLAUS T. ; DE MORAES, MARCELA C. ; MARTINELLI, LEONARDO K.B. ; SANTOS, DIÓGENES SANTIAGO ; SPERANZA,

GIOVANNA ; MASSOLINI, GABRIELLA . Development, validation and application of a 96-well enzymatic assay based on LC-ESI-

MS/MS quantification for the screening of selective inhibitors against Mycobacterium tuberculosis purine nucleoside phosphorylase.

Analytica Chimica Acta (Print), v. 943, p. 89-97, 2016. http://dx.doi.org/10.1016/j.aca.2016.09.025

5. CINO, ELIO A. ; SOARES, IACI N. ; PEDROTE, MURILO M. ; DE OLIVEIRA, GUILHERME A. P. ; SILVA, JERSON L. .

Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds. Scientific Reports, v. 6, p. 32535, 2016.

http://dx.doi.org/10.1038/srep32535

6. COSTA, DANIELLY C.F. ; DE OLIVEIRA, GUILHERME A.P. ; CINO, ELIO A. ; SOARES, IACI N. ; RANGEL, LUCIANA P. ;

SILVA, JERSON L. . Aggregation and Prion-Like Properties of Misfolded Tumor Suppressors: Is Cancer a Prion Disease?. CSH

PERSPECT BIOL, v. 8, p. a023614, 2016. http://dx.doi.org/10.1101/cshperspect.a023614

7. DE MATTOS, RM ; PEREIRA, PR ; BARROS, EG ; DA SILVA JH ; PALMERO CY ; DA COSTA NM ; PINTO, L. F. R. ; ETEL

RODRIGUES PEREIRA GIMBA ; HECHT F ; FERREIRA LB ; MACHADO, DE ; OLIVEIRA, FL ; NASCIUTTI . Aberrant levels of

Wnt/β-catenin pathway components in a rat model of endometriosis. Histology and Histopathology, v. 1, p. 1-1, 2016.

http://dx.doi.org/10.14670/HH-11-730

8. DE MORAES, MARCELA; CARDOSO, CARMEN ; SEIDL, CLAUDIA ; MOADDEL, RUIN ; CASS, QUEZIA . Targeting Anti-

Cancer Active Compounds: Affinity-Based Chromatographic Assays. Current Pharmaceutical Design (Print), v. 22, p. 1-1, 2016.

http://dx.doi.org/10.2174/1381612822666160614080506

9. DE OLIVEIRA, GUILHERME A. P. ; MARQUES, MAYRA DE A. ; CRUZEIRO-SILVA, CAROLINA ; CORDEIRO, YRAIMA ;

SCHUABB, CAROLINE ; MORAES, ADOLFO H. ; WINTER, ROLAND ; OSCHKINAT, HARTMUT ; FOGUEL, DEBORA* ;

FREITAS, MÔNICA S. ; SILVA, JERSON L. . Structural basis for the dissociation of α-synuclein fibrils triggered by pressure

perturbation of the hydrophobic core. Scientific Reports, v. 6, p. 37990, 2016. http://dx.doi.org/10.1038/srep37990 *IN

COLLABORATION WITH FOGUEL [AL2]

http://dx.doi.org/10.1016/j.bbapap.2016.01.003

http://dx.doi.org/10.1074/jbc.M116.738286

http://dx.doi.org/10.1016/j.aca.2016.09.025


http://dx.doi.org/10.1101/cshperspect.a023614

http://dx.doi.org/10.14670/HH-11-730

http://dx.doi.org/10.2174/1381612822666160614080506



32

10. DE OLIVEIRA-SOUZA, RICARDO ; MONTEIRO, MYRIAM ; PACHECO, PAULA ; TOVAR-MOLL, FERNANDA ; MATTOS,

PAULO ; MOLL, JORGE ; NAZAR, BRUNO PALAZZO . Right hemisphere dominance for language in a woman with schizophrenia

and a porencephalic cyst of the left hemisphere. NEUROCASE, v. 22, p. 1-8, 2016. http://dx.doi.org/10.1080/13554794.2016.1186199

11. DE PINHEIRO, CRISTIANE GARBOGGINI MELO ; PEDROSA, MAYARA DE OLIVEIRA ; TEIXEIRA, NAIARA CARVALHO ;

ANO BOM, ANA PAULA DINIS ; VAN OERS, MONIQUE M. ; OLIVEIRA, GERALDO GILENO DE SÁ . Optimization of canine

interleukin-12 production using a baculovirus insect cell expression system. BMC Research Notes, v. 9, p. 1, 2016.

http://dx.doi.org/10.1186/s13104-016-1843-7

12. DE SANTANA NUNES, ANA KAROLINA ; RAPÔSO, CATARINA ; DE OLIVEIRA, WILMA HELENA ; THOMÉ, RODOLFO ;

VERINAUD, LIANA ; TOVAR-MOLL, FERNANDA ; PEIXOTO, CHRISTINA ALVES* . Phosphodiesterase-5 inhibition promotes

remyelination by MCP-1/CCR-2 and MMP-9 regulation in a cuprizone-induced demyelination model. Experimental Neurology, v. 275, p.

143-153, 2016. http://dx.doi.org/10.1016/j.expneurol.2015.10.013 *IN COLLABORATION WITH PEIXOTO [AL15]

13. DE SOUZA, THEO LUIZ FERRAZ ; LIMA, SHEILA MARIA BARBOSA DE ; BRAGA, VANESSA L. DE AZEVEDO ; PEABODY,

DAVID S. ; FERREIRA, DAVIS FERNANDES ; BIANCONI, M. LUCIA ; GOMES, ANDRE MARCO DE OLIVEIRA ; SILVA,

JERSON LIMA ; DE OLIVEIRA, ANDRÉA CHEBLE . Charge neutralization as the major factor for the assembly of nucleocapsid-like

particles from C-terminal truncated hepatitis C virus core protein. PeerJ, v. 4, p. e2670, 2016. http://dx.doi.org/10.7717/peerj.2670

14. FACCHINETTI DE CASTRO GIRÃO, LUCIANA ; GONÇALVES DA ROCHA, SURZA LUCIA ; SOBRAL, RICARDO SPOSINA ;

DINIS ANO BOM, ANA PAULA ; FRANCO SAMPAIO, ANDRÉ LUIZ ; GODINHO DA SILVA, JOSÉ ; FERRARA, MARIA

ANTONIETA ; PINTO DA SILVA BON, ELBA ; PERALES, JONAS . Saccharomyces cerevisiae asparaginase II, a potential

antileukemic drug: Purification and characterization of the enzyme expressed in Pichia pastoris. Protein Expression and Purification

(Print), v. 120, p. 118-125, 2016. http://dx.doi.org/10.1016/j.pep.2015.12.012

15. FERREIRA LB ; CATARINA TAVARES ; PESTANA, A. ; PEREIRA, C. L. ; ELOY, C ; PINTO, MT ; CASTRO, P ; BATISTA, R. ;

RIOS, E ; SOBRINHO-SIMOES, M ; GIMBA, ETEL R.P. ; SOARES, P . Osteopontin-a splice variant is overexpressed in papillary

thyroid carcinoma and modulates invasive behavior. OncoTarget, p. 52003-52016, 2016. http://dx.doi.org/10.18632/oncotarget.10468

16. FERREIRA, LUCIANA BUENO ; ELOY, KATARINA ; PESTANA, ANA ; LYRA, JOANA ; MOURA, MARGARIDA ; PRAZERES,

HUGO ; TAVARES, CATARINA ; SOBRINHO-SIMOES, MANUEL ; GIMBA, ETEL RODRIGUES PEREIRA ; SOARES, PAULA .

Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma. European Journal of

Endocrinology, v. 1, p. EJE-15-0577-1, 2016. http://dx.doi.org/10.1530/eje-15-0577

17. FERREIRA, LUCIANA BUENO ; TAVARES, CATARINA ; PESTANA, ANA ; LEITE, CATARINA ; ELOY, CATARINA ; RIOS,

ELISABETE ; CELESTINO, RICARDO ; BATISTA, RUI ; SOBRINHO-SIMOES, MANUEL ; GIMBA, ETEL ; SOARES, PAULA .

Expression of osteopontin isoforms is related with thyroid cancer growth and invasion. Endocrine Abstracts, v. 40, p. 1-1, 2016.

http://dx.doi.org/10.1530/endoabs.40.p4

18. GONÇALVES, KAREN M. ; ITABAIANA, IVALDO ; PAPADIMITRIOU, VASSILIKI ; ZOUMPANIOTI, MARIA ; LEAL, IVANA

C. R. ; DE SOUZA, RODRIGO OCTAVIO MENDONÇA ALVES ; CORDEIRO, YRAIMA ; XENAKIS, ARISTOTELIS .

Nanoencapsulated Lecitase Ultra and lipase, a comparative structural study.. Langmuir, v. 32, p. 6746-6756, 2016.

http://dx.doi.org/10.1021/acs.langmuir.6b00826

19. GUBERT, FERNANDA ; DECOTELLI, ANA B. ; BONACOSSA-PEREIRA, IGOR ; FIGUEIREDO, FERNANDA R. ; ZAVERUCHA-

DO-VALLE, CAMILA ; TOVAR-MOLL, FERNANDA ; HOFFMANN, LUÍSA ; URMENYI, TURAN P. ; SANTIAGO, MARCELO F.

; MENDEZ-OTERO, ROSALIA* . Intraspinal bone-marrow cell therapy at pre- and symptomatic phases in a mouse model of

amyotrophic lateral sclerosis. Stem cell research & therapy, v. 7, p. 1, 2016. http://dx.doi.org/10.1186/s13287-016-0293-4 *IN

COLLABORATION WITH MENDEZ-OTERO [AL 19]

20. LAZAREV, VLADIMIR V. ; DE CARVALHO MONTEIRO, MYRIAM ; VIANNA-BARBOSA, RODRIGO ; DEAZEVEDO,

LEONARDO C. ; LENT, ROBERTO ; TOVAR-MOLL, FERNANDA . Electrophysiological Correlates of Morphological Neuroplasticity

in Human Callosal Dysgenesis. Plos One, v. 11, p. e0152668, 2016. http://dx.doi.org/10.1371/journal.pone.0152668

21. LEMOS, A. E. G. ; DE FREITAS, PP ; FERREIRA LB ; BONAMINO, M ; GIMBA ERP . PCA3 long noncoding RNA modulates the

expression of key cancer-related genes in LNCaP prostate cancer cells. Tumor Biology, 2016. http://dx.doi.org/10.1007/s13277-016-5012-

3

22. MACEDO, BRUNO ; CORDEIRO, YRAIMA ; VENTURA, SALVADOR . Mammalian prion amyloid formation in bacteria. Prion, v.

10, p. 112-118, 2016. http://dx.doi.org/10.1080/19336896.2016.1141859

23. MELO, ADRIANA SUELY DE OLIVEIRA AGUIAR, RENATO SANTANA AMORIM, MELANIA MARIA RAMOS ARRUDA,

MONICA B. MELO, FABIANA DE OLIVEIRA RIBEIRO, SUELEM TAÍS CLEMENTINO BATISTA, ALBA GEAN MEDEIROS

FERREIRA, THALES DOS SANTOS, MAYRA PEREIRA SAMPAIO, VIRGÍNIA VILAR MOURA, SARAH ROGÉRIA MARTINS

RABELLO, LUCIANA PORTELA GONZAGA, CLARISSA EMANUELLE MALINGER, GUSTAVO XIMENES, RENATO DE

OLIVEIRA-SZEJNFELD, PATRICIA SOARES TOVAR-MOLL, FERNANDA CHIMELLI, LEILA SILVEIRA, PAOLA PAZ

DELVECHIO, RODRIGO HIGA, LUIZA CAMPANATI, LORAINE NOGUEIRA, RITA M. R. FILIPPIS, ANA MARIA BISPO

SZEJNFELD, JACOB , et al. ; Congenital Zika Virus Infection. Cadastro do periódico JAMA neurology, v. 1, p. 00, 2016.

http://dx.doi.org/10.1001/jamaneurol.2016.3720

24. MORAES, MARCELA CRISTINA; DA SILVA, FERNANDO DE . Editorial (Thematic Issue : Recent Advances in Cancer Research:

Targets and New Ligands). Current Pharmaceutical Design (Print), v. 22, p. 5885-5886, 2016.

http://dx.doi.org/10.2174/138161282239161214101407

25. NAKAMURA, K. D. M. ; TILLI, T. M. ; WANDERLEY, J. L. ; PALUMBO, A. ; MATTOS, R. M. ; FERREIRA, A. C. ; KLUMB, C. E.

; NASCIUTTI, L. E. ; GIMBA, E. R. . Osteopontin splice variants expression is involved on docetaxel resistance in PC3 prostate cancer

cells. TUMOR BIOLOGY, v. 37, p. 2655-2663, 2016. http://dx.doi.org/10.1007/s13277-015-4095-6

26. OLIVEIRA, E. S. , SOARES, B. L. , LEMOS, S. , ROSA, R. C. A. , RODRIGUES, A. N. , BARBOSA, L. A. , LOPES, D. O. , SANTOS,

L. L. . Screening of the BRCA1 gene in Brazilian patients with breast and/or ovarian cancer via high-resolution melting reaction analysis',

has been accepted for publication in Familial Cancer. Familial Cancer, Artigo Publicado - JCR v. 15, p. 173-181, n. 2016.

http://dx.doi.org/10.1007/s10689-015-9858-0

27. RODRIGUES, MARILI V.N. ; BARBOSA, ALEXANDRE F. ; DA SILVA, JÚLIA F. ; DOS SANTOS, DEBORAH A. ; VANZOLINI,

KENIA L. ; DE MORAES, MARCELA C. ; CORRÊA, ARLENE G. ; CASS, QUEZIA B. . 9-Benzoyl 9-deazaguanines as potent

xanthine oxidase inhibitors. Bioorganic & Medicinal Chemistry (Print), v. 24, p. 226-231, 2016.

http://dx.doi.org/10.1016/j.bmc.2015.12.006

28. SILVA, JERSON L.; CORDEIRO, YRAIMA . The -Jekyll and Hyde- Actions of Nucleic Acids on the Prion-like Aggregation of Proteins.

The Journal of Biological Chemistry (Print), v. 291, p. 15482-15490, 2016. http://dx.doi.org/10.1074/jbc.r116.733428

29. SILVA, LILIAN N. D. , RIBEIRO-NETO, JOSÉ A. , VALADARES, JÉSSICA M. M. , COSTA, MARIANA M. , LIMA, LUCIANA A.

R. S. , GRILLO, LUCIANO A. M. , CORTES, VANESSA F. , SANTOS, HERICA L. , ALVES, STÊNIO N. , BARBOSA, LEANDRO

A. . et al. The Influence of Fatty Acid Methyl Esters (FAMEs) in the Biochemistry and the Na+/K+-ATPase Activity of Culex

quinquefasciatus Larvae. The Journal of Membrane Biology (Print), Artigo Publicado - JCR v. 249, p. 459-467, n. 2016.

http://dx.doi.org/10.1007/s00232-016-9886-1

30. SOARES DE OLIVEIRA-SZEJNFELD, PATRICIA ; LEVINE, DEBORAH ; MELO, ADRIANA SUELY DE OLIVEIRA ; AMORIM,

MELANIA MARIA RAMOS ; BATISTA, ALBA GEAN M. ; CHIMELLI, LEILA ; TANURI, AMILCAR ; AGUIAR, RENATO

SANTANA ; MALINGER, GUSTAVO ; XIMENES, RENATO ; ROBERTSON, RICHARD ; SZEJNFELD, JACOB ; TOVAR-MOLL,

FERNANDA . Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally.

Radiology, v. 281, p. 161584, 2016. http://dx.doi.org/10.1148/radiol.2016161584


1. ACQUARONE, MARIANA ; DE MELO, THIAGO M. ; MEIRELES, FERNANDA ; BRITO-MOREIRA, JORDANO ; OLIVEIRA,

GABRIEL ; FERREIRA, SERGIO T. ; CASTRO, NEWTON G. ; TOVAR-MOLL, FERNANDA ; HOUZEL, JEAN-CHRISTOPHE ;

http://dx.doi.org/10.1080/13554794.2016.1186199

http://dx.doi.org/10.1186/s13104-016-1843-7

http://dx.doi.org/10.1016/j.expneurol.2015.10.013

http://dx.doi.org/10.7717/peerj.2670

http://dx.doi.org/10.1016/j.pep.2015.12.012

http://dx.doi.org/10.18632/oncotarget.10468

http://dx.doi.org/10.1530/eje-15-0577

http://dx.doi.org/10.1530/endoabs.40.p4

http://dx.doi.org/10.1021/acs.langmuir.6b00826

http://dx.doi.org/10.1186/s13287-016-0293-4

http://dx.doi.org/10.1371/journal.pone.0152668

http://dx.doi.org/10.1007/s13277-016-5012-3

http://dx.doi.org/10.1007/s13277-016-5012-3

http://dx.doi.org/10.1080/19336896.2016.1141859

http://dx.doi.org/10.1001/jamaneurol.2016.3720

http://dx.doi.org/10.2174/138161282239161214101407

http://dx.doi.org/10.1007/s13277-015-4095-6

http://dx.doi.org/10.1007/s10689-015-9858-0


http://dx.doi.org/10.1074/jbc.r116.733428

http://dx.doi.org/10.1007/s00232-016-9886-1

http://dx.doi.org/10.1148/radiol.2016161584


33

REHEN, STEVENS K. . Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse

model of Parkinson?s disease. Frontiers in Cellular Neuroscience, v. 9, p. 1, 2015. http://dx.doi.org/10.3389/fncel.2015.00097

2. ALVES, S. L. G. , FERREIRA, L. G. A. , SANTOS, F , NEVES, L. D. , OLIVEIRA, G. C. , CORTES, V. F. , SALOMÉ, K , BARISON,

A. , SANTOS, F. V. , CENZI, G . et al. γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and

the Na,K-ATPase activity effect. Bioorganic & Medicinal Chemistry (Print), Artigo Publicado - JCR v. 23, p. 4397-4404, n. 2015.


3. BARROSO, SHANA P. C. ; NICO, DIRLEI ; NASCIMENTO, DANIELLE ; SANTOS, ANA CLARA V. ; COUCEIRO, JOSÉ

NELSON S. S. ; BOZZA, FERNANDO A*. ; FERREIRA, ANA M. A. ; FERREIRA, DAVIS F. ; PALATNIK-DE-SOUSA, CLARISA

B. ; SOUZA, THIAGO MORENO L. ; GOMES, ANDRE M. O. ; SILVA, JERSON L. ; OLIVEIRA, ANDRÉA C. . Intranasal

Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice. Plos One, v. 10, p. e0128785,

2015. http://dx.doi.org/10.1371/journal.pone.0128785 *IN COLLABORATION WITH BOZZA [AL 20]

4. BRUNORO, GISELLE VILLA FLOR , CARVALHO, PAULO COSTA , FERREIRA, ANDRÉ TEIXEIRA DA SILVA , PERALES,

JONAS , VALENTE, RICHARD HEMMI , DE MOURA GALLO, CLAUDIA VITÓRIA , Pagnoncelli, Dante , NEVES-FERREIRA,

ANA GISELE DA COSTA . Proteomic profiling of nipple aspirate fluid (NAF): Exploring the complementarity of different peptide

fractionation strategies. Journal of Proteomics (Print), Article Posted - JCR v. 117, p. 86-94, n. 2015.

http://dx.doi.org/10.1016/j.jprot.2015.01.011

5. CABRAL, KATIA M. S. ; RAYMUNDO, DIANA P. ; SILVA, VIVIANE S. ; SAMPAIO, LAURA A. G. ; JOHANSON, LAIZES ;

HILL, LUIS FERNANDO ; ALMEIDA, FABIO C. L*. ; CORDEIRO, YRAIMA ; ALMEIDA, MARCIUS S.* . Biophysical Studies

on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions. Plos One, v. 10, p.

e0137916, 2015. http://dx.doi.org/10.1371/journal.pone.0137916 *IN COLLABORATION WITH ALMEIDA, FCL AND ALMEIDA,

MS [AL3]

6. CABRAL,L.P. , NOGUEIRA, T.A. , BARBOSA, L. A. , CALIL-ELIAS, S. , CASTILHO, S. R. . Adverse reactions to docetaxel: an

active survey. Brazilian Journal of Pharmaceutical Sciences (Online), v. 51, p. 1-9, n. 2015. http://dx.doi.org/10.1590/S1984-

82502015000300007

7. CINO, ELIO A. ; SOARES, IACI N. ; FREITAS, MÔNICA S. ; SILVA, JERSON L. . Backbone resonance assignments of the human

p73 DNA binding domain. Biomolecular NMR Assignments (Print), v. 10, p. 49-51, 2015. http://dx.doi.org/10.1007/s12104-015-9635-x

8. CORDEIRO, YRAIMA.; FERREIRA, N. C. . New Approaches for the Selection and Evaluation of Anti-Prion Organic Compounds.

Mini-Reviews in Medical Chemistry, v. 15, p. 84-92, 2015. http://dx.doi.org/10.2174/1389557515666150227111629

9. COUTINHO, GABRIEL ; DRUMMOND, CLÁUDIA ; DE OLIVEIRA-SOUZA, RICARDO ; MOLL, JORGE ; TOVAR-MOLL,

FERNANDA ; MATTOS, PAULO . Immediate story recall in elderly individuals with memory complaints: how much does it contribute

to memory assessment?. International Psychogeriatrics, v. 1, p. 1-8, 2015. http://dx.doi.org/10.1017/S1041610215000307

10. DE MORAES, MARCELA CRISTINA ; SANTOS, JULIANA BOSCO ; DOS ANJOS, DANIEL MEIRA ; RANGEL, LUCIANA

PEREIRA ; VIEIRA, TUANE CRISTINE RAMOS GONÇALVES ; MOADDEL, RUIN ; DA SILVA, JERSON LIMA . Prion protein-

coated magnetic beads: Synthesis, characterization and development of a new ligands screening method. Journal of Chromatography

(Print), v. 1379, p. 1-8, 2015. http://dx.doi.org/10.1016/j.chroma.2014.12.014

11. DE OLIVEIRA, GUILHERME A. P. ; RANGEL, LUCIANA P ; COSTA, DANIELLY C.F. ; SILVA, JERSON L. . Misfolding,

Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer. Frontiers in Oncology, v. 5, p. 97, 2015.

http://dx.doi.org/10.3389/fonc.2015.00097

12. DE OLIVEIRA, GUILHERME A. P. ; SILVA, JERSON L. . A hypothesis to reconcile the physical and chemical unfolding of proteins.

Proceedings of the National Academy of Sciences of the United States of America, v. 112, p. 201500352-E2775?E2784, 2015.

http://dx.doi.org/10.1073/pnas.1500352112

13. DE OLIVEIRA-SOUZA, RICARDO ; MOLL, JORGE ; TOVAR-MOLL, FERNANDA . Broca’s Aphemia: The Tortuous Story of a

Nonaphasic Nonparalytic Disorder of Speech. Journal of the History of the Neurosciences, v. 25, p. 142-168, 2015.

http://dx.doi.org/10.1080/0964704X.2015.1041346

14. DELMONICO, L. , MOREIRA, A. , FRANCO, M. , ESTEVES, E. , SCHERRER, L. , GALLO, C. V. M. , ORNELLAS, M. H. , ALVES,

G. . CDKN2A (p14ARF/p16INK4a) and ATM promoter methylation in patients with impalpable breast lesions. Human Pathology (Print),

Article Posted - JCR v. 46, p. 1540-1547, n. 2015. http://dx.doi.org/10.1016/j.humpath.2015.06.016. 15. DRUMMOND, CLÁUDIA ; COUTINHO, GABRIEL ; FONSECA, ROCHELE PAZ ; ASSUNÇÃO, NAIMA ; TELDESCHI, ALINA ;

DE OLIVEIRA-SOUZA, RICARDO ; MOLL, JORGE ; TOVAR-MOLL, FERNANDA ; MATTOS, PAULO . Deficits in narrative

discourse elicited by visual stimuli are already present in patients with mild cognitive impairment. Frontiers in Aging Neuroscience, v. 7,

p. 1, 2015. http://dx.doi.org/10.3389/fnagi.2015.00096

16. FIGUEIREDO, C. P. ; FERREIRA, N. C. ; PASSOS, G. F. ; COSTA, R. ; NEVES, F. ; MACHADO, C. S. ; MASCARELLO, A. ;

CHIARADIA-DELATORRE, L. D. ; NEUENFELDT, P. D. ; NUNES, R. J. ; CORDEIRO, YRAIMA. . Toxicological Evaluation of

Anti-Scrapie Trimethoxychalcones and Oxadiazoles. Anais da Academia Brasileira de Ciências (Online), v. 87, p. 1421-1434, 2015.

http://dx.doi.org/10.1590/0001-3765201520140712

17. GARCIA, I. J. P. , KINOSHITA, P. F. , SCAVONE, C. , MIGNACO, J. A. , CORTES, V. F. , BARBOSA, L. A. , LIMA SANTOS,

HÉRICA . Ouabain Modulates the Lipid Composition of Hippocampal Plasma Membranes from Rats with LPS-induced

Neuroinflammation. The Journal of Membrane Biology (Print), Artigo Publicado - JCR v. 248, p. 1191-1198, n. 2015.

http://dx.doi.org/10.1007/s00232-015-9840-7

18. LENT, ROBERTO ; TOVAR-MOLL, FERNANDA . How can development and plasticity contribute to understanding evolution of the

human brain?. Frontiers in Human Neuroscience, v. 9, p. 1, 2015. http://dx.doi.org/10.3389/fnhum.2015.00208

19. LOPES, LUCAS C. ; BARRETO, MARIA T.M. ; GONÇALVES, KAREN M. ; ALVAREZ, HEIDDY M. ; HEREDIA, MONTSERRAT

FORTUNY ; DE SOUZA, RODRIGO OCTAVIO M.A. ; CORDEIRO, YRAIMA ; DARIVA, CLÁUDIO ; FRICKS, ALINI T. . Stability

and structural changes of horseradish peroxidase: Microwave versus conventional heating treatment. Enzyme and Microbial Technology,

v. 69, p. 10-18, 2015. http://dx.doi.org/10.1016/j.enzmictec.2014.11.002

20. MACEDO, BRUNO ; SANTANNA, R. ; NAVARRO, S. ; CORDEIRO, Y. ; VENTURA, S. . Mammalian prion protein (PrP) forms

conformationally different amyloid intracellular aggregates in bacteria. Microbial Cell Factories, v. 14, p. 174, 2015.

http://dx.doi.org/10.1186/s12934-015-0361-y

21. MARINS, THEO F. ; RODRIGUES, ERIKA C. ; ENGEL, ANNEROSE ; HOEFLE, SEBASTIAN ; BASÍLIO, RODRIGO ; LENT,

ROBERTO ; MOLL, JORGE ; TOVAR-MOLL, FERNANDA . Enhancing Motor Network Activity Using Real-Time Functional MRI

Neurofeedback of Left Premotor Cortex. Frontiers in Behavioral Neuroscience, v. 9, p. 1, 2015.

http://dx.doi.org/10.3389/fnbeh.2015.00341

22. MELLO, EDUARDO ARRUDA ; COHEN, LEONARDO G. ; MONTEIRO DOS ANJOS, SARAH ; CONTI, JULIANA ; ANDRADE,

KARINA NOCELO F. ; TOVAR MOLL, FERNANDA ; MARINS, THEO ; FERNANDES, CORINA A. ; RODRIGUES, WALDYR ;

CONFORTO, ADRIANA BASTOS . Increase in Short-Interval Intracortical Facilitation of the Motor Cortex after Low-Frequency

Repetitive Magnetic Stimulation of the Unaffected Hemisphere in the Subacute Phase after Stroke. Neural Plasticity, v. 2015, p. 1-7, 2015.

http://dx.doi.org/10.1155/2015/407320

23. MORAES, MARCELA C. DE; VANZOLINI, KENIA L. ; CARDOSO, CARMEN LUCIA . Cromatografia de bioafinidade na

identificação e caracterização de ligantes. Cromatografia líquida. 1ed.Rio de Janeiro: Elsevier, 2015, v. , p. 299-339. [BOOK

CHAPTER].

24. MUNIZ, L. V. , LACERDA, R. P. , CHAVES, A. L. F. , SOARES, J. M. A. , LEITAO, T. J. , BARBOSA, L. A. , SANTOS, H. B. ,

RIBEIRO, R. I. M. A. . Osteoradionecrosis of the jaw infected with Actinomyces sp: a challenge for clinical practice. Bioscience Journal

(Online), Artigo Publicado - JCR v. 31, p. 296-302, n. 2015. http://dx.doi.org/10.14393/BJ-v31n1a2015-31

25. RODRIGUES, ERIKA ; PARISE, MAUD ; TOVAR-MOLL, FERNANDA ; CUNHA, ALEXANDRE ; ACIOLY, MARCUS .

Recruitment of Contralateral Supplementary Motor Area in Functional Recovery Following Medial Frontal Lobe Surgery: An fMRI Case

Study. Journal of neurological surgery. Part A, Central European neurosurgery, v. 76, p. 508-512, 2015. http://dx.doi.org/10.1055/s-0035-

1558408

26. SILVA, JERSON L. The increasing velocity of S&T in the State of Rio de Janeiro. The Academic Executive Brief, v. 5, p. 14-17, 2015.

http://dx.doi.org/10.3389/fncel.2015.00097





http://dx.doi.org/10.1590/S1984-82502015000300007

http://dx.doi.org/10.1590/S1984-82502015000300007

http://dx.doi.org/10.1007/s12104-015-9635-x

http://dx.doi.org/10.2174/1389557515666150227111629

http://dx.doi.org/10.1017/S1041610215000307

http://dx.doi.org/10.1016/j.chroma.2014.12.014

http://dx.doi.org/10.3389/fonc.2015.00097


http://dx.doi.org/10.1080/0964704X.2015.1041346

http://dx.doi.org/10.1016/j.humpath.2015.06.016

http://dx.doi.org/10.3389/fnagi.2015.00096

http://dx.doi.org/10.1590/0001-3765201520140712

http://dx.doi.org/10.1007/s00232-015-9840-7

http://dx.doi.org/10.3389/fnhum.2015.00208

http://dx.doi.org/10.1016/j.enzmictec.2014.11.002

http://dx.doi.org/10.1186/s12934-015-0361-y

http://dx.doi.org/10.3389/fnbeh.2015.00341

http://dx.doi.org/10.1155/2015/407320

http://dx.doi.org/10.14393/BJ-v31n1a2015-31

http://dx.doi.org/10.1055/s-0035-1558408

http://dx.doi.org/10.1055/s-0035-1558408


34

27. SILVA, JERSON L.; BARROSO, SHANA P. C. ; MENDES, YGARA S. ; DUMARD, CARLOS H. ; SANTOS, PATRICIA S. ;

GOMES, ANDRE M. O. ; OLIVEIRA, ANDRÉA C. . Pressure-Inactivated Virus: A Promising Alternative for Vaccine Production. In:

Kazuyuki Akasaka; Hitoshi Matsuki. (Org.). Subcellular Biochemistry. 1ed.Dordrecht: Springer Netherlands, 2015, v. , p. 301-318.

[BOOK CHAPTER]

28. SOUSA, L. , GARCIA, I. J. P. , COSTA, T. G. , SILVA, L. N. D. E. , RENO, C. O. , OLIVEIRA, E. S. , TILELLI, C. Q. , SANTOS, L.

L. , CORTES, V. F. , SANTOS, H. L. . et al. Effects of iron overload on the activity of Na,K-ATPase and lipid profile of the human

erythrocyte membrane. Plos One, Artigo Publicado - JCR v. 10, p. e0132852-e0132867, n. 2015.

https://doi.org/10.1371/journal.pone.0132852

29. TILLI, TATIANA ; FERREIRA, LUCIANA ; GIMBA, ETEL . Osteopontin-c mediates the upregulation of androgen responsive genes in

LNCaP cells through PI3K/Akt and androgen receptor signaling. Oncology Letters, v. 1, p. 1-6, 2015.

http://dx.doi.org/10.3892/ol.2015.2939

30. TRENTIN-SONODA, MAYRA ; DA SILVA, ROGÉRIO CIRINO ; KMIT, FERNANDA VIEIRA ; ABRAHÃO, MARIANA VIEIRA ;

MONNERAT CAHLI, GUSTAVO ; BRASIL, GUILHERME VISCONDE ; MUZI-FILHO, HUMBERTO ; SILVA, PAULO ANDRÉ ;

TOVAR-MOLL, FERNANDA FREIRE ; VIEYRA, ADALBERTO* ; MEDEI, EMILIANO* ; CARNEIRO-RAMOS, MARCELA

SORELLI . Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice. Plos

One, v. 10, p. e0139350, 2015. http://dx.doi.org/10.1371/journal.pone.0139350 *IN COLLABORATION WITH VIEYRA [AL 17]

AND MEDEI [AL 16]

31. VIEIRA, T. C. R. G. ; SILVA, JERSON L. . Glycosaminoglycans in Prion and Prion-like Diseases. In: G. Legname; G. Giachin. (Org.).

The Prion Phenomena in Neurodegenerative Diseases: New Frontiers in Neuroscience. 1ed.Hauppauge, NY: Nova Science Publishers,

Inc., 2015, v. , p. 67-87. [BOOK CHAPTER]


1. BRUNORO, G. V. F. , FERREIRA, A. T. S. , TRUGILHO, M. R. O. , OLIVEIRA, T. S. , AMENDOLA, L. C. B. , PERALES, J. ,

VALENTE, R. H. , DE MOURA GALLO, C. V. , PAGNONCELLI, D. , NEVES-FERREIRA, A. G. C. . et al. Potential Correlation

between Tumor Aggressiveness and Protein Expression Patterns of Nipple Aspirate Fluid (NAF) Revealed by Gel-Based Proteomic

Analysis. Current Topics in Medicinal Chemistry (Print), Article Posted - JCR v. 14, p. 359-368, n. 2014.

http://dx.doi.org/10.2174/1568026613666131204121854

2. CARVALHO, CARLOS A.M. ; SOUSA, IVANILDO P. ; SILVA, JERSON L. ; OLIVEIRA, ANDRÉA C. ; GONÇALVES, RAFAEL B.

; GOMES, ANDRE M.O. . Inhibition of Mayaro virus infection by bovine lactoferrin. Virology (New York, N.Y. Print), v. 452-453, p.

297-302, 2014. http://dx.doi.org/10.1016/j.virol.2014.01.022

3. CHAVES, A. L. F. , LIMA, P. O. , SOARES, J. M. A. , SANTOS, H. B. , SILVA, A. G. , MUNIZ, L. V. , SANTOS, F. V. , PEREIRA,

M. C. , RIBEIRO, R. I. M. A. , BARBOSA, L. A. . et al. Effects of Digoxin and Na,K-ATPase Immunoexpression on Human Oral

Squamous Carcinomas. Anticancer Research, Artigo Publicado - JCR v. 34, p. 5397-5403, n. 2014 http://dx.doi.org/10.1007/s00784-012-

0784-3

4. CHAVES, J.A.P. ; SANCHEZ-LÓPEZ, CAROLINA ; GOMES, MARIANA P. B. ; SISNANDE, THÁYNA ; MACEDO, BRUNO ;

OLIVEIRA, VANESSA END ; BRAGA, CAROLINA A. C.* ; RANGEL, LUCIANA P. ; SILVA, JERSON L. ; QUINTANAR,

LILIANA ; CORDEIRO, Y. . Biophysical and morphological studies on the dual interaction of non-octarepeat prion protein peptides with

copper and nucleic acids. JBIC. Journal of Biological and Inorganic Chemistry (Internet), v. 19, p. 839-851, 2014.

http://dx.doi.org/10.1007/s00775-014-1115-8 *IN COLLABORATION WITH BRAGA [AL 2]

5. CORDEIRO, YRAIMA ; MACEDO, BRUNO ; SILVA, JERSON L. ; GOMES, MARIANA P. B. . Pathological implications of nucleic

acid interactions with proteins associated with neurodegenerative diseases. Biophysical Reviews, v. 6, p. 97-110, 2014.

http://dx.doi.org/10.1007/s12551-013-0132-0

6. CORDEIRO, YRAIMA.; LIMA, L. M. T. R. . Infravermelho. In: Hugo Verli. (Org.). Bioinformática: da Biologia à Flexibilidade

Moleculares. 1ed.São Paulo: Sociedade Brasileira de Bioquímica e Biologia Molecular, 2014, v. 1, p. 221-235.[BOOK CHAPTER]

7. CORTINES, JULIANA R. ; LIMA, LUÍS MAURICIO T.R. ; MOHANA-BORGES, RONALDO* ; MILLEN, THIAGO DE A. ;

GASPAR, LUCIANE PINTO ; LANMAN, JASON K. ; PREVELIGE, PETER E. ; SILVA, JERSON L. . Structural insights into the

stabilization of the human immunodeficiency virus type 1 capsid protein by the cyclophilin-binding domain and implications on the virus

cycle. Biochimica et Biophysica Acta. Proteins and Proteomics, v. 1854, p. 341-348, 2014. http://dx.doi.org/10.1016/j.bbapap.2014.12.008

*IN COLLABORATION WITH MOHANA-BORGES [AL 3]

8. DE MORAES, MARCELA C.; VANZOLINI, KENIA L. ; CARDOSO, CARMEN L. ; CASS, QUEZIA B. . New trends in LC protein

ligand screening. Journal of Pharmaceutical and Biomedical Analysis (Print), v. 87, p. 155-166, 2014.

http://dx.doi.org/10.1016/j.jpba.2013.07.021

9. FERREIRA, L. C. , RIBEIRO, R. I. M. A. , LEITAO, T. J. , BARBOSA, L. A. , CHAVES, A. L. F. , MUNIZ, L. V. , SANTOS, H. B. ,

SOARES, J. M. A. . Evolução clínica do carcinoma sarcomatoide de Laringe: um relato de caso. Arquivos Catarinenses de Medicina

(Online), v. 42, p. 82-85, n. 2014.

10. FERREIRA, N. C. ; MARQUES, I. ; DA CONCEIÇÃO, W. J. A. ; MACEDO, BRUNO ; MACHADO, C. S. ; MASCARELLO, A. ;

CHIARADIA-DELATORRE, L. D. ; YUNES, R. A. ; NUNES, R. J. ; HUGHSON, A. G. ; RAYMOND, L. D. ; PASCUTTI, P. G*. ;

CAUGHEY, B. ; CORDEIRO, Y. . Anti-Prion Activity of a Panel of Aromatic Chemical Compounds: In Vitro and In Silico Approaches.

Plos One, v. 9, p. e84531, 2014. http://dx.doi.org/10.1371/journal.pone.0084531

11. FURUKAWA, EMI ; BADO, PATRICIA ; TRIPP, GAIL ; MATTOS, PAULO ; WICKENS, JEFF R. ; BRAMATI, IVANEI E. ;

ALSOP, BRENT ; FERREIRA, FERNANDA MEIRELES ; LIMA, DEBORA ; TOVAR-MOLL, FERNANDA ; SERGEANT, JOSEPH

A. ; MOLL, JORGE . Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD. Plos One, v. 9, p.

e89129, 2014. http://dx.doi.org/10.1371/journal.pone.0089129

12. G. C. SANTOS JR , A. C. S. GOES , C. V. DE MOURA GALLO . Chromatin enrichment of histone marks H4Ac and H3K9me3 in TP53

gene domain in breast cells. Biopolymers and Cell, v. 30, p. 197-202, n. 2014. http://dx.doi.org/10.7124/bc.000896

13. GARCIA, CELINA ; DUBOIS, LUIZ ; XAVIER, ANNA ; GERALDO, LUIZ ; DA FONSECA, ANNA CAROLINA ; CORREIA, ANA

; MEIRELLES, FERNANDA ; VENTURA, GRASIELLA ; ROMÃO, LUCIANA ; CANEDO, NATHALIE HENRIQUES ; DE SOUZA,

JORGE ; DE MENEZES, JOÃO RICARDO ; MOURA-NETO, VIVALDO ; TOVAR-MOLL, FERNANDA ; LIMA, FLAVIA REGINA

. The orthotopic xenotransplant of human glioblastoma successfully recapitulates glioblastoma-microenvironment interactions in a non-

immunosuppressed mouse model. BMC Cancer (Online), v. 14, p. 923, 2014. http://dx.doi.org/10.1186/1471-2407-14-923

14. GONÇALVES, K. M. ; BARBOSA, L. R. S. ; LIMA, L. M. T. R. ; CORTINES, J. R. ; KALUME, D. E. ; Leal, I. C. R. ; Miranda, L. S.

M. ; Souza, R. O. M. A. ; Cordeiro, Yraima. . Conformational dissection of Thermomyces lanuginosus lipase in solution. Biophysical

Chemistry (Print), v. 185, p. 88-97, 2014. http://dx.doi.org/10.1016/j.bpc.2013.12.001

15. LINS-MARTINS, NATÁLIA M. ; YÜCEL, MURAT ; TOVAR-MOLL, FERNANDA ; RODRIGUES, ERIKA C. ; FONTENELLE,

LEONARDO F. . Electroconvulsive Therapy in Obsessive-Compulsive Disorder: A Chart Review and Evaluation of Its Potential

Therapeutic Effects. The Journal of Neuropsychiatry and Clinical Neurosciences (Print), v. 1, p. 1, 2014.

http://dx.doi.org/10.1176/appi.neuropsych.13080184

16. MAIA, G. A. S. , CORTES, V. F. , RIBEIRO, R. I. M. A. , MIGNACO, J. A. , SANTOS, H. L. , FONTES, C. F. L. , BARBOSA, L. A. .

Could Na,K-ATPase play a role in potassium leakage from irradiated erythrocytes?. Clinica Chimica Acta (Print), Artigo Publicado - JCR

v. 433, p. 58-61, n. 2014. http://dx.doi.org/10.1016/j.cca.2014.02.025

17. MALAVASI, N.V. ; CORDEIRO, Y. ; RODRIGUES, D. ; CHURA-CHAMBI, R.M. ; LEMKE, L.S. ; MORGANTI, L. . The effect of

temperature on protein refolding at high pressure: Enhanced green fluorescent protein as a model. Process Biochemistry (1991), v. 49, p.

54-60, 2014. http://dx.doi.org/10.1016/j.procbio.2013.09.022

18. MESENTIER-LOURO, LOUISE ALESSANDRA ; ZAVERUCHA-DO-VALLE, CAMILA ; DA SILVA-JUNIOR, ALMIR JORDÃO ;

NASCIMENTO-DOS-SANTOS, GABRIEL ; GUBERT, FERNANDA ; DE FIGUEIRÊDO, ANA BEATRIZ PADILHA ; TORRES,

ANA LUIZA ; PAREDES, BRUNO D. ; TEIXEIRA, CAMILA ; TOVAR-MOLL, FERNANDA ; MENDEZ-OTERO, ROSALIA* ;

https://doi.org/10.1371/journal.pone.0132852

http://dx.doi.org/10.3892/ol.2015.2939


http://dx.doi.org/10.2174/1568026613666131204121854

http://dx.doi.org/10.1016/j.virol.2014.01.022

http://dx.doi.org/10.1007/s00784-012-0784-3

http://dx.doi.org/10.1007/s00784-012-0784-3

http://dx.doi.org/10.1007/s00775-014-1115-8

http://dx.doi.org/10.1007/s12551-013-0132-0


http://dx.doi.org/10.1016/j.jpba.2013.07.021



http://dx.doi.org/10.7124/bc.000896

http://dx.doi.org/10.1186/1471-2407-14-923

http://dx.doi.org/10.1016/j.bpc.2013.12.001

http://dx.doi.org/10.1176/appi.neuropsych.13080184

http://dx.doi.org/10.1016/j.cca.2014.02.025

http://dx.doi.org/10.1016/j.procbio.2013.09.022


35

SANTIAGO, MARCELO F. . Distribution of Mesenchymal Stem Cells and Effects on Neuronal Survival and Axon Regeneration after

Optic Nerve Crush and Cell Therapy. Plos One, v. 9, p. e110722, 2014. http://dx.doi.org/10.1371/journal.pone.0110722 *IN


19. MORAES, MARCELA CRISTINA DE; TEMPORINI, CATERINA ; CALLERI, ENRICA ; BRUNI, GIOVANNA ; DUCATI,

RODRIGO GAY ; SANTOS, DIÓGENES SANTIAGO ; CARDOSO, CARMEN LUCIA ; CASS, QUEZIABEZERRA ; MASSOLINI,

GABRIELLA . Evaluation of capillary chromatographic supports for immobilized human purine nucleoside phosphorylase in frontal

affinity chromatography studies. Journal of Chromatography (Print), v. 1338, p. 77-84, 2014.


20. NEVES, KLEBER ; FERREIRA, FERNANDA M. ; TOVAR-MOLL, FERNANDA ; GRAVETT, NADINE ; BENNETT, NIGEL C. ;

KASWERA, CONSOLATE ; GILISSEN, EMMANUEL ; MANGER, PAUL R. ; HERCULANO-HOUZEL, SUZANA . Cellular scaling

rules for the brain of afrotherians. Frontiers in Neuroanatomy, v. 8, p. 5, 2014. http://dx.doi.org/10.3389/fnana.2014.00005

21. PEREIRA SOARES, NATHALIA DA COSTA ; TEODORO, ANDERSON JUNGER ; OLIVEIRA, FELIPE LEITE ; TAKIYA,

CHRISTINA MAEDA ; JUNIOR, ANTONIO PALUMBO ; NASCIUTTI, LUIZ EURICO ; LOTSCH, PRISCILA FALAGAN ;

GRANJEIRO, JOSÉ MAURO ; FERREIRA, LUCIANA BUENO ; PEREIRA GIMBA, ETEL RODRIGUES ; BOROJEVIC,

RADOVAN . Lycopene induce apoptosis in human prostate cells and alters the expression of Bax and Bcl-2 genes. Lebensmittel-

Wissenschaft + Technologie / Food Science + Technology, v. 59, p. 1290-1297, 2014. http://dx.doi.org/10.1016/j.lwt.2014.04.028

22. RANGEL, LUCIANA P ; COSTA, DANIELLY CF ; VIEIRA, TUANE CRG ; SILVA, JERSON L . The aggregation of mutant p53

produces prion-like properties in cancer. Prion, v. 8, p. 10.4161/pri.277, 2014. http://dx.doi.org/10.4161/pri.27776

23. ROCHA, S. C. , PESSA, M. T. C. , NEVES, L. D. , ALVES, S. L. G. , SILVA, L. M. , SANTOS, H. L. , OLIVEIRA, S. M. , TARANTO,

A. , COMAR, M. , SILVA, I. V. . et al. 21-Benzylidene Digoxin: A Proapoptotic Cardenolide of Cancer Cells That Up-Regulates Na,K-

ATPase and Epithelial Tight Junctions. Plos One, Artigo Publicado - JCR v. 9, p. e108776-, n. 2014.


24. SANTANNA, R. ; BRAGA, CAROLINA A. C*. A. ; VAREJÃO, N. ; PIMENTA, K. M. ; GRANA-MONTES, R. ; ALVES, A. ;

CORTINES, J. R. ; CORDEIRO, YRAIMA. ; VENTURA, S. ; FOGUEL, DEBORA* . The importance of a gatekeeper residue on the

aggregation of transthyretin: implications to transthyretin-related amyloidoses. The Journal of Biological Chemistry (Print), v. 289, p.

28324-28337, 2014. http://dx.doi.org/10.1074/jbc.m114.563981 *IN COLLABORATION WITH FOGUEL AND BRAGA [AL 2]

25. SANTOS, GILSON C. , DA SILVA, ANA P. A. , FELDMAN, LUCAS , VENTURA, GRASIELLA M. , VASSETZKY, YEGOR , DE

MOURA GALLO, CLAUDIA V. . Epigenetic modifications, chromatin distribution and TP53 transcription in a model of breast cancer

progression. Journal of Cellular Biochemistry (Print), Article Posted - JCR v. 116, p. n/a-n/a, n. 2014. http://dx.doi.org/10.1002/jcb.25003

26. SILVA, JERSON L.; GALLO, CLAUDIA V. DE MOURA ; COSTA, DANIELLY C.F. ; RANGEL, LUCIANA P. . Prion-like

aggregation of mutant p53 in cancer. Trends in Biochemical Sciences (Regular ed.), v. 39, p. 260-267, 2014.

http://dx.doi.org/10.1016/j.tibs.2014.04.001

27. SILVA, JERSON L.; OLIVEIRA, ANDREA C. ; VIEIRA, TUANE C. R. G. ; DE OLIVEIRA, GUILHERME A. P. ; SUAREZ,

MARISA C. ; FOGUEL, DEBORA* . High-Pressure Chemical Biology and Biotechnology. Chemical Reviews, v. 114, p. 7239-7267,

2014. http://dx.doi.org/10.1021/cr400204z *IN COLLABORATION WITH FOGUEL [AL 2]

28. SOUZA, W. F. , BARBOSA, L. A. , LIU, L. , ARAUJO, W. M. , DE-FREITAS-JUNIOR, J. C. M. , FORTUNATO-MIRANDA, N. ,

FONTES, C. F. L. , DIAZ, J. A. M. . Ouabain-Induced Alterations of the Apical Junctional Complex Involve α1 and β1 Na,K-ATPase

Downregulation and ERK1/2 Activation Independent of Caveolae in Colorectal Cancer Cells. The Journal of Membrane Biology (Print),

Artigo Publicado - JCR v. 247, p. 23-33, n. 2014. http://dx.doi.org/10.1007/s00232-013-9607-y

29. TILLI, TATIANA M ; BELLAHCÈNE, AKEILA ; CASTRONOVO, VINCENT ; GIMBA, ETEL R . Changes in the transcriptional

profile in response to overexpression of the osteopontin-c splice isoform in ovarian (OvCar-3) and prostate (PC-3) cancer cell lines. BMC

Cancer (Online), v. 14, p. 433, 2014. http://dx.doi.org/10.1186/1471-2407-14-433

30. TOVAR-MOLL, F.; MONTEIRO, M. ; ANDRADE, J. ; BRAMATI, I. E. ; VIANNA-BARBOSA, R. ; MARINS, T. ; RODRIGUES, E. ;

DANTAS, N. ; BEHRENS, T. E. J. ; DE OLIVEIRA-SOUZA, R. ; MOLL, J. ; LENT, R. . Structural and functional brain rewiring

clarifies preserved interhemispheric transfer in humans born without the corpus callosum. Proceedings of the National Academy of

Sciences of the United States of America (Online), v. 111, p. 7843-7848, 2014. http://dx.doi.org/10.1073/pnas.1400806111

31. TOVAR-MOLL, F; DE OLIVEIRA-SOUZA, RICARDO ; BRAMATI, IVANEI E. ; ZAHN, ROLAND ; CAVANAGH, A. ; TIERNEY,

M. ; MOLL, JORGE ; GRAFMAN, J. . White matter tract damage in the behavioral variant of frontotemporal and corticobasal dementia

syndromes.. Plos One, v. 23, p. e102656, 2014. http://dx.doi.org/10.1371/journal.pone.0102656

32. TOVAR-MOLL, FERNANDA; EVANGELOU, IORDANIS E. ; CHIU, ANNIE W. ; AUH, SUNGYOUNG ; CHEN, CHRISTINA ;

EHRMANTRAUT, MARY ; OHAYON, JOAN M. ; RICHERT, NANCY ; BAGNATO, FRANCESCA . Diffuse and Focal Corticospinal

Tract Disease and Its Impact on Patient Disability in Multiple Sclerosis. Journal of Neuroimaging, v. 1, p. n/a-n/a, 2014.

http://dx.doi.org/10.1111/jon.12171

33. VIEIRA, T. C. R. G. ; CORDEIRO, Y. ; CAUGHEY, B. ; SILVA, J. L. . Heparin binding confers prion stability and impairs its

aggregation. The FASEB Journal, v. 28, p. 2667-2676, 2014. http://dx.doi.org/10.1096/fj.13-246777

34. ZAVERUCHA-DO-VALLE, CAMILA ; MESENTIER-LOURO, LOUISE ; GUBERT, FERNANDA ; MORTARI, NICOLI ; BEATRIZ

PADILHA, ANA ; PAREDES, BRUNO D. ; MENCALHA, ANDRE ; ABDELHAY, ELIANA ; TEIXEIRA, CAMILA ; FERREIRA,

FERNANDA G.M. ; TOVAR-MOLL, FERNANDA ; LOPES DE SOUZA, SERGIO AUGUSTO ; GUTFILEN, BIANCA ; MENDEZ-

OTERO, ROSALIA* ; SANTIAGO, MARCELO F. . Sustained effect of bone marrow mononuclear cell therapy in axonal regeneration

in a model of optic nerve crush. Brain Research, v. 1, p. S0006-8993(14)0, 2014. http://dx.doi.org/10.1016/j.brainres.2014.08.070 *IN



1. BADO, PATRICIA ; ENGEL, ANNEROSE ; DE OLIVEIRA-SOUZA, RICARDO ; BRAMATI, IVANEI E. ; PAIVA, FERNANDO F. ;

BASILIO, RODRIGO ; SATO, JOÃO R. ; TOVAR-MOLL, FERNANDA ; MOLL, JORGE . Functional dissociation of ventral frontal

and dorsomedial default mode network components during resting state and emotional autobiographical recall. Human Brain Mapping

(Print), v. 01, p. n/a-n/a, 2013. http://dx.doi.org/10.1002/hbm.22403

2. BARBOZA, R. B. ; FREITAS, G. R. ; TOVAR-MOLL, F ; FONTENELLE, L. F. . Delayed-onset post-stroke delusional disorder: A case

report. Behavioural Neurology, v. 27, p. 287-291, 2013. http://dx.doi.org/10.3233/BEN-120315

3. BRAGA, CAROLINA A. C. A*. ; CORDEIRO, YRAIMA. . Proteínas: Avaliação da estrutura secundária de proteínas por dicroísmo

circular. In: Monica Montero-Lomeli; Franklin David Rumjanek. (Org.). Técnicas em Biociências - Protocolos Comentados para o

Laboratório. 1ed.Rio de Janeiro: MedBook, 2013, v. 1, p. 59-62. *IN COLLABORATION WITH BRAGA [AL2 ] [BOOK

CHAPTER]

4. CHURA-CHAMBI, R. M. ; CORDEIRO, YRAIMA. ; MALAVASI, N. V. ; LEMKE, L. S. ; RODRIGUES, D. ; MORGANTI, L. . An

analysis of the factors that affect the dissociation of inclusion bodies and the refolding of endostatin under high pressure. Process

Biochemistry (1991), v. 48, p. 250-259, 2013. http://dx.doi.org/10.1016/j.procbio.2012.12.017

5. CORDEIRO, Y.. Proteínas: Avaliação da estrutura secundária de proteínas por infravermelho por transformada de Fourier. In: Monica

Montero-Lomeli; Franklin David Rumjanek. (Org.). Técnicas em Biociências - Protocolos Comentados para o Laboratório. 1ed.Rio de

Janeiro: MedBook, 2013, v. 1, p. 67-72. [BOOK CHAPTER]

6. CORDEIRO, YRAIMA ; FOGUEL, DEBORA* ; SILVA, JERSON L. . Pressure-temperature folding landscape in proteins involved in

neurodegenerative diseases and cancer. Biophysical Chemistry (Print), v. 183, p. 9-18, 2013. http://dx.doi.org/10.1016/j.bpc.2013.06.002

*IN COLLABORATION WITH FOGUEL [AL 2]

7. COUTINHO, GABRIEL ; OLIVEIRA-SOUZA, RICARDO DE ; MOLL, JORGE ; TOVAR-MOLL, FERNANDA ; MATTOS, PAULO .

Is it possible to identify individuals with mild cognitive impairment and Alzheimer's disease using a 30-minute neuropsychological

battery?. Revista de Psiquiatria Clínica (São Paulo. Impresso), v. 40, p. 139-143, 2013. http://dx.doi.org/10.1590/s0101-

60832013000400003



http://dx.doi.org/10.3389/fnana.2014.00005

http://dx.doi.org/10.1016/j.lwt.2014.04.028

http://dx.doi.org/10.4161/pri.27776


http://dx.doi.org/10.1074/jbc.m114.563981

http://dx.doi.org/10.1002/jcb.25003

http://dx.doi.org/10.1016/j.tibs.2014.04.001

http://dx.doi.org/10.1021/cr400204z

http://dx.doi.org/10.1007/s00232-013-9607-y

http://dx.doi.org/10.1186/1471-2407-14-433



http://dx.doi.org/10.1111/jon.12171

http://dx.doi.org/10.1096/fj.13-246777

http://dx.doi.org/10.1016/j.brainres.2014.08.070

http://dx.doi.org/10.1002/hbm.22403

http://dx.doi.org/10.3233/BEN-120315



http://dx.doi.org/10.1590/s0101-60832013000400003

http://dx.doi.org/10.1590/s0101-60832013000400003


36

8. DE OLIVEIRA, G. A. P. ; PEREIRA, E. G. ; FERRETTI, G. D. S. ; VALENTE, A. P*. ; CORDEIRO, Y. ; SILVA, J. L. . Intramolecular

Dynamics within the N-Cap-SH3-SH2 Regulatory Unit of the c-Abl Tyrosine Kinase Reveal Targeting to the Cellular Membrane. The

Journal of Biological Chemistry (Print), v. 288, p. 28331-28345, 2013. http://dx.doi.org/10.1074/jbc.m113.500926 *IN

COLLABORATION WITH VALENTE [AL 3]

9. DE OLIVEIRA, GUILHERME A. P. ; ROCHA, CRISTIANE B. ; MARQUES, MAYRA DE A. ; CORDEIRO, YRAIMA ;

SORENSON, MARTHA M.* ; FOGUEL, DÉBORA* ; SILVA, JERSON L. ; SUAREZ, MARISA C. . Insights into the Intramolecular

Coupling between the N- and C-Domains of Troponin C Derived from High-Pressure, Fluorescence, Nuclear Magnetic Resonance, and

Small-Angle X-ray Scattering Studies. Biochemistry (Easton), v. 52, p. 28-40, 2013. http://dx.doi.org/10.1021/bi301139d *IN

COLLABORATION WITH SORENSON AND FOGUEL [AL 2]

10. DUMARD, CARLOS H. ; BARROSO, SHANA P. C. ; DE OLIVEIRA, GUILHERME A. P. ; CARVALHO, CARLOS A. M. ; GOMES,

ANDRE M. O. ; COUCEIRO, JOSÉ NELSON S. S. ; FERREIRA, DAVIS F. ; NICO, DIRLEI ; OLIVEIRA, ANDREA C. ; SILVA,

JERSON L. ; SANTOS, PATRÍCIA S. . Full Inactivation of Human Influenza Virus by High Hydrostatic Pressure Preserves Virus

Structure and Membrane Fusion While Conferring Protection to Mice against Infection. Plos One, v. 8, p. e80785, 2013.


11. ESPERANTE, SEBASTIÁN ANDRÉS ; NOVAL, MARIA GABRIELA ; ALTIERI, TAMARA ANTONELA ; DE OLIVEIRA,

GUILHERME A. P. ; SILVA, JERSON LIMA ; PRAT-GAY, GONZALO DE . Fine Modulation of the Respiratory Syncytial Virus M2-1

Protein Quaternary Structure by Reversible Zinc Removal from its Cys3-His1 Motif.. Biochemistry (Easton), v. 52, p. 130828122324009-

6779?6789, 2013. http://dx.doi.org/10.1021/bi401029q

12. FACHEL, ANGELA A ; TAHIRA, ANA C ; VILELLA-ARIAS, SANTIAGO A ; MARACAJA-COUTINHO, VINICIUS ; GIMBA,

ETEL RP ; VIGNAL, GISELLE M ; CAMPOS, FRANZ S ; REIS, EDUARDO M ; VERJOVSKI-ALMEIDA, SERGIO . Expression

analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations.

Molecular Cancer, v. 12, p. 140, 2013. http://dx.doi.org/10.1186/1476-4598-12-140

13. FERREIRA, L. C. , RIBEIRO, R. I. M. A. MACIEL, R.I. , LEITÃO, T. J. , BARBOSA, L. A. , CHAVES, ALF , MUNIZ, L V ,

SANTOS, HB , ARANTES, JMS . ?Evolução clínica do carcinoma sarcomatoide de Laringe: um relato de caso. Revista Arquivos

Catarinenses de Medicina, v. 42, p. 82-85, n. 2013.

14. FERREIRA, L. G. A. , SOUSA, B. A. , SANTOS, F. V. , VAROTTI, F. P. , SANTOS, A. A. , BARBOSA, L. A. . In vitro Cytotoxic

Activity of β-chalcogen-substituted Michael-aldol Type Adducts Against Hela and RKO Cell Lines. Journal of Biological Sciences

(Faisalabad), v. 13, p. 628-633, n. 2013. http://dx.doi.org/10.3923/jbs.2013.628.633

15. GIMBA, E.R.; TILLI, T.M. . Human osteopontin splicing isoforms: Known roles, potential clinical applications and activated signaling

pathways. Cancer Letters (Print), v. 331, p. 11-17, 2013. http://dx.doi.org/10.1016/j.canlet.2012.12.003

16. GONÇALVES, KAREN M. ; SUTILI, FELIPE K. ; JÚNIOR, IVALDO I. ; FLORES, MARCELLA C. ;

SOTER'DE'MARIZ'E'MIRANDA, LEANDRO ; LEAL, IVANA C. R. ; CORDEIRO, YRAIMA ; LUQUE, RAFAEL ; DE'SOUZA,

RODRIGO OCTAVIO M. ALVES . A Comprehensive Study on the Activity and Deactivation of Immobilized Lecitase Ultra in

Esterifications of Food Waste Streams to Monoacylglycerols. ChemSusChem (Weinheim. Print), v. 6, p. 872-879, 2013.

http://dx.doi.org/10.1002/cssc.201300026

17. GONCALVES, M. M. P.; SANTOS-REBOUCAS, C.; GALLO, C.V.M.. Genética Essencial . 1. ed. Rio de Janeiro: Editora Guanabara

Koogan, 2013. v. 1. 1p . 308p. [BOOK]

18. IKONOMIDOU, V. N. ; RICHERT, N. D. ; VORTMEYER, A. ; TOVAR-MOLL, F. ; BIELEKOVA, B. ; COOK, N. E. ; DUYN, J. H. ;

BAGNATO, F. . Evolution of tumefactive lesions in multiple sclerosis: A 12-year study with serial imaging in a single patient. Multiple

Sclerosis, v. 19, p. 1539-1543, 2013. http://dx.doi.org/10.1177/1352458513498124

19. ITABAIANA, IVALDO ; SUTILI, FELIPE K. ; LEITE, SELMA G. F. ; GONÇALVES, KAREN M. ; CORDEIRO, YRAIMA ; LEAL,

IVANA C. R. ; MIRANDA, LEANDRO S. M. ; OJEDA, MANUEL ; LUQUE, RAFAEL ; DE SOUZA, RODRIGO O. M. A. .

Continuous flow valorization of fatty acid waste using silica-immobilized lipases. Green Chemistry (Print), v. 15, p. 518-524, 2013.

http://dx.doi.org/10.1039/c2gc36674f

20. ITABAIANA-JR, I. ; GONÇALVES, K.M. ; CORDEIRO, Y.M.L. ; ZOUMPANIOTI, M. ; LEAL, I.C.R. ; MIRANDA, L.S.M. E ; A DE

SOUZA, R.O.M. ; XENAKIS, A. . Kinetics and mechanism of lipase catalyzed monoacylglycerols synthesis. Journal of Molecular

Catalysis. B, Enzymatic (Print), v. 96, p. 34-39, 2013. http://dx.doi.org/10.1016/j.molcatb.2013.06.008

21. MAIA, G. A. S. , RENO, C. O. , MEDINA, J. M. , SILVEIRA, A. B. , MIGNACO, J. A. , ATELLA, G. C. , CORTES, V. F. ,

BARBOSA, L. A. , SANTOS, H. L. . The effect of gamma radiation on the lipid profile of irradiated red blood cells. Annals of

Hematology (Print), Artigo Publicado - JCR v. 93, p. 753-760, n. 2013. http://dx.doi.org/10.1007/s00277-013-1944-5

22. MATOS, A.R. ; COUTINHO-CAMILLO, C.M. ; THULER, LCS ; FONSECA, F.P. ; SOARES, F.A. ; SILVA, E.A. ; GIMBA, E. R. .

Expression analysis of thrombospondin 2 in prostate cancer and benign prostatic hyperplasia. Experimental and Molecular Pathology

(Print), v. 94, p. 438-44, 2013. http://dx.doi.org/10.1016/j.yexmp.2013.02.002

23. MORAES, MARCELA CRISTINA; CARDOSO, CARMEN L. ; CASS, QUEZIA B. . Immobilized purine nucleoside phosphorylase

from Schistosoma mansoni for specific inhibition studies. Analytical and Bioanalytical Chemistry (Print), v. 405, p. 4871-4878, 2013.

http://dx.doi.org/10.1007/s00216-013-6872-7

24. NOGUEIRA, C. M. , SOUSA, L. , CARRANO, ANGELA PEREIRA , BARBOSA, L. A. . Gerenciamento da terapia transfusional para

paciente de transplante hepático com aloanticorpo alta frequência. Revista de Enfermagem do Centro-Oeste Mineiro (RECOM), v. 3, p.

746-751, n. 2013.

25. OLIVEIRA, GISELE CAPANEMA , MAIA, GRAZIELLE APARECIDA S. , CORTES, VANESSA FARIA , LIMA SANTOS, HÉRICA

, MOREIRA, LEONARDO MARMO , Barbosa, Leandro A. . The effect of γ-radiation on the hemoglobin of stored red blood cells: the

involvement of oxidative stress in hemoglobin conformation. Annals of Hematology (Print), Artigo Publicado - JCR p. 899-906, n. 2013.

http://dx.doi.org/10.1007/s00277-013-1719-z

26. PAIVA, F. F. ; OTADUY, M. C. G. ; DE OLIVEIRA-SOUZA, R. ; MOLL, J. ; BRAMATI, I. E. ; OLIVEIRA, L. ; SOUZA, A. S. ;

TOVAR-MOLL, F . Comparison of human brain metabolite levels using 1H MRS at 1.5T and 3.0T. Dementia & Neuropsychologia, v. 7,

p. 216-220, 2013. http://dx.doi.org/10.1590/S1980-57642013DN70200013

27. PEREIRA RANGEL, LUCIANA; WINTER, E ; GAUTHIER, CHARLOTTE ; TERREUX, R. ; CHIARADIA, L.D. ; MASCARELLO,

A. ; NUNES, R.J. ; YUNES, R.A. ; CRECZYNSKI-PASA, TÂNIA BEATRIZ ; MACALOU, S. ; LORENDEAU, D. ; BAUBICHON-

CORTAY, H. ; FERREIRA-PEREIRA, A. ; DI PIETRO, A. . New structure-activity relationships of chalcone inhibitors of breast cancer

resistance protein: polyspecificity toward inhibition and critical substitutions against cytotoxicity. Drug Design, Development and

Therapy, v. 7, p. 1043-1052, 2013. http://dx.doi.org/10.2147/DDDT.S46983 28. PEREIRA, ADRIANA DE FÁTIMA , PEREIRA, LETICIA GONÇALVES RESENDE , BARBOSA, LEANDRO AUGUSTO DE

OLIVEIRA , FIALHO, SÍLVIA LIGÓRIO , PEREIRA, BRUNO GONÇALVES , PATRICIO, PATRÍCIA SANTIAGO DE OLIVEIRA ,

PINTO, FLÁVIA CARMO HORTA , DA SILVA, GISELE RODRIGUES . Efficacy of methotrexate-loaded poly( ε -caprolactone)

implants in Ehrlich solid tumor-bearing mice. Drug Delivery, Artigo Publicado - JCR v. 20, p. 1-12, n. 2013.

http://dx.doi.org/10.3109/10717544.2013.801052

29. SATO, JOÃO R. ; BASILIO, RODRIGO ; PAIVA, FERNANDO F. ; GARRIDO, GRISELDA J. ; BRAMATI, IVANEI E. ; BADO,

PATRICIA ; TOVAR-MOLL, FERNANDA ; ZAHN, ROLAND ; MOLL, JORGE . Real-Time fMRI Pattern Decoding and

Neurofeedback Using FRIEND: An FSL-Integrated BCI Toolbox. Plos One, v. 8, p. e81658, 2013.


30. SILVA, JERSON; RANGEL, LUCIANA ; COSTA, DANIELLY ; CORDEIRO, YRAIMA ; DE MOURA GALLO, CLAUDIA .

Expanding the Prion Concept to Cancer Biology: Dominant-Negative Effect of Aggregates of Mutant p53 Tumor Suppressor. Bioscience

Reports, v. 33, p. 593-603, 2013. http://dx.doi.org/10.1042/bsr20130065

31. SOARES, NATHALIA DA COSTA PEREIRA ; TEODORO, ANDERSON JUNGER ; OLIVEIRA, FELIPE LEITE ; SANTOS,

CARLOS ANTONIO DO NASCIMENTO ; TAKIYA, CHRISTINA MAEDA ; JUNIOR, OSWALDO SABACK ; BIANCO, MARIO ;

JUNIOR, ANTONIO PALUMBO ; NASCIUTTI, LUIZ EURICO ; FERREIRA, LUCIANA BUENO ; GIMBA, ETEL RODRIGUES

PEREIRA ; BOROJEVIC, RADOVAN . Influence of Lycopene on Cell Viability, Cell Cycle, and Apoptosis of Human Prostate Cancer

and Benign Hyperplastic Cells. Nutrition and Cancer, v. 17, p. 130920134131007-10, 2013.

http://dx.doi.org/10.1080/01635581.2013.812225


http://dx.doi.org/10.1021/bi301139d


http://dx.doi.org/10.1021/bi401029q

http://dx.doi.org/10.1186/1476-4598-12-140

http://dx.doi.org/10.3923/jbs.2013.628.633

http://dx.doi.org/10.1016/j.canlet.2012.12.003

http://dx.doi.org/10.1002/cssc.201300026

http://dx.doi.org/10.1177/1352458513498124

http://dx.doi.org/10.1039/c2gc36674f

http://dx.doi.org/10.1016/j.molcatb.2013.06.008

http://dx.doi.org/10.1007/s00277-013-1944-5

http://dx.doi.org/10.1016/j.yexmp.2013.02.002

http://dx.doi.org/10.1007/s00216-013-6872-7

http://dx.doi.org/10.1007/s00277-013-1719-z

http://dx.doi.org/10.1590/S1980-57642013DN70200013

http://dx.doi.org/10.2147/DDDT.S46983

http://dx.doi.org/10.3109/10717544.2013.801052


http://dx.doi.org/10.1042/bsr20130065

http://dx.doi.org/10.1080/01635581.2013.812225


37

32. SOLANO, ANA GABRIELA REIS , FÁTIMA PEREIRA, ADRIANA , PINTO, FLAVIA CARMO HORTA , FERREIRA, LETÍCIA

GONÇALVES RESENDE , OLIVEIRA BARBOSA, LEANDRO AUGUSTO , FIALHO, SILVIA LIGÓRIO , OLIVEIRA PATRICIO,

PATRÍCIA SANTIAGO , SILVA CUNHA, ARMANDO , SILVA, GISELE RODRIGUES , PIANETTI, GÉRSON ANTÔNIO . et al.

Development and Evaluation of Sustained-Release Etoposide-Loaded Poly(ε-Caprolactone) Implants. AAPS PharmSciTech, Artigo

Publicado - JCR v. 14, p. 890-900, n. 2013. http://dx.doi.org/10.1208/s12249-013-9977-6

33. STANKEVICINS, L. , SILVA, A. P. A. , PASSOS, F. V. , FERREIRA, E. S. , RIBEIRO, M. C. M. , DAVID, M. G. , PIRES, E. J. ,

FERREIRA-MACHADO, S. C. , VASSETZKY, YEGOR , ALMEIDA, C. E. , DE MOURA GALLO, CLAUDIA VITORIA . . MiR-34a

is up-regulated in response to low dose, low energy X-ray induced DNA damage in breast cells. Radiation Oncology (Online), Article

Posted - JCR v. 8, p. 231-, n. 2013. http://dx.doi.org/10.1186/1748-717x-8-231

34. VITTO, H. , MENDONÇA, B. S. , ELSETH, K. M. , ONUL, A. , XUE, J. , VESPER, B. J. , GALLO, C. V. M. , RUMJANEK, F. D. ,

PARADISE, W. A. , RADOSEVICH, J. A. . . Part III. Molecular changes induced by high nitric oxide adaptation in human breast cancer

cell line BT-20 (BT-20-HNO): a switch from aerobic to anaerobic metabolism. Tumor Biology, Article Posted - JCR v. 34, p. 403-413, n.

2013. http://dx.doi.org/10.1007/s13277-012-0564-3

35. VITTO, H. , MENDONÇA, B. S. , ELSETH, K. M. , VESPER, B. J. , PORTARI, E. A. , GALLO, C. V. M. , PARADISE, W. A. ,

RUMJANEK, F. D. , RADOSEVICH, J. A. . Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-

HNO) as it relates to human primary breast tumors. Tumor Biology, Article Posted - JCR v. 34, p. 337-347, n. 2013.

http://dx.doi.org/10.1007/s13277-012-0555-4

Patents and processes developed by ALX, from 2013 to 2016: CORREA, R. S. ; BATISTA, A. A. ; GRAMINHA, A. E. ; Cass, Quezia B. ; de Moraes, Marcela Cristina ; COMINETTI, M. R. .

PROCESSO DE OBTENÇÃO DE COMPOSTOS DE RUTÊNIO COM BIOLIGANTES, COMPOSTOS DE RUTÊNIO COM BIOLIGANTES E

SEU USO. 2014, Brasil. Patente: Privilégio de Inovação. Número do registro: BR10201402447, título: "PROCESSO DE OBTENÇÃO DE

COMPOSTOS DE RUTÊNIO COM BIOLIGANTES, COMPOSTOS DE RUTÊNIO COM BIOLIGANTES E SEU USO" , Instituição de registro:

INPI - Instituto Nacional da Propriedade Industrial, Depositante (s): Alzir Azevedo Batista, Depósito: 30/09/2014; Depósito PCT: 30/09/2014.

http://dx.doi.org/10.1208/s12249-013-9977-6

http://dx.doi.org/10.1186/1748-717x-8-231

http://dx.doi.org/10.1007/s13277-012-0564-3

http://dx.doi.org/10.1007/s13277-012-0555-4


38

AL 2 - Associated Laboratory of Structural Biology of

Cardiac and Amyloidogenic Proteins

- Coordinator: Débora Foguel- Instituto de Bioquímica Médica (IBqM/UFRJ)

- Researchers from national institutions: Bruno Kaufmann Robbs – UFF Friburgo

Carolina Braga – Xerém/UFRJ

Fernando Lucas Palhano Soares- IBqM/UFRJ

Marcia Waddington Cruz – HUCFF/UFRJ

Marisa Carvalho Suarez – Xerém /UFRJ

Martha M. Sorenson – IBqM/UFRJ


Leandro T Oliveira (UFRJ)

Priscila Ferreira da Silva (UFRJ)

Ricardo Sant'Anna de Oliveira (UFRJ)


Aline Miyoko Sakaguchi Yamashita

(UFRJ)

Diana Pelizzari (UFRJ)

Luiza Fernandes (UFRJ)

Marcelo Lima Sant´anna (UFRJ)

Rodrigo Requião (UFRJ)

Thyago Rubens Cardim Pires (UFRJ)


Carolina Andrade (UFRJ)

Fernando Guarino (UFRJ)

Frederico Lima-Rosa (UFRJ)

Geisoellen Felicio Araujo (UFF)

Kristian Wessman (UFRJ)

Mariana Nunes Campello (UFRJ)

Suiane da Silva Couto Pereira (UFF)

- Undergraduate students:

Adriano Suisso Lourenço (UFRJ)

Anna Beatriz Wreden (UFRJ)

Caroliny de Sousa Leite (UFRJ)

Diego Pollo Dutra da Silva (UFF)

Fernanda Cardoso Gomes (UFF)

Gabriela Ferraz (UFRJ)

Gabriela Rocha de Araújo (UFRJ)

Jessica Santana de Araújo (UFRJ)

Juliana dos Santos Oliveira (UFRJ)

Leonardo Ramos Pereira (UFF)

Lucas Nicolau de Queiroz (UFF)

Luiza Monnerat Menezes (UFF)

Maryana Tavares de C Ancillotti (UFRJ)

Mirian Kelly. (UFRJ)

Raissa Soares (UFRJ)

- Technicians:

Santiago Francisco da Silva Alonso

We summarized below some of the main

results obtained during the four years’

period covered by this report (2013 to

2016):

Amyloid fibrils

Amyloids are aggregates of insoluble

proteins that become folded into a shape

that allows many copies of that protein to

stick together forming fibrils. In humans, it

is associated with more than 40 different

pathologies among other stimuli.

Oculoleptomeningeal amyloidosis (OA) is a

fatal and untreatable hereditary disease

characterized by the accumulation of

transthyretin (TTR) amyloid within the

central nervous system. The mechanisms

underlying the pathogenesis of OA, and in

particular how amyloid triggers neuronal

damage, are still unknown. Our results

show that TTR fibrils induce the neurotoxic

activation of microglia in vitro and in vivo,

revealing a novel cellular mechanism that

could be involved in the pathogenesis of

OA, and possibly of other vascular amyloid

dementias, because amyloid fibrils formed

from different proteins have been shown to

share common structural features and toxic

mechanisms (Fig. 1). More generally, our

findings indicate that amyloid fibrils

modulate the immune system, especially

microglial cells, thereby contributing to a


39

vicious cycle of neurodegeneration (Azevedo et.al., 2013).

Figure 1: CM from A25T fibrils-activated microglia induce synapse loss in primary cortical neurons. A25T

fibrils or soluble A25T at 1 mM were incubated for 48 h with microglia cells and then CM (Fib A25T CM and

Sol A25T CM) was transferred to primary neurons for 3 h. As controls, we used CM from PBS- or LPS (100

ng/ml)-activated microglia. Cells were fixed and immunostained with antibodies anti-PSD-95 (red) and anti-

synaptophysin (green), and the colocalization (puncta; yellow) of both proteins suggest the presence of a

functional synapse. Images show a representative neuron incubated with (a) PBS CM, (b) Sol A25T CM, (c)

Fib A25T CM, (d) LPS CM. (e) Quantification of colocalization of PSD-95 and synaptophysin (number of

puncta per image). Each experiment was performed in duplicates and 12–20 images were captured, quantified

for colocalization and the mean of all images was plotted for each experiment. Statistical analysis was

performed in three independent experiments using Kruskal–Wallis test and Dunn’s post hoc test, and

***Po0.01 when PBS CM and Agg A25T CM were compared and **Po0.01 when Sol A25T CM and Agg A25T

CM were compared. Scale bars are 25 mm for all panels

Furthermore, wild type transthyretin (TTR)

is responsible for senile systemic

amyloidosis, and more than 100 mutations

in the TTR gene are involved in familial

amyloid polyneuropathy. The TTR 26–57

segment bears many of these aggressive

amyloidogenic mutations as well as the

binding site for heparin. We demonstrate

here that Lys-35 acts as a gatekeeper

residue in TTR, strongly decreasing its

amyloidogenic potential. . In the presence

of heparin, the protective effect of Lys-35 is

kept at neutral pH, where heparin has a

negligible affinity for TTR but is abolished

at mildly acidic pH, where it binds this

region. Overall, we illustrate how TTR is

yet another amyloidogenic protein

exploiting negative design to prevent its

massive aggregation, and we show how

blockage of conserved protective features

by endogenous factors or mutations might

result in increased disease susceptibility.

These findings would open the possibility

of designing new potential therapeutic

agents against TTR-related amyloidosis

(Sant’Anna et.al., 2014).

In another research line, we investigated the

mechanisms of action of Epigallocatechin-

3-gallate (EGCG - the principal polyphenol

present in green tea), towards preventing

aggregation and remodeling mature

amyloid fibrils. We show that EGCG

amyloid remodeling activity in vitro is

dependent on auto-oxidation of the EGCG.

Oxidized and unoxidized EGCG binds to

amyloid fibrils, preventing the binding of

thioflavin T (Fig. 2). Oxidized EGCG

molecules react with free amines within the

amyloid fibril through the formation of


40

Schiff bases, cross-linking the fibrils, which

may prevent dissociation and toxicity, but

these aberrant post-translational

modifications do not appear to be the major

driving force for amyloid remodeling by

EGCG treatment. We hypothesize that

aberrant post-translational modifications

mediated by EGCG treatment appear to

occur collaterally with the hydrophobic

remodeling process that seems to be the

main driver for EGCG amyloid remodeling

(Palhano et.al., 2013).

Figure 2: Amyloid remodeling activity of EGCG

on IAPP fibrils. Mature IAPPAc8−24 (A) amyloid

fibrils (65 mg/mL) were incubated in the absence

or presence of 30 μM EGCG for 24 h at 25 °C.

After the centrifugation/wash protocol, the ThT

fluorescence (B), CD (D), and AFM images (E,F)

were recorded. Insets of panels E and F: each

image is 2 μm × 2 μm. An aliquot of these samples

was boiled or not in 2% SDS and then applied to

FR membrane that was stained by Ponceau (C).

Amyloid fibrils also can induce neutrophils

to release extracellular traps (NETs) of their

chromosomal DNA to trap and kill

microorganisms. The intracellular signaling

involved in NET formation is complex and

remains unclear for most tested stimuli.

Herein we demonstrate that a metabolic

shift toward the pentose phosphate pathway

(PPP) is necessary for NET release because

glucose-6-phosphate dehydrogenase

(G6PD), an important enzyme from PPP,

fuels NADPH oxidase with NADPH to

produce superoxide and thus induce NETs

(Fig. 3). In addition, we observed that

mitochondrial reactive oxygen species,

which are NADPH-independent, are not

effective in producing NETs. These data

shed new light on understanding novel

pathways involved in NET release and how

neutrophil glycolytic metabolism

contributes to NET formation (Azevedo

et.al., 2015).

Figure 3: The pentose phosphate pathway enzyme,

G6PD, is necessary for NET formation. D–G,

neutrophils treated as shown in panel C were

incubated with anti-human elastase (Ela; green),

anti-human MPO (red), and a DNA marker

(Hoechst; blue). D.

The recent CEPARM consolidation in our

university hospital led to the identification

of the rare A19D-TTR variant in a Brazilian

patient, suggesting that other new,

uncharacterized mutants could be identified

in the coming years. We believe that FoldX

could be used as a first tool to probe new

TTR mutants’ stability and consequently

amyloidogenicity (Ferreira et.al., 213).

Proteins involved in muscle contraction

The troponin complex, is formed by three

regulatory proteins (troponin C, troponin I,

and troponin T) that is integral to muscle

contraction. Troponin C (TnC) binds to

calcium ions, playing the main role in Ca2+

dependent regulation of muscle

contraction.in vertebrate skeletal muscle.

TnC consists of two structurally

homologous domains, the N- and C-


41

domains; connected by an exposed α- helix.

Mutants of full-length TnC and of its

isolated domains have been constructed

using site-directed mutagenesis to replace

different Phe residues with Trp. In

summary, we found that the binding of

Ca2+ and Mg2+ to sites III and IV has

opposite effects on the structure of the N-

domain. The thermodynamic stability of the

N-domain increases when Mg2+ is bound

to the C-domain29 and decreases when

sites III and IV are occupied by Ca2+, even

when Ca2+ is bound to sites I and II. In the

presence of Ca2+, we also observed that the

C-domain affects the affinity of the N-

domain for Ca2+ (Fig. 4). This

intramolecular coupling observed between

the N- and C-domains for the isolated TnC

subunit upon the binding of Ca2+ may also

increase the overall stability of the entire

troponin complex (TnC, TnI, and TnT), as

shown by a classical differential scanning

calorimetry study of the isolated cardiac Tn

complex,55 and may trigger muscle

contraction. We also observed, by

construction of lowresolution 3D models

using SAXS data, that the central helix

becomes thinner and likely more rigid and

stable upon Ca2+ binding. These changes

may affect the cross-talk between the N-

and C-domains. The C-domain of TnC

could modulate the muscle contractile

response utilizing fluctuations in Ca2+ and

Mg2+ concentrations, which has been

observed in fatigue and hypoxia, for

example (De Oliveira, et.al., 2013).

Figure 4: SAXS reconstruction models for the apo and Ca2+-bound forms of F29W TnC in the presence or

absence of urea. (A) Ribbon representation of the high-resolution TnC crystal structure (PDB entry 1NCZ)

colored blue (left). Molecular envelope reconstructions of the apo form (gray mesh) superimposed with the

crystal structure of TnC (blue), differing by a 180° vertical rotation (middle) and a 90° horizontal rotation

(right). (B) Ribbon representation of the high-resolution crystal structure of the TnC Ca2+-bound form (PDB

entry 1TCF) colored blue (left). Molecular envelope reconstructions (gray mesh) for the Ca2+-bound state of

F29W TnC as shown in panel A. (C) Molecular envelope reconstruction of the apo form treated with 4 M urea,

showing the unfolding of the C-domain and the retained globular structure of the N-domain (arrowheads). (D)

Molecular envelope reconstruction of the Ca2+-bound state treated with 7 M urea superimposed on the crystal

structure of the Ca2+-bound state. (E) Changes in the molecular envelope diameter in three different regions

of the protein depicted as hypothetical circumferences obtained from the reconstructed models derived from

the GNOM and GASBOR analyses of the I(q) plots. Dotted lines are shown for the apo form, solid lines for the

Ca2+-bound state, and dashed lines for the Ca2+-bound state treated with 7 M urea. The N-domain, central

helix, and C-domain are colored gold, black, and red, respectively.


42

The heart responds to physiological and

pathophysiological stress factors by

increasing its production of nitric oxide

(NO), which reacts with intracellular

glutathione to form S-nitrosoglutathione

(GSNO), a protein S-nitrosylating agent.

Although S-nitrosylation protects some

cardiac proteins against oxidative stress,

direct effects on myofilament performance

are unknown. We hypothesize that S-

nitrosylation of sarcomeric proteins (SPs)

will modulate the performance of cardiac

myofilaments. We observed that specific

physiological effects are associated with S-

nitrosylation of a limited number of

cysteine residues in sarcomeric proteins,

which also offer potential targets for

interventions in pathophysiological

situations. We infer that low levels of S-

nitrosylation initially contribute small

decreases in Ca2+ sensitivity to the down-

regulation of contractile function. As stress

intensifies into the realm of

pathophysiology, sarcomeric protein S-

nitrosylation accumulates and can depress

crossbridge turnover and relaxation.

Nevertheless, these modifications protect

against permanent damage by virtue of their

reversibility (Figueiredo et.al., 2015).

Aggregation of neuronal proteins

Many neurodegenerative diseases are

characterized by the abnormal

accumulation of aggregated proteins in the

brain. Synucleinopathies are a group of

progressive disorders, which includes

Parkinson’s, characterized by the abnormal

aggregation and accumulation of the

neuronal protein α-synuclein (aSyn).

Recently, aSyn pathology was shown to

spread between neurons in a prion-like

manner. Proteins that exhibit self-

propagating capacity appear to be able to

adopt different stable conformational states,

known as protein strains, which can be

modulated both by environmental and by

protein-intrinsic factors. Here, we studied

the effects that different aSyn species have

on neurons using a combination of

neurodegeneration-associated factors: the

H50Q aSyn mutant and the presence of

copper (Fig. 5). Importantly, we

demonstrate that exogenous aSyn promotes

toxicity and inclusion formation, and that

these effects are inversely correlated. Our

data shed light onto the pathological

mechanisms associated with aSyn

aggregation, forming the foundation for

future therapeutic strategies (Villar-Pique

et.al., 2016).

Figure 5: Distribution of exogenous and

endogenous aSyn in the S129 p-aSyn inclusions.

(A) Neuritic (Top), perykarial (Middle), and

nuclear (Bottom) p-aSyn inclusions show partial

or total colocalization with rat-specific aSyn. (B)

Presence and absence of labeled aSyn aggregates

in perykarial and nuclear p-aSyn inclusions. (C)

Confocal live cell imaging of cultures exposed to

labeled aSyn aggregates and infected with a GFP-

expressing lentivirus demonstrating the cellular

distribution of the exogenous species at different

time points after exposure. (Scale bars, 10 μm.)

Protein isoforms in cancer development

The NFAT (nuclear factor of activated T

cells) family of transcription factors is

composed of four calcium-responsive

proteins (NFAT1 to -4). The NFAT2 gene


43

encodes the isoforms NFAT2α and

NFAT2β that result mainly from alternative

initiation exons that provide two different

N-terminal transactivation domains.

Because previous studies have shown

oncogenic potential for NFAT2, this study

emphasized the role of the NFAT2 isoforms

in cell transformation. Our data showed that

NFAT2α has increased expression in

Burkitt lymphoma in comparison to

NFAT2β, suggesting that this specific

isoform could be involved in tumor

formation (Fig. 6). Since NFAT2α and

NFAT2β may play differential roles in

cellular functions, deregulation of isoform

expression could contribute to

tumorigenesis. During cell lineage

differentiation, some transcription factors

can employ positive autoregulatory

mechanisms of one specific isoform to

guarantee high levels of the protein to

enable the maintenance of a differentiated

state. This mechanism might account for

the establishment of lymphocyte activation

committed state through the overexpression

of the NFAT2α protein and might be as

well exploited by tumor cells to induce a

transformed commitment state. Taken

together, our results suggest a novel

regulation of the NFAT proteins through

the alternative usage of initiation exons and

define the NFAT2 transcription factors as

dual regulators of cell transformation.

These findings suggest that the NFAT2α

expression may be a potential therapeutic

target. Since the NFAT2 signaling pathway

seems to be important in several tumors,

specific inhibition of the tumorigenic part

of NFAT2 signaling while maintaining its

tumor-suppressive abilities may be a good

strategy for the treatment of cancer (Lucena

et.al., 2015).

Figure 6: In vivo imaging of tumors for EGFP expression from four representative mice 55 days after

inoculation. The color scale represents fluorescence signal in radiance and ranges from red (minimum of 1.11

x 108 photons/sec/cm2 /sr) to yellow (maximum of 1.85 x 109 photons/sec/cm2 /sr).


1. DE OLIVEIRA, GUILHERME A. P. ; MARQUES, MAYRA DE A. ; CRUZEIRO-SILVA, CAROLINA ; CORDEIRO, YRAIMA* ;

SCHUABB, CAROLINE ; MORAES, ADOLFO H. ; WINTER, ROLAND ; OSCHKINAT, HARTMUT ; FOGUEL, D. ; FREITAS, M.

S. ; SILVA, JERSON L*. . Structural basis for the dissociation of α-synuclein fibrils triggered by pressure perturbation of the

hydrophobic core. Scientific Reports, v. 6, p. 37990, 2016. http://dx.doi.org/10.1038/srep37990 *IN COLLABORATION WITH

CORDEIRO AND SILVA [AL 1]

2. LEDO, J. H. ; AZEVEDO, E. P. ; BECKMAN, D. ; RIBEIRO, F. C. ; SANTOS, L. E. ; RAZOLLI, D. S. ; KINCHESKI, G. C. ; MELO,

H. M. ; BELLIO, M. ; TEIXEIRA, A. L. ; VELLOSO, L. A. ; FOGUEL, D. ; DE FELICE, F. G. ; FERREIRA, S. T. . Cross Talk Between

Brain Innate Immunity and Serotonin Signaling Underlies Depressive-Like Behavior Induced by Alzheimer's Amyloid- Oligomers in

Mice. The Journal of Neuroscience, v. 36, p. 12106-12116, 2016. http://dx.doi.org/10.1523/jneurosci.1269-16.2016

3. MAURER, MATHEW S. ; HANNA, MAZEN ; GROGAN, MARTHA ; DISPENZIERI, ANGELA ; WITTELES, RONALD ;

DRACHMAN, BRIAN ; JUDGE, DANIEL P. ; LENIHAN, DANIEL J. ; GOTTLIEB, STEPHEN S. ; SHAH, SANJIV J. ; STEIDLEY,

D. ERIC ; VENTURA, HECTOR ; MURALI, SRINIVAS ; SILVER, MARC A. ; JACOBY, DANIEL ; FEDSON, SAVITRI ;

HUMMEL, SCOTT L. ; KRISTEN, ARNT V. ; DAMY, THIBAUD ; PLANTÉ-BORDENEUVE, VIOLAINE ; COELHO, TERESA ;

MUNDAYAT, RAJIV ; SUHR, OLE B. ; WADDINGTON CRUZ, MÁRCIA ; RAPEZZI, CLAUDIO . Genotype and Phenotype of

Transthyretin Cardiac Amyloidosis. Journal of the American College of Cardiology (Print), v. 68, p. 161-172, 2016.

http://dx.doi.org/10.1016/j.jacc.2016.03.596

4. MOGNOL, G P ; CARNEIRO, F R G ; ROBBS, B K ; FAGET, D V ; VIOLA, J P B . Cell cycle and apoptosis regulation by NFAT

transcription factors: new roles for an old player. Cell Death & Disease, v. 7, p. e2199, 2016. http://dx.doi.org/10.1038/cddis.2016.97

5. REQUIÃO, RODRIGO D. ; DE SOUZA, HENRIQUE JOSÉ ARAUJO ; ROSSETTO, SILVANA ; DOMITROVIC, TATIANA ;

PALHANO, FERNANDO L. . Increased ribosome density associated to positively charged residues is evident in ribosome profiling

experiments performed in the absence of translation inhibitors. RNA Biology, v. 13, p. 00-00, 2016.

http://dx.doi.org/10.1080/15476286.2016.1172755

6. SANT'ANNA., R., O. ; NAVARRO, SUSANNA ; VENTURA, SALVADOR ; PARAOAN, LUMINITA ; FOGUEL, D. . Amyloid

properties of the leader peptide of variant B cystatin C: implications for Alzheimer and Macular Degeneration. FEBS Letters (Print), v.

590, p. 644-654, 2016. http://dx.doi.org/10.1002/1873-3468.12093

7. VILLAR-PIQUÉ, ANNA ; LOPES DA FONSECA, TOMÁS ; SANT’ANNA, RICARDO ; SZEGÖ, ÉVA MÓNIKA ; FONSECA-

ORNELAS, LUIS ; PINHO, RAQUEL ; CARIJA, ANITA ; GERHARDT, ELLEN ; MASARACCHIA, CATERINA ; ABAD


http://dx.doi.org/10.1523/jneurosci.1269-16.2016


http://dx.doi.org/10.1038/cddis.2016.97

http://dx.doi.org/10.1080/15476286.2016.1172755

http://dx.doi.org/10.1002/1873-3468.12093


44

GONZALEZ, ENRIQUE ; ROSSETTI, GIULIA ; CARLONI, PAOLO ; FERNÁNDEZ, CLAUDIO O. ; FOGUEL, DEBORA ;

MILOSEVIC, IRA ; ZWECKSTETTER, MARKUS ; VENTURA, SALVADOR ; OUTEIRO, TIAGO FLEMING . Environmental and

genetic factors support the dissociation between α-synuclein aggregation and toxicity. Proceedings of the National Academy of Sciences

of the United States of America, v. 113, p. 201606791-E6515, 2016. http://dx.doi.org/10.1073/pnas.1606791113

8. WADDINGTON CRUZ, MÁRCIA; AMASS, LESLIE; KEOHANE, DENIS ; SCHWARTZ, JEFFREY ; LI, HUIHUA ;

GUNDAPANENI, BALARAMA . Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in

transthyretin hereditary amyloid polyneuropathy. Amyloid (Carnforth), v. 1, p. 1-6, 2016.

http://dx.doi.org/10.1080/13506129.2016.1207163

9. WOLFE, GIL I. KAMINSKI, HENRY J. ABAN, INMACULADA B. MINISMAN, GREG KUO, HUI-CHIEN MARX, ALEXANDER

STRÖBEL, PHILIPP MAZIA, CLAUDIO OGER, JOEL CEA, J. GABRIEL HECKMANN, JEANNINE M. EVOLI, AMELIA NIX,

WILFRED CIAFALONI, EMMA ANTONINI, GIOVANNI WITOONPANICH, RAWIPHAN KING, JOHN O. BEYDOUN, SAID R.

CHALK, COLIN H. BARBOI, ALEXANDRU C. AMATO, ANTHONY A. SHAIBANI, AZIZ I. KATIRJI, BASHAR LECKY, BRYAN

R.F. BUCKLEY, CAMILLA , VINCENT, ANGELA DIAS-TOSTA, ELZA YOSHIKAWA, HIROAKI WADDINGTON-CRUZ,

MÁRCIA PULLEY, MICHAEL T. RIVNER, MICHAEL H. KOSTERA-PRUSZCZYK, ANNA PASCUZZI, ROBERT M. JACKSON,

CARLAYNE E. GARCIA RAMOS, GUILLERMO S. VERSCHUUREN, JAN J.G.M. MASSEY, JANICE M. KISSEL, JOHN T.

WERNECK, LINEU C. BENATAR, MICHAEL BAROHN, RICHARD J. TANDAN, RUP MOZAFFAR, TAHSEEN CONWIT, ROBIN

ODENKIRCHEN, JOANNE SONETT, JOSHUA R. JARETZKI, ALFRED NEWSOM-DAVIS, JOHN CUTTER, GARY R. ;

Randomized Trial of Thymectomy in Myasthenia Gravis. New England Journal of Medicine (Print), v. 375, p. 511-522, 2016.

http://dx.doi.org/10.1056/NEJMoa1602489


1. ARAUJO, W. M. ; ROBBS, B.K. ; SOUZA, W. F. ; VIDAL-CABRAL, F. ; VIOLA, JOÃO P.B. ; MORGADO-DIAZ, J. A. . PTEN

Overexpression Cooperates With Lithium to Reduce the Malignancy and to Increase Cell Death by Apoptosis Via PI3K/Akt Suppression

in Colorectal Cancer Cells. Journal of Cellular Biochemistry (Print), v. 117, p. n/a-n/a, 2015. http://dx.doi.org/10.1002/jcb.25294

2. AZEVEDO, ESTEFANIA P. ; ROCHAEL, NATALIA C. ; GUIMARÃES-COSTA, ANDERSON B. ; DE SOUZA-VIEIRA, THIAGO S.

; GANILHO, JULIANA ; SARAIVA, ELVIRA M. ; PALHANO, FERNANDO L. ; FOGUEL, DEBORA . A metabolic shift towards

pentose phosphate pathway is necessary for amyloid fibril- and phorbol 12-myristate 13-acetate -induced neutrophil extracellular trap

(NET) formation. The Journal of Biological Chemistry (Print), v. 290, p. jbc.M115.640094-22183, 2015.


3. BRAGA, R. R. ; ALMEIDA, L ; GUERREIRO, L. H. ; TINOCO, P. ; MIRANDA K ; BRAGA, C. A. ; GADELHA, A.P. ; GARCIA, S. ;

LIMA, L. M. . Molecular confinement of human amylin in lipidic nanoparticles. Journal of Liposome Research, v. 4, p. 1-11, 2015.

http://dx.doi.org/10.3109/08982104.2015.1076462

4. DOMITROVIC, TATIANA ; RAYMUNDO, DIANA P. ; SILVA, T. F. ; PALHANO, F L . Experimental Evidence for a Revision in the

Annotation of Putative Pyridoxamine 5'-Phosphate Oxidases P(N/M)P from Fungi. PLoS One, v. 10, p. e0136761, 2015.


5. ERICZON, BO-GÖRAN ; WILCZEK, HENRYK E. ; LARSSON, MARIE ; WIJAYATUNGA, PRIYANTHA ; STANGOU, ARIE ;

PENA, JOÃO RODRIGUES ; FURTADO, EMANUEL ; BARROSO, EDUARDO ; DANIEL, JORGE ; SAMUEL, DIDIER ; ADAM,

RENE ; KARAM, VINCENT ; POTERUCHA, JOHN ; LEWIS, DAVID ; FERRAZ-NETO, BEN-HUR ; CRUZ, MÁRCIA

WADDINGTON ; MUNAR-QUES, MIGUEL ; FABREGAT, JUAN ; IKEDA, SHU-ICHI ; ANDO, YUKIO ; HEATON, NIGEL ;

OTTO, GERD ; SUHR, OLE . Liver Transplantation for Hereditary Transthyretin Amyloidosis. Transplantation, v. 99, p. 1847-1854,

2015. http://dx.doi.org/10.1097/TP.0000000000000574

6. FIGUEIREDO-FREITAS, CICERO ; DULCE, RAUL ; FOSTER, MATTHEW W ; LIANG, JINGSHENG ; YAMASHITA, ALINE M.S.

; LIMA-ROSA, FREDERICO L ; THOMPSON, WILL J ; MOSELEY, ARTHUR M ; HARE, JOSHUA M ; NOGUEIRA, LEONARDO

; SORENSON, MARTHA M ; PINTO, JOSE RENATO . S-nitrosylation of sarcomeric proteins depresses myofilament Ca2+ sensitivity

in intact cardiomyocytes. Antioxidants & Redox Signaling, v. 23, p. 1-18, 2015. http://dx.doi.org/10.1089/ars.2015.6275

7. GERTZ, MORIE A. ; BENSON, MERRILL D. ; DYCK, PETER J. ; GROGAN, MARTHA ; COELHO, TERRESA ; CRUZ, MARCIA ;

BERK, JOHN L. ; PLANTE-BORDENEUVE, VIOLAINE ; SCHMIDT, HARTMUT H.J. ; MERLINI, GIAMPAOLO . Diagnosis,

Prognosis, and Therapy of Transthyretin Amyloidosis. Journal of the American College of Cardiology (Print), v. 66, p. 2451-2466, 2015.


8. LATGE, CRISTIANE ; CABRAL, KATIA M.S. ; DE OLIVEIRA, GUILHERME A. P. ; RAYMUNDO, DIANA P. ; FREITAS, JULIA

A. ; JOHANSON, LAIZES ; ROMÃO, L. ; PALHANO, FERNANDO L. ; HERRMANN, TORSTEN ; ALMEIDA, MARCIUS S*. ;

FOGUEL, D. . The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its

Neuroprotective Role Against α-Synuclein Oligomers. The Journal of Biological Chemistry (Print), v. 289, p. 28324-28337, 2015.

http://dx.doi.org/10.1074/jbc.m115.662254 *IN COLLABORATION WITH ALMEIDA [AL3]

9. LUCENA, PEDRO I. ; FAGET, DOUGLAS V. ; PACHULEC, E. ; ROBAINA, M. C. ; KLUMB, C. E. ; ROBBS, B.K. ; VIOLA, J. P. D.

B. . NFAT2 isoforms differentially regulate gene expression, cell death and transformation through alternative N-terminal domains.

Molecular and Cellular Biology (Print), v. x, p. MCB.00501-15, 2015. http://dx.doi.org/10.1128/mcb.00501-15

10. OLIVEIRA, LEANDRO T. ; LEON, GABBRIELA V.O. ; PROVANCE, D. WILLIAM ; DE MELLO, FERNANDO G. ; SORENSON,

MARTHA M. ; SALERNO, VERÔNICA P. . Exogenous β-amyloid peptide interferes with GLUT4 localization in neurons. Brain

Research, v. 1615, p. 42-50, 2015. http://dx.doi.org/10.1016/j.brainres.2015.04.026

11. VASCONCELOS, SONIA M.R. ; SORENSON, MARTHA M. ; WATANABE, EDSON H. ; FOGUEL, DEBORA ; PALÁCIOS,

MARISA . Brazilian Science and Research Integrity: Where are We? What Next?. Anais da Academia Brasileira de Ciências (Online), v.

87, p. 1259-1269, 2015. http://dx.doi.org/10.1590/0001-3765201520150165

12. WADDINGTON CRUZ, MÁRCIA; BENSON, MERRIL D. . A Review of Tafamidis for the Treatment of Transthyretin-Related

Amyloidosis. Neurology and Therapy, v. 1, p. 1-19, 2015. http://dx.doi.org/10.1007/s40120-015-0031-3


1. ARAUJO, THA''S L. S. ; BORGES, JULIO CESAR ; RAMOS, CARLOS H. ; MEYER-FERNANDES, JOSÉ ROBERTO ; OLIVEIRA

JÚNIOR, REINALDO S. ; PASCUTTI, PEDRO G*. ; FOGUEL, DEBORA ; PALHANO, FERNANDO L. . Conformational Changes in

Human Hsp70 Induced by High Hydrostatic Pressure Produce Oligomers with ATPase Activity but without Chaperone Activity.

BIOCHEMISTRY, v. 53, p. 2884-2889, 2014. http://dx.doi.org/10.1021/bi500004q

2. BEIRAL, H. J. ; SORENSON, M. M. ; FIGUEIREDO-FREITAS, CICERO ; GALINA, A. ; VIEYRA, A.* . The impact of stem cells on

electron fluxes, proton translocation and ATP synthesis in kidney mitochondria after ischemia/reperfusion. Cell Transplantation, v. 23, p.

207-220, 2014. http://dx.doi.org/10.3727/096368912X659862 *IN COLLABORATION WITH VIEYRA [AL 17]

3. CHAVES, JULIANA A. P. ; SANCHEZ-LÓPEZ, CAROLINA ; GOMES, MARIANA P. B. ; SISNANDE, THÁYNA ; MACEDO,

BRUNO ; OLIVEIRA, VANESSA END ; BRAGA, CAROLINA A. C. ; RANGEL, LUCIANA P. ; SILVA, JERSON L*. ;

QUINTANAR, LILIANA ; CORDEIRO, YRAIMA* . Biophysical and morphological studies on the dual interaction of non-octarepeat

prion protein peptides with copper and nucleic acids. JBIC. Journal of Biological Inorganic Chemistry (Print), v. 19, p. 839-851, 2014.

http://dx.doi.org/10.1007/s00775-014-1115-8 *IN COLLABORATION WITH CORDEIRO AND SILVA [AL 1]

4. COELHO, T. ; CONCEICAO, I. M. ; BARROSO, F. ; CRUZ, MÁRCIA WADDINGTON ; SCHMIDIT, H. H. J. ; ROSAS, G. ;

MANDEL, E. S. ; STEWART, M. ; HUERTAS, P. ; KARAYAL, O. N. . Long term effects of tafamidis treatment on transthyretin

familial amyloid polyneuropathy (TTR-FAP): interin results from the FX1A-303 study. European Journal of Neurology, v. 21, p. 81-81,

2014. http://dx.doi.org/10.1212/WNL.0b013e3182661eb1

5. GREINER, ERIN R. ; KELLY, JEFFERY W. ; PALHANO, FERNANDO L. . Immunoprecipitation of Amyloid Fibrils by the Use of an

Antibody that Recognizes a Generic Epitope Common to Amyloid Fibrils. Plos One, v. 9, p. e105433, 2014.



http://dx.doi.org/10.1080/13506129.2016.1207163

http://dx.doi.org/10.1056/NEJMoa1602489

http://dx.doi.org/10.1002/jcb.25294


http://dx.doi.org/10.3109/08982104.2015.1076462


http://dx.doi.org/10.1097/TP.0000000000000574

http://dx.doi.org/10.1089/ars.2015.6275



http://dx.doi.org/10.1128/mcb.00501-15

http://dx.doi.org/10.1016/j.brainres.2015.04.026

http://dx.doi.org/10.1590/0001-3765201520150165

http://dx.doi.org/10.1007/s40120-015-0031-3

http://dx.doi.org/10.1021/bi500004q

http://dx.doi.org/10.3727/096368912X659862

http://dx.doi.org/10.1007/s00775-014-1115-8

http://dx.doi.org/10.1212/WNL.0b013e3182661eb1



45

6. SANT'ANNA, R. ; BRAGA, C. ; VAREJAO, N. ; PIMENTA, K. M. ; GRANA-MONTES, R. ; ALVES, A. ; CORTINES, J. ;

CORDEIRO, Y*. ; VENTURA, S. ; FOGUEL, D. . The importance of a gatekeeper residue on the aggregation of transthyretin:

implications to transthyretin-related amyloidoses. The Journal of Biological Chemistry (Print), p. 10.1074/jbc.M11, 2014.

http://dx.doi.org/10.1074/jbc.M114.563981 *IN COLLABORATION WITH CORDEIRO [AL 1]

7. SILVA, J. L*. ; OLIVEIRA, ANDREA C. ; VIEIRA, TUANE C. R. G. ; DE OLIVEIRA, GUILHERME A. P. ; SUAREZ, MARISA C. ;

FOGUEL, D. . High-Pressure Chemical Biology and Biotechnology. Chemical Reviews, v. 114, p. 7239-7267, 2014.

http://dx.doi.org/10.1021/cr400204z *IN COLLABORATION WITH SILVA [AL 1]


1. ADAMS, D. ; COELHO, T. ; SUHR, O. ; CONCEICAO, I. ; CRUZ, MÁRCIA WADDINGTON ; SCHIMIDT, H. ; CEHELSKY, J. ;

NOCHUR, S. ; VAISHANAW, A. ; GOLLOB, J. . Interim results from phase II Trial on ALN-TTR02, a novel RNAi Therapeutic for the

treatment of Familial Amyloidotic Polyneurpathy. Journal of the Peripheral Nervous System, v. 18, p. 1-4, 2013.

http://dx.doi.org/10.1111/jns5.12025

2. ANDO, YUKIO ; COELHO, TERESA ; BERK, JOHN L ; CRUZ, MARCIA WADDINGTON ; ERICZON, BO-GÖRAN ; IKEDA,

SHU-ICHI ; LEWIS, W DAVID ; OBICI, LAURA ; PLANTÉ-BORDENEUVE, VIOLAINE ; RAPEZZI, CLAUDIO ; SAID, GERARD

; SALVI, FABRIZIO . Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet Journal of Rare Diseases, v. 8, p.

31, 2013. http://dx.doi.org/10.1186/1750-1172-8-31

3. AZEVEDO, E P ; LEDO, J H ; BARBOSA, G ; SOBRINHO, M ; DINIZ, L ; FONSECA, A C C ; GOMES, F ; ROMÃO, L ; LIMA, F R

S ; PALHANO, F L ; FERREIRA, S T ; FOGUEL, D . Activated microglia mediate synapse loss and short-term memory deficits in a

mouse model of transthyretin-related oculoleptomeningeal amyloidosis. Cell Death & Disease, v. 4, p. e789, 2013.


4. AZEVEDO, E. P. C. ; SILVA, P. ; PALHANO, F L ; CAROLINA A. C. A. BRAGA ; FOGUEL, D. . Transthyretin-related amyloidoses:

A structural and thermodynamic approach.. In: Dali Feng. (Org.). Amyloidosis.. 1ed.: InTech, 2013, v. , p. 113-130. [BOOK CHAPTER]

5. CASALINO, A. ; MONTERO-LOMELI, M. ; PALHANO, F L ; MASUDA, CLAUDIO A. . Dosagem de trealose.. In: Mônica Montero-

Lomeli; Franklin Rumjanek. (Org.). Técnicas em biociências. Protocolos comentados para laboratório.. 1ed.: Medbook, 2013, v. 1, p. 120-

124. [BOOK CHAPTER]

6. COELHO, TERESA ; MAIA, LUIS F. ; SILVA, ANA MARTINS ; CRUZ, MÁRCIA W. ; PLANTÉ-BORDENEUVE, VIOLAINE ;

SUHR, OLE B. ; CONCEIÇAO, ISABEL ; SCHMIDT, HARTMUT H.-J. ; TRIGO, PEDRO ; KELLY, JEFFERY W. ;

LABAUDINIÈRE, RICHARD ; CHAN, JASON ; PACKMAN, JEFF ; GROGAN, DONNA R. . Long-term effects of tafamidis for the

treatment of transthyretin familial amyloid polyneuropathy. Journal of Neurology (Print), v. 22, p. 1-1, 2013.

http://dx.doi.org/10.1007/s00415-013-7051-7

7. CORDEIRO, YRAIMA*; FOGUEL, DEBORA ; SILVA, JERSON L*. . Pressure-temperature folding landscape in proteins involved in

neurodegenerative diseases and cancer. Biophysical Chemistry (Print), v. 183, p. 9-18, 2013. http://dx.doi.org/10.1016/j.bpc.2013.06.002

*IN COLLABORATION WITH CORDEIRO AND SILVA [AL 1]

8. DE OLIVEIRA, GUILHERME A. P. ; ROCHA, CRISTIANE B. ; MARQUES, MAYRA DE A. ; CORDEIRO, YRAIMA* ;

SORENSON, MARTHA M. ; FOGUEL, DÉBORA ; SILVA, JERSON L*. ; SUAREZ, MARISA C. . Insights into the Intramolecular

Coupling between the N- and C-Domains of Troponin C Derived from High-Pressure, Fluorescence, Nuclear Magnetic Resonance, and

Small-Angle X-ray Scattering Studies. Biochemistry (Easton), v. 52, p. 28-40, 2013. http://dx.doi.org/10.1021/bi301139d *IN

COLLABORATION WITH CORDEIRO AND SILVA [AL 1]

9. FERREIRA, PRISCILA ; SANT’ANNA, OLIVEIRA ; VAREJÃO, NATHALIA ; LIMA, CINTHIA ; NOVIS, SHENIA ; BARBOSA,

RENATA V. ; CALDEIRA, CONCY M. ; RUMJANEK, FRANKLIN D. ; VENTURA, SALVADOR ; CRUZ, MARCIA W. ; FOGUEL,

DEBORA . Structure-Based Analysis of A19D, a Variant of Transthyretin Involved in Familial Amyloid Cardiomyopathy. Plos One, v. 8,

p. e82484, 2013. http://dx.doi.org/10.1371/journal.pone.0082484

10. FIGUEIREDO-FREITAS, C. ; NOGUEIRA, LEONARDO ; REYNALDO, D. P. ; VELTRI, T. ; PINTO, J. R. ; SORENSON, MARTHA

. Métodos de detecção e identificação de proteínas S-nitrosiladas. In: Montero-Lomeli, M.; Rumjanek, F.D.. (Org.). Técnicas em

Biociências: Protocolos Comentados para o Laboratório. 1ed.Rio de Janeiro: Medbook Editora Científica Ltda, 2013, v. 1, p. 78-83.

[BOOK CHAPTER]

11. LATGÉ, CRISTIANE ; CABRAL, KÁTIA M. S. ; ALMEIDA, M. S. ; FOGUEL, D. . 1H-, 13C- and 15N-NMR assignment of the N-

terminal domain of human cerebral dopamine neurotrophic factor (CDNF). Biomolecular NMR Assignments (Print), v. 7, p. 101-103,

2013. http://dx.doi.org/10.1007/s12104-012-9388-8

12. MURRAY, AMBER N. ; PALHANO, FERNANDO L. ; BIESCHKE, JAN ; KELLY, JEFFERY W. . Surface adsorption considerations

when working with amyloid fibrils in multiwell plates and Eppendorf tubes. Protein Science (Print), v. 22, p. 1531-1541, 2013.

http://dx.doi.org/10.1002/pro.2339

13. PALHANO, F L; FOGUEL, D . Dosagem in vitro de fibras amiloides através da fluorescencia d atioflavina t.. In: Mônica Montero-

Lomeli; Franklin Rumjanek. (Org.). Técnicas em biociências: Protocolos comentados para laboratório.. 1ed.: Medbook, 2013, v. 1, p. 53-

56. [BOOK CHAPTER]

14. PALHANO, F L; FOGUEL, D. . Dosagem de fibras amiloides in vitro através de ligação com vermelho do congo.. In: Mônica Monteiro-

Lomeli; Franklin Rumjanek. (Org.). Técnicas em biociências. Protocolos comentados para laboratório.. 1ed.: Medbook, 2013, v. 1, p. 56-

58. [BOOK CHAPTER]

15. PALHANO, FERNANDO L.; LEE, JIYONG ; GRIMSTER, NEIL P. ; KELLY, JEFFERY W. . Toward the Molecular Mechanism(s) by

Which EGCG Treatment Remodels Mature Amyloid Fibrils. Journal of the American Chemical Society (Print), v. 135, p. 7503-7510,

2013. http://dx.doi.org/10.1021/ja3115696

16. PALMIERI, LEONARDO C. ; MELO-FERREIRA, BRUNO ; BRAGA, CAROLINA A. ; FONTES, GISELLE N. ; MATTOS, LUANA

JOTHA ; LIMA, LUÍS MAURÍCIO T.R. . Stepwise oligomerization of murine amylin and assembly of amyloid fibrils. Biophysical

Chemistry (Print), v. 00, p. 00-00, 2013. http://dx.doi.org/10.1016/j.bpc.2013.07.013

17. ROBBS, BRUNO K.; LUCENA, PEDRO I. ; VIOLA, JOÃO P.B. . The transcription factor NFAT1 induces apoptosis through

cooperation with Ras/Raf/MEK/ERK pathway and upregulation of TNF-α expression. Biochimica et Biophysica Acta. Molecular Cell

Research, v. 1833, p. 2016-2028, 2013. http://dx.doi.org/10.1016/j.bbamcr.2013.04.003

18. SANTANNA, R. ; BRAGA, C. ; POLIKARPOV, I ; VENTURA, S. ; FOGUEL, D. ; Lima, Luis Mauricio T.R. . Inhibition of Human

Transthyretin Aggregation by Non-Steroidal Anti-Inflammatory Compounds: A Structural and Thermodynamic Analysis. International

Journal of Molecular Sciences (Online), v. 14, p. 5284-5311, 2013. http://dx.doi.org/10.3390/ijms14035284

19. SOUZA, W. F.; MIRANDA, N. F. ; ROBBS, B. K. ; ARAUJO, W. M. ; DE-FREITAS-JUNIOR, J. C. ; BASTOS, L. G. ; VIOLA, J. P. B.

; MORGADO-DIAZ, J. A. . Claudin-3 Overexpression Increases the Malignant Potential of Colorectal Cancer Cells: Roles of ERK1/2

and PI3K-Akt as Modulators of EGFR signaling. Plos One, v. 8, p. e74994, 2013. http://dx.doi.org/10.1371/journal.pone.0074994


http://dx.doi.org/10.1021/cr400204z

http://dx.doi.org/10.1111/jns5.12025

http://dx.doi.org/10.1186/1750-1172-8-31


http://dx.doi.org/10.1007/s00415-013-7051-7


http://dx.doi.org/10.1021/bi301139d


http://dx.doi.org/10.1007/s12104-012-9388-8

http://dx.doi.org/10.1002/pro.2339

http://dx.doi.org/10.1021/ja3115696


http://dx.doi.org/10.1016/j.bbamcr.2013.04.003

http://dx.doi.org/10.3390/ijms14035284



46

AL 3 - Associated Laboratory of Proteins Structure

Determination by NMR

- Coordinator:

Fábio Almeida - Instituto de Bioquímica Médica (IBqM/UFRJ) - Centro Nacional de

Ressonância Magnética Nuclear Jiri Jonas (CNRMN)

- Researchers from national institutions:

Ana Paula Valente – IBqM/UFRJ

José Ricardo M. Pires – IBqM/UFRJ

Marcius S. Almeida – IBqM/UFRJ

Ronaldo Mohana Borges – IBCCF/UFRJ

- Collaborators from international institutions:

Dmitry Korzhnev - University of Connecticut Health Center


Anwar Iqbal (UFRJ)

Camila Sousa Campos (UFRJ)

Janaina Figueira Mansur (UFRJ)

Kátia Maria dos Santos Cabral (UFRJ)

Maria Morando (UFRJ)

Talita Duarte Pagani (UFRJ)


Diana Pelizzari Raymundo (UFRJ)

Diego Rodrigues Coelho (UFRJ)

Estefania Anahí Aguilera (UFRJ)

Éverton D'Andrea (UFRJ)

Glauce Moreno Barbosa (UFRJ)

Guilherme Caldas de Andrade (UFRJ)

Leonardo Bartkevihi Di Piero (UFRJ)

Leonardo Vazquez (UFRJ)

Rachel Santos de Menezes (UFRJ)

Ramon Pinheiro Aguiar (UFRJ)

Talita Stelling de Araújo (UFRJ)

Vitor dos Santos Almeida (UFRJ)


Laura Alves Gomes Sampaio (UFRJ)

Mariana Juliani do Amaral (UFRJ)

Nathane Cunha Mebus (UFRJ)

Thaís Cristtina Neves Martins (UFRJ)


Daniele Cristina Passos da Rocha (UEZO)

Douglas Fernandes (UFRJ)

Gabriela Camara (UFRJ)

Joice Lima Menezes (UEZO)

Nicole Cavalcante (UFRJ)

Orlando Ribeiro (UFRJ)

Pedro Henrique Nascimento Carneiro da

Silva (UFRJ)

Vinicius Guedes (UFRJ)

The Associate Laboratory 3 is directly

related to The National Center of Nuclear

Magnetic Resonance of Macromolecules

(CNRMN) and the use of nuclear magnetic

resonance as a tool to solve structure and

dynamics of biomolecules, probe

interactions and in the development of

biologically active compound. We

summarized below some of the main results

obtained during the four years’ period

covered by this report (2013 to 2016):

Cancer-related proteins

The human SHPRH gene maps to the

chromosomal region 6q24 whose allelic

loss or deletions are observed in many types

of cancer, leading to the hypothesis that this

region may encode putative tumor

suppressor gene(s). In this work, we have

determined NMR structure of the PHD

domain from the ‘minor’ insert region of

human SHPRH (Fig. 1), an E3 ubiquitin

ligase responsible for poly-ubiquitination of

DNA-sliding clamp PCNA and a tentative

ATP-dependent DNA translocase that plays

an important role in error-free branch of

DNA damage tolerance. Here we have

shown with the use of NMR titration

experiments that SHPRH PHD domain

does not bind either K4-metylated or


47

unmodified histone H3 tail, contrary to

what might be anticipated from its amino-

acid composition. Thus, SHPRH PHD

domain may have evolved another function

distinct from reading histone H3

methylation state, or might be involved in

recognition of a different histone

modification (Machado et. al., 2013).

Figure 1 - a Stereo-view of the NMR-derived ensemble of 20 leastenergy structures, and b the backbone

conformation for the leastenergy model of the SHPRH PHD domain (residues 652–716). Zincions and side-

chains of zinc-coordinating residues are shown in green, while the cluster of spatially closed aromatic residues

Y657, F659 and W683 is shown in yellow.

Immunologic molecules / Allergens

Human β-defensins (hBDs) are believed to

function as alarm molecules that stimulate

the adaptive immune system when a threat

is present. We reported the first NMR

analysis of an hBD6 and the recognition by

a putative binding partner, a member of the

chemokine family (Fig. 2). NMR CSP and

a HADDOCK-derived complex structural

model show that the CCR2 peptide binds to

the core domain of hBD6 but does not

interact with the hBD6 C-terminus and we

identified residues essential for the

formation of the hBD6/Nt-CCR2 complex.

Details of β-defensin-receptor recognition

may enable structure-based drug discovery

of novel anticancer agents (De Paula et. al.

2013).

Figure 2 - Docking model of the CCR2

sulfopeptide bound to hBD6. The lowest-energy

structure of the Nt-CCR2/hBD6 complex within

the highest-score HADDOCK is presented. (a)

Surface representation of hBD6 with the residues

showing substantial CSPs upon CCR2 titration,

which is shown in red. CCR2 sulfopeptide residues

are depicted in stick representation. (b) Detailed

view of the CCR2-binding pocket. According to

the HADDOCK-generated model, T21, T22, and

sY26 from the peptide form hydrogen bonds with

F1, F2, D3, E4, Q28, and K29 of hBD6, and the

sY28 forms salt bridges with K5 and R35 of hBD6.

Key residues involved in the interaction are

highlighted.

Another line of research focuses on

sensitization towards Bet v 1, the major

birch pollen allergen, which affects over

100 million allergic patients. In search of

intrinsic properties of Bet v 1, which

account responsible for the high allergenic

potential of the protein, we investigated the

effects of ligandbinding on immunogenic as


48

well as allergenic properties. Our data

confirm that the IgE response towards Bet v

1 is heterogeneous. However, we could

identify hot spots on the allergen, which

seem to be preferred for antibody binding.

Binding of DOC did not change the IgE

epitopes, still the exchange of the ligand-

bound state was reduced. This is indicative

for a more stable interaction of DOC-Bet v

1 with the antibodies. Based on these

findings in combination with the

immunological data, we conclude that

humans are exposed to both forms of Bet v

1, ligand bound and free. Nevertheless, the

ligand-binding property of Bet v 1 seems to

be one of the mechanisms responsible for

the high allergenicity of the protein (Asam,

et al., 2014).

Dengue Virus

Dengue affects millions of people

worldwide. No specific treatment is

currently available, in part due to an

incomplete understanding of the viral

components' interactions with host cellular

structures. We tested dengue virus (DENV)

capsid protein (C) interaction with low- and

very low-density lipoproteins (LDL and

VLDL, respectively) using atomic force

microscopy-based force spectroscopy,

dynamic light scattering, NMR and

computational analysis. Our study shows

that DENV C is able to interact specifically

with VLDL, through the involvement of its

Nterminal region and K+ ions. This study

also suggests the existence of a previously

unknown step on the DENV replication

cycle, with the release of new virions from

an infected cell involving the formation of

LVP as a nanocarrier to ferry the virion out

of the cell, and eventually also contributing

for the entry of the virus into a new target

cell. The inhibition of DENV interaction

with VLDL, by pep14-23 or other

molecules, may constitute the basis for new

therapeutic approaches to this important

human disease (Faustino et al., 2013).

In other paper, we combined bioinformatics

and biophysics to analyze the structure of

pep14-23, a recently designed peptide,

based on a conserved segment of DENV

capsid (C) protein. We show that pep14-23

acquires α- helical conformation upon

binding to negatively charged phospholipid

membranes, displaying an asymmetric

charge distribution structural arrangement.

Structure prediction for the N-terminal

segment reveals four viable homodimer

orientations that alternatively shield or

expose the DENV C hydrophobic pocket

(Fig. 3). Taken together, these findings

suggest a new biological role for the

disordered Nterminal region, which may

function as an autoinhibitory domain

mediating DENV C interaction with its

biological targets (Faustino et al, 2014).

Figure 3 - Predicted tertiary structures for DENV C N-terminal region provide insights to protein function.

(A) Structure of DENV C (residues 21 to 100) determined by NMR (ribbon view; PDB ID: 1R6R). (B) In silico

predictions of DENV C tertiary structure showing four possible orientations for the N-terminal disordered

region (residues 1−20; different conformations colored blue, red, yellow, and green) that fit into the

experimentally determined DENV C homodimer tertiary structure (gray). The blue conformation (blue

shadowed area) is shielding the α2-α2′ region and, in this manner, may autoinhibit DENV C interaction with a

molecular target. This is in clear contrast with the green shadowed open conformers, where the α2-α2′ region

is exposed.


49

Another research topic focuses on detecting

changes in the metabolic profile associated

with Dengue pathogenesis in order to help

identifying markers of prognostic and

diagnostic importance. We applied 1 H

NMR exploratory metabolomics to study

longitudinal changes in plasma metabolites

in a cohort in Recife, Brazil. To gain

statistical power, we used innovative paired

multivariate analyzes to discriminate

individuals with dengue fever (DF; mild)

and dengue hemorrhagic fever (DHF;

severe) presenting primary and secondary

infection and subjects with non-specific

infection (ND). Our results showed that a

decrease in plasma LDL and VLDL

discriminated dengue-infected from ND

subjects and also those subjects with severe

infection presented an even decrease in

lipoproteins concentration when compared

to subjects with mild infection. These

results add to the ongoing discussion that

manipulation of lipid metabolism is crucial

for DENV replication and infection. In

addition, a decrease in plasma glutamine

was characteristic of DENV infection and

disease severity and an increase in plasma

acetate discriminated subjects with DF and

DHF from ND-subjects. Several other

metabolites showed to be altered in DENV

infection and the implications of these

alterations are discussed. We hypothesize

that these changes in plasma metabolome

are suggestive of liver dysfunction and

could provide insights into the underlying

molecular mechanisms of dengue

pathogenesis and could help discriminating

individuals at risk to develop severe

infection and to predict disease outcome

(El-Bacha, et al., 2016).

Diabetes

Metabolomics is an important tool for the

evaluation of the human condition, both in

health or disease. This study analyzed the

salivary components of type I diabetic

children (DM1) under six years of age, to

assess oral health related to diabetes

control, as well as metabolite profiling

using NMR. Partial Least Squared

Discriminant Analysis (PLS-DA) was used

to compare healthy (HG) and uncontrolled

DM1 subjects that demonstrated a

separation between the groups with

classificatory performance of ACC = 0.80,

R 2 = 0.92, Q 2 = 0.02 and for DM1

children with glycemia > 200 mg/dL of

ACC = 0.74, R 2 = 0.91, Q 2 = 0.06. The

metabolites that mostly contributed to the

distinction between the groups in the

loading factor were acetate, n-acetyl-sugar,

lactate and sugar. The univariate analysis

showed a decreased salivary concentration

of succinic acid and increased levels of

lactate, acetate and sucrose in uncontrolled

and DM1 children with glycemia > 200

mg/dL. The present study demonstrates that

the salivary profile of DM1 differs from

that of HG children. It appears that diabetes

status control has an important effect on the

salivary composition, since children with

uncontrolled diabetes showed more saliva

alterations than controlled children (De

Oliveira et al., 2016).

Other proteins of medical relevance

BEX3 (Brain Expressed X–linked protein

3) is a member of a mammal-specific

placental protein family associated with

neurodegeneration, the cell cycle and

cancer. In this study, we structurally

characterized BEX3 using biophysical

experimental data. Small angle X-ray

scattering and atomic force microscopy

revealed that BEX3 forms a specific higher-

order oligomer that is consistent with a

globular molecule. Solution nuclear

magnetic resonance, partial proteinase K

digestion, circular dichroism spectroscopy,

and fluorescence techniques that were

performed on the recombinant protein

indicated that the structure of BEX3 is

composed of approximately 31% α-helix

and 20% β-strand, contains partially folded

regions near the N- and C-termini, and a

core which is proteolysis-resistant around

residues 55–120. The self-oligomerization

of BEX3 has been previously reported in

cell culture and is consistent with our in

vitro data (Cabral, et al., 2015).

Thioredoxins (Trx) are ubiquitous proteins

that are present in all living organisms. It

plays a role in many important biological

processes, including redox signaling.

Although not entirely understood,

thioredoxin plays a central role in humans

and is increasingly linked to medicine

through their response to reactive oxygen

species (ROS). In summary, the present

work provided structural information to

understand the properties of the


50

hydrophobic rearrangement experimented

by yTrx1 upon changes in the water cavity

(Fig. 4). The conformational information

induced by changes in internal hydration is

passed along by a global rearrangement of

the hydrophobic core. The global structural

changes leaded to the partial closing of the

water cavity, at the central lobe B (Iqbal et

al, 2015).

Figure 4 - Comparison of the core residues of the

D24A and wild type yTrx1 in oxidized and

reduced states: the structure as zoomed in the

region that contains the water cavity and the

active site. The representation of the side chains of

the selected residues, Ala/ Asp24, Y26, Ile36,

Ala37 and Ile40 are shown in blue sticks a and c

represents D24A mutant in oxidized state and

reduced state, respectively. b and d represents

wild type yTrx1 in oxidized state and reduced

states, respectively. We used 2I9H and 3F3Q as

the wild type yTrx1 structures.

And lastly, Q4D059 (UniProt accession

number), is an 86-residue protein from

Trypanosoma cruzi, conserved in the

related kinetoplastid parasites Trypanosoma

brucei and Leishmania major. These

pathogens are the causal agents of the

neglected diseases: Chagas, sleeping

sickness and leishmaniases respectively and

had recently their genomes sequenced.

Q4D059 shows low sequence similarity

with mammal proteins and because of its

essentiality demonstrated in T. brucei, it is a

potential target for anti-parasitic drugs. The

11 hypothetical proteins homologous to

Q4D059 are all uncharacterized proteins of

unknown function. Here, the solution

structure of Q4D059 was solved by NMR

and its backbone dynamics was

characterized by 15N relaxation parameters

(Fig 5).

Figure 5 - Solution NMR structure of Q4D059

from T. cruzi. (A) Ensemble of the 20 lowest

energy structures, residues 7–92, in stereo view.

Helical regions and b-strands are colored red and

dark blue respectively, and loops are colored light

blue. (B) Ribbon representation of Q4D059 lowest

energy structure. Coloring code is the same as in

A. Side chains of residues with large chemical

shifts deviation from expected values, as well as

spatially close aromatic side chains, are shown and

labeled.

Only limited structural similarities were

found in protein structures deposited in the

PDB, therefore functional inferences based

on protein structure information are not

clear. Q4D059 adopts a a/b fold that is

slightly similar to the ATPase sub-domain

IIB of the heat-shock protein 70 (HSP70)

and to the N-terminal domain of the

ribosomal protein L11.The comparisons

described here can guide the design of

experiments. GST-pulldown and two-

hybrid experiments could provide extra

information about putative interaction

partners, bringing insights into the protein

function. Structural and NMR data

generated in this work will enable ligand-

screening assays.


51

Patents and processes developed by AL3, from 2013 to 2016: ALMEIDA, FÁBIO C.L.; Dapoian, A.T. ; Santos, N.C. ; MARTINS, IVO C. . Denv-derived peptides and methods for the inhibition of the flavivirus

replication. 2013, Brasil.

Register number: BR2012000162. "Denv-derived peptides and methods for the inhibition of the flavivirus replication". INPI - Instituto Nacional da

Propriedade Industrial. 18/07/2013.


1. CABRERA-MUÑOZ, AYMARA ; ROJAS, LARITZA ; GIL, DAYROM F. ; GONZÁLEZ-GONZÁLEZ, YAMILE ; MANSUR,

MANUEL ; CAMEJO, AYAMEY ; Pires, José R. ; ALONSO-DEL-RIVERO ANTIGUA, MADAY . Heterologous expression of

Cenchritis muricatus protease inhibitor II (CmPI-II) in Pichia pastoris system: Purification, isotopic labeling and preliminary

characterization. Protein Expression and Purification (Print), v. 126, p. 127-136, 2016. http://dx.doi.org/10.1016/j.pep.2016.06.011

2. D’ ; DIEHL, ANNE ; SCHMIEDER, PETER ; OSCHKINAT, HARTMUT ; PIRES, JOSÉ RICARDO . Chemical shift assignments and

secondary structure prediction for Q4DY78, a conserved kinetoplastid-specific protein from Trypanosoma cruzi. Biomolecular NMR

Assignments (Print), v. 10, p. 325-328, 2016. http://dx.doi.org/10.1007/s12104-016-9693-8

3. DE OLIVEIRA, LIVIA ROBERTA PIEDADE ; MARTINS, CARLA ; FIDALGO, TATIANA KELLY SILVA ; FREITAS-

FERNANDES, LIANA BASTOS ; DE OLIVEIRA TORRES, RAFAELA ; SOARES, ALINE LAIGNIER ; ALMEIDA, FABIO C.L. ;

VALENTE, Ana Paula ; DE SOUZA, IVETE POMARICO RIBEIRO . Salivary metabolite fingerprint of type 1 diabetes in young

children. Journal of Proteome Research (Print), v. 01, p. 01-01, 2016. http://dx.doi.org/10.1021/acs.jproteome.6b00007

4. EL-BACHA, TATIANA ; STRUCHINER, CLAUDIO J. ; CORDEIRO, MARLI TENORIO ; ALMEIDA, FABIO C. L. ; DE AZEVEDO

MARQUES, ERNESTO TORRES ; DA POIAN, ANDREA T. . 1 H NMR metabolomics of plasma unveils liver dysfunction in dengue

patients. Journal of Virology (Print), v. 01, p. JVI.00187-16-01, 2016. http://dx.doi.org/10.1128/jvi.00187-16

5. EL-BACHA, TATIANA ; STRUCHINER, CLAUDIO J. ; CORDEIRO, MARLI TENORIO ; ALMEIDA, F. C. L. ; DE AZEVEDO

MARQUES, ERNESTO TORRES ; DA POIAN, A. T. . 1 H NMR metabolomics of plasma unveils liver dysfunction in dengue patients.

Journal of Virology (Print), v. 90, p. JVI.00187-16, 2016. http://dx.doi.org/10.1128/jvi.00187-16

6. ERTHAL, LUIZA C.S. ; MARQUES, ADRIANA F. ; ALMEIDA, FÁBIO C.L. ; MELO, GUSTAVO L.M. ; CARVALHO, CAMILA M.

; PALMIERI, LEONARDO C. ; CABRAL, KATIA M.S. ; FONTES, GISELLE N. ; LIMA, LUÍS MAURÍCIO T.R. . Regulation of the

assembly and amyloid aggregation of murine amylin by zinc. Biophysical Chemistry (Print), v. 218, p. 58-70, 2016.


7. FREDRIKSSON, JONAS ; DE PAULA, VIVIANE S. ; VALENTE, ANA PAULA ; ALMEIDA, FABIO C.L. ; BILLETER, MARTIN .

DIADECOMP: A new approach to analyze decompositions from projection spectroscopy. Journal of Magnetic Resonance (San Diego,

Calif. 1997: Print), v. 273, p. 1-8, 2016. http://dx.doi.org/10.1016/j.jmr.2016.10.002

8. SILVA, ISABEL CAETANO DE ABREU DA ; CARNEIRO, VITOR COUTINHO ; VICENTINO, AMANDA ROBERTA

REVOREDO ; AGUILERA, ESTEFANIA ANAHI ; MOHANA-BORGES, R. ; THIENGO, SILVANA ; FERNANDEZ, MONICA

AMMON ; FANTAPPIE, M. . The distinct C-terminal acidic domains of HMGB proteins are functionally relevant in Schistosoma

mansoni. International Journal for Parasitology, v. 01, p. 01-10, 2016. http://dx.doi.org/10.1016/j.ijpara.2015.12.007


1. ALLONSO, DIEGO ; ANDRADE, IAMARA S. ; CONDE, JONAS N. ; COELHO, DIEGO R. ; ROCHA, DANIELE C. P. ; DA SILVA,

MANUELA L. ; VENTURA, GUSTAVO T. ; SILVA, EMILIANA M. ; MOHANA-BORGES, RONALDO . Dengue virus NS1 protein

modulates cellular energy metabolism by increasing glyceraldehyde-3-phosphate dehydrogenase activity. Journal of Virology (Print), v.

89, p. 11871-11883, 2015. http://dx.doi.org/10.1128/jvi.01342-15

2. BARDELLI, M. ; LIVOTI, E. ; SIMONELLI, L. ; PEDOTTI, M. ; MORAES, A. ; VALENTE, A. P. ; VARANI, L. . Epitope mapping by

solution NMR spectroscopy. JMR. Journal of Molecular Recognition, v. 28, p. n/a-n/a, 2015. http://dx.doi.org/10.1002/jmr.2454

3. BUBLIN, MERIMA ; KOSTADINOVA, MARIA ; FUCHS, JULIAN E. ; ACKERBAUER, DANIELA ; MORAES, ADOLFO H. ;

ALMEIDA, FABIO C. L. ; LENGGER, NINA ; HAFNER, CHRISTINE ; EBNER, CHRISTOF ; RADAUER, CHRISTIAN ; LIEDL,

KLAUS R. ; VALENTE, Ana Paula ; BREITENEDER, HEIMO . A Cross-Reactive Human Single-Chain Antibody for Detection of

Major Fish Allergens, Parvalbumins, and Identification of a Major IgE-Binding Epitope. Plos One, v. 10, p. e0142625, 2015.


4. CABRAL, KATIA M. S. ; RAYMUNDO, DIANA P. ; SILVA, VIVIANE S. ; SAMPAIO, LAURA A. G. ; JOHANSON, LAIZES ;

HILL, LUIS FERNANDO ; ALMEIDA, FABIO C. L. ; CORDEIRO, YRAIMA* ; ALMEIDA, MARCIUS S. . Biophysical Studies on

BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions. Plos One, v. 10, p.

e0137916, 2015. http://dx.doi.org/10.1371/journal.pone.0137916 IN COLLABORATION WITH CORDEIRO (AL 1)

5. CABRERA-MUÑOZ, AYMARA ; ROJAS, LARITZA ; ALONSO-DEL-RIVERO ANTIGUA, MADAY ; PIRES, JOSÉ RICARDO .

1H, 13C and 15N resonance assignments and secondary structure analysis of CmPI-II, a serine protease inhibitor isolated from marine

snail Cenchritis muricatus. Biomolecular NMR Assignments (Print), v. 10, p. 153-156, 2015. http://dx.doi.org/10.1007/s12104-015-9656-

5

6. IQBAL, ANWAR ; GOMES-NETO, FRANCISCO ; MIYAMOTO, CATARINA AKIKO ; VALENTE, ANA PAULA ; ALMEIDA,

FABIO C.L. . Dissection of the water cavity of yeast Thioredoxin 1: the effect of a hydrophobic residue in the cavity.. Biochemistry

(Easton), v. 1, p. 150401152501000-0, 2015. http://dx.doi.org/10.1021/acs.biochem.5b00082

7. IQBAL, ANWAR ; MORAES, ADOLFO HENRIQUE ; VALENTE, ANA PAULA ; ALMEIDA, FABIO C. L. . Structures of the

reduced and oxidized state of the mutant D24A of yeast thioredoxin 1: insights into the mechanism for the closing of the water cavity.

Journal of Biomolecular NMR, v. 0000, p. 141120111159000, 2015. http://dx.doi.org/10.1007/s10858-015-9996-6

8. LATGE, CRISTIANE ; CABRAL, KATIA M.S. ; DE OLIVEIRA, GUILHERME A. P. ; RAYMUNDO, DIANA P. ; FREITAS, JULIA

A. ; JOHANSON, LAIZES ; ROMÃO, LUCIANA F. ; PALHANO, FERNANDO L. ; HERRMANN, TORSTEN ; ALMEIDA,

MARCIUS S. ; FOGUEL, DEBORA* . The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic

Factor and Its Neuroprotective Role Against α-Synuclein Oligomers. The Journal of Biological Chemistry (Print), v. 1, p.

jbc.M115.662254, 2015. http://dx.doi.org/10.1074/jbc.M115.662254 IN COLLABORATION WITH FOGUEL (AL 2)

9. LÓPEZ-CASTILLA, ARACELYS ; PONS, TIRSO ; PIRES, JOSÉ R. . NMR structure and dynamics of Q4D059, a kinetoplastid-specific

and conserved protein from Trypanosoma cruzi. Journal of Structural Biology (Print), v. 190, p. 11-20, 2015.

http://dx.doi.org/10.1016/j.jsb.2015.02.007

10. MORAES, A. H. ; ASAM, C. ; BATISTA, A. ; ALMEIDA, F. C. L. ; WALLNER, M. ; FERREIRA, F. ; VALENTE, A. P. . 1H, 13C and

15N resonance assignments and second structure information of Fag s 1: Fagales allergen from Fagus sylvatica. Biomolecular NMR

Assignments (Print), v. 10, p. 45-48, 2015. http://dx.doi.org/10.1007/s12104-015-9634-y

11. MORAES, A. H. ; ASAM, C. ; BATISTA, A. ; ALMEIDA, F. C. L. ; WALLNER, M. ; FERREIRA, F. ; VALENTE, ANA PAULA,

ANA P. VALENTE . 1H, 13C and 15N resonance assignments and second structure information of Fag s 1: Fagales allergen from Fagus

sylvatica. Biomolecular NMR Assignments (Print), v. 1, p. 3-4, 2015. http://dx.doi.org/10.1007/s12104-015-9634-y

12. MORAES, ADOLFO H. ; SIMONELLI, LUCA ; PEDOTTI, MATTIA ; ALMEIDA, FABIO C.L. ; VARANI, LUCA ; VALENTE, ANA

P. . NMR investigation of domain III of Dengue virus E protein: antibody binding modulates conformational exchange in the antigen.

Journal of Virology (Online), v. 90, p. JVI.02314-15-1802-11, 2015. http://dx.doi.org/10.1128/jvi.02314-15

13. REZENDE, CARLOS A. ; SAN GIL, ROSANE A. S. ; BORRÉ, LEANDRO B. ; PIRES, JOSÉ RICARDO ; VAISS, VIVIANE S. ;

RESENDE, JACKSON A. L. C. ; LEITÃO, ALEXANDRE A. ; DE ALENCASTRO, RICARDO B. ; LEAL, KATIA Z. . Combining


http://dx.doi.org/10.1007/s12104-016-9693-8

http://dx.doi.org/10.1021/acs.jproteome.6b00007

http://dx.doi.org/10.1128/jvi.00187-16



http://dx.doi.org/10.1016/j.jmr.2016.10.002

http://dx.doi.org/10.1016/j.ijpara.2015.12.007


http://dx.doi.org/10.1002/jmr.2454



http://dx.doi.org/10.1007/s12104-015-9656-5

http://dx.doi.org/10.1007/s12104-015-9656-5

http://dx.doi.org/10.1021/acs.biochem.5b00082

http://dx.doi.org/10.1007/s10858-015-9996-6



http://dx.doi.org/10.1007/s12104-015-9634-y

http://dx.doi.org/10.1007/s12104-015-9634-y



52

Nuclear Magnetic Resonance Spectroscopy and Density Functional Theory Calculations to Characterize Carvedilol Polymorphs. Journal

of Pharmaceutical Sciences, v. xx, p. n/a-n/a, 2015. http://dx.doi.org/10.1002/jps.24641


1. ABRAHIM-VIEIRA, BÁRBARA ; DA COSTA, EMMERSON C. B. ; DE A. AZEVEDO, PEDRO H. R. ; PORTELA, ALINE C. ;

DIAS, LUIZA R. S. ; PINHEIRO, SERGIO ; TANURI, AMILCAR ; CAPACCIA, ANNE M. ; VENTURA, GUSTAVO T. ; MOHANA-

BORGES, RONALDO ; RODRIGUES, CARLOS R. ; DE SOUZA, ALESSANDRA M. T. ; MURI, ESTELA M. F. . Novel isomannide-

based peptide mimetics containing a tartaric acid backbone as serine protease inhibitors. Medicinal Chemistry Research (Print), v. 23, p.

5305-5320, 2014. http://dx.doi.org/10.1007/s00044-014-1058-1

2. ALLONSO, DIEGO ; MENESES, MARCELO D. F. ; FERNANDES, CARLOS A. ; FERREIRA, DAVIS F. ; MOHANA-BORGES,

RONALDO . Assessing Positivity and Circulating Levels of NS1 in Samples from a 2012 Dengue Outbreak in Rio de Janeiro, Brazil. Plos

One, v. 9, p. e113634, 2014. http://dx.doi.org/10.1371/journal.pone.0113634

3. ALMEIDA, F. C. L.; PINHEIRO, A. S. ; FOLLMER, CRISTIAN . Pitfalls associated with the use of Thioflavin-T to monitor anti-

fibrillogenic activity. Bioorganic & Medicinal Chemistry Letters (Print), v. 24, p. 3194-3198, 2014.

http://dx.doi.org/10.1016/j.bmcl.2014.04.072

4. ALMEIDA, F. C. L.; PINHEIRO, A. S. ; ROMÃO, LUCIANA ; CORTINES, JULIANA ; FOLLMER, CRISTIAN . UV-induced

selective oxidation of Met5 to Met-sulfoxide leads to the formation of neurotoxic fibril-incompetent α-synuclein oligomers. Amyloid

(Carnforth), v. 21, p. 1-12, 2014. http://dx.doi.org/10.3109/13506129.2014.912208

5. ASAM, CLAUDIA ; BATISTA, ALINE L. ; MORAES, ADOLFO H. ; DE PAULA, VIVIANE S ; ALMEIDA, FABIO C.L. ; AGLAS,

LORENZ ; KITZMÜLLER, CLAUDIA ; BOHLE, BARBARA ; EBNER, CHRISTOF ; FERREIRA, FATIMA ; WALLNER,

MICHAEL ; VALENTE, ANA PAULA . Bet v 1 - a Trojan horse for small ligands boosting allergic sensitization?. Clinical and

Experimental Allergy (Print), v. 44, p. n/a-n/a, 2014. http://dx.doi.org/10.1111/cea.12361

6. CORTINES, JULIANA R. ; LIMA, LUÍS MAURICIO T.R. ; MOHANA-BORGES, RONALDO ; MILLEN, THIAGO DE A. ;

GASPAR, LUCIANE PINTO ; LANMAN, JASON K. ; PREVELIGE, PETER E. ; SILVA, JERSON L8. . Structural insights into the

stabilization of the human immunodeficiency virus type 1 capsid protein by the cyclophilin-binding domain and implications on the virus

cycle. Biochimica et Biophysica Acta. Proteins and Proteomics, v. 1854, p. 341-348, 2014. http://dx.doi.org/10.1016/j.bbapap.2014.12.008

IN COLLABORATION WITH SILVA (AL 1)

7. CRUZEIRO-SILVA, CAROLINA ; GOMES-NETO, Francisco ; MACHADO, LUCIANA E. S. F. ; MIYAMOTO, CATARINA A. ;

PINHEIRO, ANDERSON S. ; CORREA-PEREIRA, NATALIA ; DE MAGALHÃES, MARIANA T. Q. ; VALENTE, ANA PAULA ;

ALMEIDA, FABIO C. L. . Hydration and Conformational Equilibrium in Yeast Thioredoxin 1: Implication for H + Exchange.

Biochemistry (Easton), v. 53, p. 2890-2902, 2014. http://dx.doi.org/10.1021/bi401542v

8. DE PAULA, V. S. ; POMIN, V. H. ; VALENTE, A. P. . Unique properties of human -defensin 6 (hBD6) and glycosaminoglycan

complex: sandwich-like dimerization and competition with the chemokine receptor 2 (CCR2) binding site. The Journal of Biological

Chemistry (Print), v. 289, p. 22969-22979, 2014. http://dx.doi.org/10.1074/jbc.m114.572529

9. FAUSTINO, ANDRÉ F. ; GUERRA, GABRIELA M. ; HUBER, ROLAND G. ; HOLLMANN, AXEL ; DOMINGUES, MARCO M. ;

BARBOSA, GLAUCE M. ; ENGUITA, FRANCISCO J. ; BOND, PETER J. ; CASTANHO, MIGUEL A. R. B. ; POIAN, ANDREA T.

DA ; ALMEIDA, FABIO C. L. ; SANTOS, NUNO C. ; MARTINS, IVO C. . Understanding Dengue Virus Capsid Protein Disordered N-

Terminus and pep14-23-Based Inhibition. ACS Chemical Biology, v. 10, p. 141120111159000-526, 2014.

http://dx.doi.org/10.1021/cb500640t

10. FIDALGO, TATIANA K. S. ; FREITAS-FERNANDES, LIANA B. ; ALMEIDA, FABIO C. L. ; VALENTE, ANA P. ; SOUZA, IVETE

P. R. . Longitudinal evaluation of salivary profile from children with dental caries before and after treatment. Metabolomics (Dordrecht.

Print), v. 11, p. 583-593, 2014. http://dx.doi.org/10.1007/s11306-014-0717-z

11. LÓPEZ-CASTILLA, ARACELYS ; DE MENEZES, RACHEL S. ; D’ ; DOS SANTOS, THAMIRES R. ; PIRES, JOSÉ R. . 1H, 15N and

13C resonance assignments and secondary structure prediction of Q4D059, a conserved and kinetoplastid-specific hypothetical protein

from Trypanosoma cruzi. Biomolecular NMR Assignments (Print), v. 9, p. 161-163, 2014. http://dx.doi.org/10.1007/s12104-014-9565-z

12. MANZINI, MARIANA C. ; PEREZ, KATIA R. ; RISKE, KARIN A. ; BOZELLI, JOSÉ C. ; SANTOS, TALITA L. ; DA SILVA,

MARCIA A. ; SARAIVA, GREICE K.V. ; POLITI, MARIO J. ; VALENTE, ANA P. ; ALMEIDA, FÁBIO C.L. ; CHAIMOVICH,

HERNAN ; RODRIGUES, MAGALI A. ; BEMQUERER, MARCELO P. ; SCHREIER, SHIRLEY ; CUCCOVIA, IOLANDA M. .

Peptide:lipid ratio and membrane surface charge determine the mechanism of action of the antimicrobial peptide BP100. Conformational

and functional studies. Biochimica et Biophysica Acta. Biomembranes, v. 1838, p. 1985-1999, 2014.

http://dx.doi.org/10.1016/j.bbamem.2014.04.004

13. MORAES, ADOLFO H. ; ACKERBAUER, DANIELA ; KOSTADINOVA, MARIA ; BUBLIN, MERIMA ; DE OLIVEIRA,

GUILHERME AUGUSTO ; FERREIRA, FÁTIMA ; ALMEIDA, FABIO C.L. ; BREITENEDER, HEIMO ; VALENTE, ANA PAULA .

Solution and high-pressure NMR studies of the structure, dynamics and stability of the cross-reactive allergenic cod parvalbumin Gad m

1. Proteins (Print), v. 82, p. n/a-n/a, 2014. http://dx.doi.org/10.1002/prot.24664

14. MUJO, AMANDA ; LIXA, CAROLINA ; CARNEIRO, LETÍCIA A. M. ; ANOBOM, CRISTIANE D. ; ALMEIDA, FÁBIO C. ;

PINHEIRO, ANDERSON S. . 1H, 15N and 13C resonance assignments of the RRM1 domain of the key post-transcriptional regulator

HuR. Biomolecular NMR Assignments (Print), v. 1, p. 1-2, 2014. http://dx.doi.org/10.1007/s12104-014-9592-9

15. QUEIROZ, I. N. L. ; WANG, X. ; GLUSHKA, J. N. ; SANTOS, G. R. C. ; VALENTE, A. P. ; PRESTEGARD, J. H. ; WOODS, R. J. ;

MOURAO, P. A. S. ; POMIN, V. H. . Impact of sulfation pattern on the conformation and dynamics of sulfated fucan oligosaccharides as

revealed by NMR and MD. Glycobiology (Oxford), v. 01, p. 01-02, 2014. http://dx.doi.org/10.1093/glycob/cwu184

16. RAMÍREZ, ROSA ; FALCÓN, ROSABEL ; IZQUIERDO, ALIENYS ; GARCÍA, ANGÉLICA ; ALVAREZ, MAYLING ; PÉREZ,

ANA BEATRIZ ; SOTO, YUDIRA ; MUNÉ, MAYRA ; DA SILVA, EMILIANA MANDARANO ; ORTEGA, ONEY ; MOHANA-

BORGES, RONALDO ; GUZMÁN, MARÍA G. . Recombinant dengue 2 virus NS3 protein conserves structural antigenic and

immunological properties relevant for dengue vaccine design. Virus Genes, v. 1, p. 00, 2014. http://dx.doi.org/10.1007/s11262-014-1087-

3

17. VENTURA, GUSTAVO TAVARES ; COSTA, EMMERSON CORRÊA BRASIL DA ; CAPACCIA, ANNE MIRANDA ; MOHANA-

BORGES, RONALDO . pH-Dependent Conformational Changes in the HCV NS3 Protein Modulate Its ATPase and Helicase Activities.



1. ALLONSO, D. ; VAZQUEZ, S. ; GUZMAN, M. G. ; MOHANA-BORGES, R. . High Mobility Group Box 1 Protein as an Auxiliary

Biomarker for Dengue Diagnosis. The American Journal of Tropical Medicine and Hygiene, v. 88, p. 506-509, 2013.

http://dx.doi.org/10.4269/ajtmh.2012.12-0619

2. ALMEIDA, F. C. L.; DO CARMO-GONÇALVES, PHELIPPE ; PINHEIRO, A. S. ; CORTINES, JULIANA ; FOLLMER, CRISTIAN .

α-Synuclein as an intrinsically disordered monomer: fact or artifact?. The FEBS Journal (Print), v. 280, p. n/a-n/a, 2013.

http://dx.doi.org/10.1111/febs.12471

3. BELGRANO, FABRICIO S. ; DE ABREU DA SILVA, ISABEL C. ; BASTOS DE OLIVEIRA, FRANCISCO M. ; FANTAPPIÉ,

MARCELO R. ; MOHANA-BORGES, RONALDO . Role of the Acidic Tail of High Mobility Group Protein B1 (HMGB1) in Protein

Stability and DNA Bending. Plos One, v. 8, p. e79572, 2013. http://dx.doi.org/10.1371/journal.pone.0079572

4. BRAGA, CAROLINA A. C. A. ; CORDEIRO, YRAIMA*. . Proteínas: Avaliação da estrutura secundária de proteínas por dicroísmo

circular. In: Monica Montero-Lomeli; Franklin David Rumjanek. (Org.). Técnicas em Biociências - Protocolos Comentados para o

Laboratório. 1ed.Rio de Janeiro: MedBook, 2013, v. 1, p. 59-62. *IN COLLABORATION WITH CORDEIRO [AL1] [BOOK

CHAPTER]

http://dx.doi.org/10.1002/jps.24641

http://dx.doi.org/10.1007/s00044-014-1058-1


http://dx.doi.org/10.1016/j.bmcl.2014.04.072

http://dx.doi.org/10.3109/13506129.2014.912208

http://dx.doi.org/10.1111/cea.12361


http://dx.doi.org/10.1021/bi401542v


http://dx.doi.org/10.1021/cb500640t

http://dx.doi.org/10.1007/s11306-014-0717-z

http://dx.doi.org/10.1007/s12104-014-9565-z


http://dx.doi.org/10.1002/prot.24664

http://dx.doi.org/10.1007/s12104-014-9592-9

http://dx.doi.org/10.1093/glycob/cwu184

http://dx.doi.org/10.1007/s11262-014-1087-3

http://dx.doi.org/10.1007/s11262-014-1087-3


http://dx.doi.org/10.4269/ajtmh.2012.12-0619

http://dx.doi.org/10.1111/febs.12471



53

5. DA COSTA, EMMERSON C. B. ; AMORIM, RAQUEL ; DA SILVA, FERNANDO C. ; ROCHA, DAVID R. ; PAPA, MICHELLE P. ;

DE ARRUDA, LUCIANA B. ; MOHANA-BORGES, RONALDO ; FERREIRA, VITOR F. ; TANURI, AMILCAR ; DA COSTA,

LUCIANA J. ; FERREIRA, SABRINA B. . Synthetic 1,4-Pyran Naphthoquinones Are Potent Inhibitors of Dengue Virus Replication.


6. DE OLIVEIRA, G. A. P. ; PEREIRA, E. G. ; FERRETTI, G. D. S. ; VALENTE, A. P. ; CORDEIRO, Y.* ; SILVA, J. L*. .

Intramolecular dynamics within the N-Cap-SH3-SH2 regulatory unit of the c-Abl tyrosine kinase reveal targeting to the cellular

membrane. The Journal of Biological Chemistry (Print), v. 288, p. 28331-28345, 2013. http://dx.doi.org/10.1074/jbc.m113.500926 IN

COLLABORATION WITH CORDEIRO AND SILVA (AL 1)

7. DE PAULA, V.S. ; GOMES, N.S.F. ; LIMA, L.G. ; MIYAMOTO, C.A. ; MONTEIRO, R.Q. ; ALMEIDA, F.C.L. ; VALENTE, A.P. .

Structural Basis for the Interaction of Human β-Defensin 6 and Its Putative Chemokine Receptor CCR2 and Breast Cancer Microvesicles.

Journal of Molecular Biology, v. 425, p. 4479-4495, 2013. http://dx.doi.org/10.1016/j.jmb.2013.08.001

8. DO AIDO-MACHADO, RODOLPHO ; SALMON, DIDIER ; PIRES, JOSÉ R. . 1H, 15N and 13C assignments of a putative peptidyl

prolyl cis-trans isomerase FKBP12 from Trypanosoma brucei. Biomolecular NMR Assignments (Print), v. 8, p. 133-135, 2013.

http://dx.doi.org/10.1007/s12104-013-9468-4

9. FAUSTINO, ANDRÉ F. ; CARVALHO, FILOMENA A. ; MARTINS, IVO C. ; CASTANHO, MIGUEL A.R.B. ; MOHANA-BORGES,

RONALDO ; ALMEIDA, FÁBIO C.L. ; DA POIAN, ANDREA T. ; SANTOS, NUNO C. . Dengue Virus Capsid Protein Interacts

Specifically with Very Low Density Lipoproteins. Nanomedicine, v. 10, p. 244-255, 2013. http://dx.doi.org/10.1016/j.nano.2013.06.004

10. FÁVERO-RETTO, MAELY P. ; PALMIERI, LEONARDO C. ; SOUZA, TATIANA A.C.B. ; ALMEIDA, FÁBIO C.L. ; LIMA, LUÍS

MAURICIO T.R. . Structural meta-analysis of regular human insulin in pharmaceutical formulations. European Journal of Pharmaceutics

and Biopharmaceutics, v. 85, p. 1112-1121, 2013. http://dx.doi.org/10.1016/j.ejpb.2013.05.005

11. FIDALGO, TATIANA K. S. ; FREITAS-FERNANDES, LIANA B. ; ANGELI, RENATA ; MUNIZ, ADRIANE M. S. ; GONSALVES,

ELICARDO ; SANTOS, RAQUEL ; NADAL, JURANDIR ; ALMEIDA, FABIO C. L. ; VALENTE, ANA P. ; SOUZA, IVETE P. R. .

Salivary metabolite signatures of children with and without dental caries lesions. Metabolomics (Dordrecht. Print), v. 9, p. 657-666, 2013.

http://dx.doi.org/10.1007/s11306-012-0484-7

12. FREIRE, JOÃO MIGUEL ; VEIGA, ANA SALOMÉ ; CONCEIÇÃO, THAÍS M. ; KOWALCZYK, WIOLETA ; MOHANA-BORGES,

R. ; ANDREU, DAVID ; SANTOS, NUNO C. ; DA POIAN, A. T. ; DA POIAN, ANDREA T. ; CASTANHO, MIGUEL A. R. B. .

Intracellular Nucleic Acid Delivery by the Supercharged Dengue Virus Capsid Protein. Plos One, v. 8, p. e81450, 2013.


13. GOMES-NETO, FRANCISCO ; VALENTE, ANA ; ALMEIDA, FABIO . Modeling the Interaction of Dodecylphosphocholine Micelles

with the Anticoccidial Peptide PW2 Guided by NMR Data. Molecules (Basel. Online), v. 18, p. 10056-10080, 2013.

http://dx.doi.org/10.3390/molecules180810056

14. LATGÉ, CRISTIANE ; CABRAL, KÁTIA M. S. ; ALMEIDA, MARCIUS S. ; FOGUEL, DÉBORA* . 1H-, 13C- and 15N-NMR

assignment of the N-terminal domain of human cerebral dopamine neurotrophic factor (CDNF). Biomolecular NMR Assignments (Print),

v. 7, p. 101-103, 2013. http://dx.doi.org/10.1007/s12104-012-9388-8 IN COLLABORATION WITH FOGUEL(AL 2)

15. LÓPEZ-CASTILLA, ARACELYS ; PAZOS, FABIOLA ; SCHREIER, SHIRLEY ; RICARDO PIRES, JOSÉ . Solution NMR analysis of

the interaction between the actinoporin Sticholysin I and DHPC micelles-Correlation with backbone dynamics. Proteins (Print), v. 82, p.

n/a-n/a, 2013. http://dx.doi.org/10.1002/prot.24475

16. MACHADO, LUCIANA E. F. ; PUSTOVALOVA, YULIA ; KILE, ANDREW C. ; POZHIDAEVA, ALEXANDRA ; CIMPRICH,

KARLENE A. ; ALMEIDA, FABIO C. L. ; BEZSONOVA, IRINA ; KORZHNEV, DMITRY M. . PHD domain from human SHPRH.

Journal of Biomolecular NMR, v. 56, p. 393-399, 2013. http://dx.doi.org/10.1007/s10858-013-9758-2

17. MORAES, A.H. ; ACKERBAUER, D. ; KOSTADINOVA, M. ; BUBLIN, M. ; FERREIRA, F. ; ALMEIDA, F. C. L. ; BREITENEDER,

H. ; VALENTE, ANA PAULA . 1H, 13C and 15N resonance assignments and second structure information of Gad m 1: a β-parvalbumin

allergen from Atlantic cod (Gadus morhua). Biomolecular NMR Assignments (Print), v. 7, p. 133-136, 2013.

http://dx.doi.org/10.1007/s12104-012-9393-y

18. PAULA, V. S. DE ; GOMES NSF ; LIMA LG ; MIYAMOTO, CA ; MONTEIRO RQ ; FCL, A. ; VALENTE, ANA PAULA, ANA P.

VALENTE . Structural Basis for the Interaction of Human -Defensin 6 and Its Putative Chemokine Receptor CCR2 and Breast Cancer

Microvesicles. Journal of Molecular Biology, v. 425, p. 4479-4495, 2013. http://dx.doi.org/10.1016/j.jmb.2013.08.001

19. SILVA, EMILIANA M. ; CONDE, JONAS N. ; ALLONSO, DIEGO ; NOGUEIRA, MAURICIO L. ; MOHANA-BORGES, RONALDO

. Mapping the Interactions of Dengue Virus NS1 Protein with Human Liver Proteins Using a Yeast Two-Hybrid System: Identification of

C1q as an Interacting Partner. Plos One, v. 8, p. e57514, 2013. http://dx.doi.org/10.1371/journal.pone.0057514

20. VALENTE, ANA ; DE PAULA, VIVIANE ; ALMEIDA, FABIO . Revealing the Properties of Plant Defensins through Dynamics.

Molecules (Basel. Online), v. 18, p. 11311-11326, 2013. http://dx.doi.org/10.3390/molecules180911311



http://dx.doi.org/10.1016/j.jmb.2013.08.001

http://dx.doi.org/10.1007/s12104-013-9468-4

http://dx.doi.org/10.1016/j.nano.2013.06.004

http://dx.doi.org/10.1016/j.ejpb.2013.05.005

http://dx.doi.org/10.1007/s11306-012-0484-7



http://dx.doi.org/10.1007/s12104-012-9388-8

http://dx.doi.org/10.1002/prot.24475

http://dx.doi.org/10.1007/s10858-013-9758-2

http://dx.doi.org/10.1007/s12104-012-9393-y





54

AL 4 - Associated Laboratory of Pharmacologic

Proteomic

- Coordinator:

Russolina Zingali - Instituto de Bioquímica Médica (IBqM/UFRJ)

- Researchers from national institutions: Bianca Cruz Neves – IQ/UFRJ

Márcia Regina Soares da Silva – IQ/UFRJ

Robson Queiroz Monteiro – IBqM/UFRJ


André Luiz Pinto Guedes Lourenço (UFRJ)

Andreia da Silva de Oliveira (UFRJ)

Carlos Correa Netto (UFRJ)

Denise de Abreu Pereira (UFRJ)

Kristie Aimi Yamamoto (UFRJ)

Marjolly Caruso Brígido (UFRJ)

Ricardo Teixeira (UFRJ)

Vanessa Siqueira Sandim (UFRJ)


Araci Maria da Rocha Rondon (UFRJ)

Barbara Barbosa Succar (UFRJ)

Fausto Gueths Gomes (UFRJ)

Karina Martins Cardoso (UFRJ)

Michele Rocha Castro (UFRJ)

Raiana Apolinário de Paula (UFPE)

Rosane de Oliveira Nunes (UFRJ)

Tainá Gomes (UFRJ)

Tatiana Pereira Pena Dutra (UFRJ)

Victor da Conceição David (UFRJ)

Vitor Hugo Luna R. de Almeida (UFRJ)

Wilber de Sousa Alves (UFRJ)


Carolina Baeta Salvador Várady (UFRJ)

Giulia Naranjo Aranha (UFRJ)

Igor Patrick Vasconcelos Vieira (UFRJ)

Jessica Matos Kleiz Ferreira (UFRJ)

Larissa Gonçalves Machado (UFRJ)

Rafael Sarmet Moreira Uchôa (UFRJ)

Rafaela de Assiz Louback (UFRJ)

Vinícius Simas Grilo (UFRJ)


Giselli Cristini Domiciano Abrahao (UERJ)

Taissa Guerrero (UFRJ)

The Proteomic Unity focuses on two main

research projects:

1. Proteomics, Genomics and

Bioinformatics in the study of the

interaction between pathogenic and non-

pathogenic microorganisms with their

hosts.

2. Prospective proteomics.

The group has been collaborating with

many laboratories from INBEB in projects

that envisage the proteomic characterization

of biological processes such as performing

proteomics of cell-cell interactions in health

and disease, along with Associated

Laboratory 17, headed by Dr. Vieyra

(Lindoso et al, 2016). In other hand, we

achieved some new insights on the Golgi

complex of Tritrichomonas foetus along

with Dr. Benchimol and AL 12 (de

Andrade et al, 2014). And, within the

Associated Laboratory 11, led by Dr.

Souto-Padrón, we showed that Crovirin, a

snake venom cysteine-rich secretory protein

(CRISP) has a promising activity against

Trypanosomes and Leishmania (Adade et.

al., 2014).

Besides that, we summarized below some

of the other main results obtained during

the four years’ period covered by this report

(2013 to 2016):

Proteomic analysis of human samples

Through proteomic analysis, we revealed

differentially secreted proteins in the urine

from patients with clear cell renal cell

carcinoma. The proteins kininogen-1,


55

apolipoprotein D, fibrinogen, and

haptoglobin presented similar quantitative

protein profiles according to MSE and 2DE

approaches. Urine composition can reflect

kidney physiology and can be used to detect

markers for renal diseases. Moreover,

characterization of the secretome is likely

to assist in the investigation of new drugs

for biological targets and diagnose the

ccRCC at an early stage (Sandim et al.,

2016).

Within similar approach, we did compare

saliva from individuals with and without

oral leukoplakia (Figure 1). CK10 appears

to be an interesting protein and should be

further studied in oral carcinogenesis and as

possible biomarker (Camisasca et al.,

2016).

Figure 1: Patterns of keratin 10 positivity found in OL tissues. Focal (A) and diffuse positivity were observed

(B – F). This last pattern was most commonly found and could be observed as positivity in columns (B) or

continuous (C). Basal and parabasal keratinocytes were spared (D – inset from the dotted area in C) except in

one case, in which CK10 stained all layers (F – inset form dotted area in E). Immunohistochemistry for CK10

(A, C – objective 10x; B, E – objective 4x; D, F – objective 20x).

We also performed proteomics analysis of

tissue samples from patients with squamous

cell carcinoma of the penis (SCCP) and

positive to human papillomavirus (HPV).

We identified many proteins also directly

involved in the development of other types

of cancers and therefore, suitable for

analysis. Remarkably, this work reinforces

that the C3 complement protein is a strong

biomarker candidate for evaluating SCCP

patients (Koifman, 2015).

Snake venoms and antivenoms

The antiserum therapy is the most effective

treatment available to save envenomations

by venomous animals. The productions of

this immunobiologicals have been done for

the same principle from their discovery,

immunizing animals with whole venom.

Our group has studied the

immunochemistry of snake venoms and

antivenoms to identify molecules that

escape of antibodies recognition and

neutralization. Research in this field can

bring improvements and effectiveness in

these products and treatment of snakebite.

In this line, we investigated the venomics

and antivenomics of Bothrops erythromelas

from five geographic populations within the

Caatinga ecoregion of northeastern Brazil.

Those venoms exhibit highly conserved

venom proteomes. They also showed

qualitatively and quantitatively overlapping

antivenomic profiles against antivenoms

generated in Vital Brazil (BR) and

Clodomiro Picado (CR) Institutes, using

different venoms in the immunization

mixtures. The paraspecificity exhibited by

the Brazilian SAB and the Costa Rican

BCL antivenoms against venom toxins

from B. erythromelas indicates large

immunoreactive epitope conservation

across genus Bothrops during the last ~14

million years, thus offering promise for the

possibility of generating a broad-spectrum

bothropic antivenom (Jorge et. al., 2015).

We also performed the comparisons of the

venom proteomes and 38 transcriptomes of

Differences between renal effects of venom

from two Bothrops jararaca populations

from southeastern and southern Brazil.

They revealed notable interpopulational

variability. Mirroring their compositional

divergence, the two geographic B. jararaca

venom pools showed distinct bioactivity

profiles. The remarkable paraspecificity

exhibited by the Brazilian and the Costa

Rican antivenoms indicates large


56

immunoreactive epitope conservation

across the natural history of Bothrops, a

genus that has its roots in the middle

Miocene (Gonçalves-Machado et. al.,

2016).

Snake venom metalloproteinases (SVMPs)

are major components in most viperid

venoms that induce disturbances in the

hemostatic system and tissues of animals

envenomated by snakes. We evaluated the

interference of five isolated SVMPs in

blood coagulation of humans, birds and

small rodents. In conclusion, functionally

distinct forms of SVMPs were found in B.

neuwiedi venom that affect distinct

mechanisms in the coagulation system of

humans, birds and small rodents. The

functional diversity of SVMPs shown in

this study clarify the importance of this

class of toxins for the feeding ecology

of Bothrops snakes and suggest further

directions for studies on the design of more

efficient antivenoms (Bernardoni et al.,

2014).

Also, Snake venoms constitute a major

source of molecules capable of modulating

hemostasis. Some of these molecules have

been already characterized as potent

antithrombotic agents in vivo in animal

models.

Antithrombotics

Still within the study of snake venoms, we

also look for new antithrombotic

substances. Bothrojaracin is a 27 kDa C-

type lectin-like protein from Bothrops

jararaca snake venom. In our study,

bothrojaracin showed significant

antithrombotic activity in a rat venous

thrombosis model elicited by

thromboplastin combined with stasis. Also,

it effectively protected mice from thrombin-

induced fatal thromboembolism. We

conclude that bothrojaracin is a potent

antithrombotic agent in vivo and may serve

as a prototype for the development of new

zymogen-directed drugs that could result in

prolonged half-life and possible decreased

hemorrhagic risk (Assafim et. al., 2016).

Bacteria can also be sources of

antithrombotics. Ecotin is an Escherichia

coli-derived protein that can inhibit serine

proteases. We analyzed the effect of ecotin-

WT and two mutated (Met84Arg and

Met85Arg, ecotin-RR) to determine their

ability to prevent thrombus formation using

in vivo and in vitro models. In conclusion,

our results suggests that ecotin-WT

prevents thrombus formation through the

inhibition of Factor Xa or upstream, while

ecotin-RR, by its potent inhibition of

thrombin, is more efficient when the

thrombus is associated with thrombin burst.

Thus, both ecotins displayed potent in vivo

antithrombotic effects that were not

associated with bleeding (Figure 2). These

results demonstrated the potential of those

molecules as templates for the design of

new anticoagulation molecules

(Wermelinger et al., 2015).

Figure 2: The effects of ecotins on an in vivo

model of pulmonary thromboembolism induced

by thrombin. (A) Ecotin WT and RR at a dose of 1

mg/kg administered 30 min before the induction

of thromboembolism represent a percentage of

survival of the population and (B) ecotin RR at a

dose of 1 and 0.5 mg/kg administered 30 min

before the induction of thromboembolism

represent a percentage of survival of the

population. The control group received PBS

instead of ecotin. The results shown represent the

mean ± SD of three groups of five animals each.

***p < 0.001 or **p < 0.01 compared to values

observed in the absence of ecotin. Mallory’s

phosphotungstic acid hematoxylinstaining of

mouse lung before the thrombin-induced acute

pulmonary embolism model. Fibrin formed in the

blood vessel stained an intense blue, (C and D)

pulmonary thromboembolisms were evaluated in

control animals, which only received PBS, (E and

F) in the group treated with ecotin-WT at a dose

of 1 mg/kg and (G and H) in the ecotin-RR treated

animals with a dose of 1 mg/kg, (I and J) and in

the ecotin-RR treated animals with dose of 0.5

mg/kg. Minor and major magnification on the left

and right, respectively. Asterisk represents the

completely or partially clear vessels. Arrows show

completely obstructed vessels.


57

Dengue virus infection

In the previous report, we show our first

results on the analysis of the secreted

proteins of HepG2 cells infected or not with

the Dengue virus (Higa, et al., 2008). We

now continued the analyses on the

peptidomic (<10kDa) and a different group

of strategies with more sensitive

equipments permited the identification of

more than 50 peptides. We predicted

consistent differences between the

proteolytic processing occurring in mock

and DENV-infected samples, raising, for

the first time, the hypothesis that

differential proteolysis of secreted

molecules would be involved in the

pathogenesis of dengue (Caruso, et. al.,

2016). We also demonstrated that DENV

infection modulates α-enolase secretion in

HepG2 cells in a dose-dependent manner,

but has no effect on its gene expression and

on the intracellular content of the protein

(Higa, et. al., 2014).

In another study, we found that Moringa

oleifera seed cake (which is the coproduct

of oil extraction) may be a good source of

insecticidal lectin with high potential to be

used in control of A. aegypti. While it

stimulates the oviposition by females, it

could kill the eggs or larvae that may arise

from them. Furthermore, the larvae did not

express different enzymes in response to

lectin effect (Oliveira et al., 2016).

AL 4 main publications in 2016: 1. ABEYDEERA, N. DINUKA ; EGLI, MARTIN ; COX, NEHEMIAH ; MERCIER, KAREN ; CONDE, JONAS NASCIMENTO ;

PALLAN, PRADEEP S. ; MIZURINI, DANIELLA M. ; SIERANT, MALGORZATA ; HIBTI, FATIMA-EZZAHRA ; HASSELL, TOM

; WANG, TIANZHI ; LIU, FENG-WU ; LIU, HONG-MIN ; MARTINEZ, CARLOS ; SOOD, ANIL K. ; LYBRAND, TERRY P. ;

FRYDMAN, CHIRAZ ; MONTEIRO, ROBSON Q. ; GOMER, RICHARD H. ; NAWROT, BARBARA ; YANG, XIANBIN . Evoking

picomolar binding in RNA by a single phosphorodithioate linkage. Nucleic Acids Research, v. 44, p. 8052-8064, 2016.

http://dx.doi.org/10.1093/nar/gkw725

2. ASSAFIM, MARIANE ; FRATTANI, FLÁVIA S. ; FERREIRA, MARCOS S. ; SILVA, DIONE M. ; MONTEIRO, R. Q. ; ZINGALI, R.

B. . Exploiting the antithrombotic effect of the (pro)thrombin inhibitor bothrojaracin. Toxicon (Oxford), v. 16, p. 30136-30142, 2016.

http://dx.doi.org/10.1016/j.toxicon.2016.05.007

3. ASSUMPÇÃO, TERESA C. ; MA, DONGYING ; MIZURINI, DANIELLA M. ; KINI, R. MANJUNATHA ; RIBEIRO, JOSÉ M. C. ;

KOTSYFAKIS, MICHAIL ; MONTEIRO, ROBSON Q. ; FRANCISCHETTI, IVO M. B. . In Vitro Mode of Action and Anti-thrombotic

Activity of Boophilin, a Multifunctional Kunitz Protease Inhibitor from the Midgut of a Tick Vector of Babesiosis, Rhipicephalus

microplus. PLoS Neglected Tropical Diseases (Online), v. 10, p. e0004298, 2016. http://dx.doi.org/10.1371/journal.pntd.0004298

4. BOENTE, RENATA F. ; PAUER, HEIDI ; SILVA, DEBORAH N.S. ; FILHO, JOAQUIM SANTOS ; SANDIM, VANESSA ;

ANTUNES, LUIS CAETANO M. ; FERREIRA, ROSANA BARRETO ROCHA ; ZINGALI, RUSSOLINA B. ; DOMINGUES,

REGINA M.C.P. ; LOBO, LEANDRO A. . Differential proteomic analysis of outer membrane enriched extracts of Bacteroides fragilis

grown under bile salts stress. Anaerobe (London. Print), v. 39, p. 84-90, 2016. http://dx.doi.org/10.1016/j.anaerobe.2016.03.003

5. CAMISASCA, DANIELLE RESENDE ; DA RÓS GONÇALVES, LORENA ; SOARES, MÁRCIA REGINA ; SANDIM, VANESSA ;

NOGUEIRA, F. C. S. ; GARCIA, CARLOS HENRIQUE SARAIVA ; SANTANA, RODRIGO ; DE OLIVEIRA, SILVIA PAULA ;

BUEXM, LUISA AGUIRRE ; DE FARIA, PAULO ANTÔNIO SILVESTRE ; DIAS, FERNANDO LUIZ ; DE ABREU PEREIRA,

DENISE ; ZINGALI, R. B. ; ALVES, GILDA ; LOURENÇO, SIMONE QUEIROZ CHAVES . A proteomic approach to compare saliva

from individuals with and without oral leukoplakia. Journal of Proteomics (Print), v. xx, p. 1, 2016.


6. CARUSO, MARJOLLY B. ; TRUGILHO, MONIQUE R.O. ; HIGA, L. M. ; TEIXEIRA-FERREIRA, ANDRÉ S. ; PERALES, JONAS ;

DA POIAN, ANDREA T. ; ZINGALI, R. B. . Proteomic analysis of the secretome of HepG2 cells indicates differential proteolytic

processing after infection with dengue virus. Journal of Proteomics (Print), v. 1, p. 1-6, 2016. 10.1016/j.jprot.2016.07.011

7. DE ALMEIDA, VITOR HUGO ; MONTEIRO, ROBSON Q. . Protease-activated receptor 1 (PAR1): a promising target for the treatment

of glioblastoma?. Translational Cancer Research, v. 5, p. S1274-S1280, 2016. http://dx.doi.org/10.21037/tcr.2016.11.30

8. DE OLIVEIRA, ANA PATRÍCIA SILVA ; DE SANTANA SILVA, LIVIA LAIS ; DE ALBUQUERQUE LIMA, THÂMARAH ;

PONTUAL, EMMANUEL VIANA ; DE LIMA SANTOS, NATALY DINIZ ; BREITENBACH BARROSO COELHO, LUANA

CASSANDRA ; DO AMARAL FERRAZ NAVARRO, DANIELA MARIA ; ZINGALI, R. B. ; NAPOLEÃO, T. H. ; PAIVA,

PATRÍCIA MARIA GUEDES . Biotechnological value of Moringa oleifera seed cake as source of insecticidal lectin against Aedes

aegypti. PROCESS BIOCHEMISTRY, v. 51, p. 1683-1690, 2016. http://dx.doi.org/10.1016/j.procbio.2016.06.026

9. DOBLER, LETICIA ; VILELA, LEONARDO F. ; ALMEIDA, RODRIGO V. ; NEVES, BIANCA C. . Rhamnolipids in perspective: gene

regulatory pathways, metabolic engineering, production and technological forecasting. New Biotechnology (Print), v. 33, p. 123-135,

2016. http://dx.doi.org/10.1016/j.nbt.2015.09.005

10. FERREIRA, FELIPE ROBERTO BORBA ; DA SILVA, POLLYANNA MICHELLE ; SOARES, TATIANA ; GONÇALVES

MACHADO, LARISSA ; DE ARAÚJO, LARISSA CARDOSO CORRÊA ; DA SILVA, TERESINHA GONÇALVES ; DE MELLO,

GABRIELA SOUTO VIEIRA ; GALDINO DA ROCHA PITTA, MAIRA ; DE MELO REGO, MOACYR JESUS BARRETO ;

PONTUAL, EMMANUEL VIANA ; ZINGALI, RUSSOLINA BENEDETA ; NAPOLEÃO, THIAGO HENRIQUE ; PAIVA,

PATRÍCIA MARIA GUEDES . Evaluation of antimicrobial, cytotoxic, and hemolytic activities from venom of the spider Lasiodora sp..

Toxicon (Oxford), v. 122, p. 119-126, 2016. http://dx.doi.org/10.1016/j.toxicon.2016.09.019

11. FERREIRA, RAFAEL M. ; MOREIRA, LEANDRO M. ; FERRO, JESUS A. ; SOARES, MARCIA R.R. ; LAIA, MARCELO L. ;

VARANI, ALESSANDRO M. ; DE OLIVEIRA, JULIO C.F. ; FERRO, MARIA INES T. . Unravelling potential virulence factor

candidates in Xanthomonas citri . subsp. citri by secretome analysis. PEERJ, v. 4, p. e1734, 2016. http://dx.doi.org/10.7717/peerj.1734

12. GARCIA, GIZELE D. ; DE O. SANTOS, EIDY ; SOUSA, GABRIELE V. ; ZINGALI, RUSSOLINA ; THOMPSON, CRISTIANE C. ;

THOMPSON, FABIANO L. . Metaproteomics reveals metabolic transitions between healthy and diseased stony coral. Molecular Ecology

(Print), v. 25, p. 4632-4644, 2016. http://dx.doi.org/10.1111/mec.13775

13. GONÇALVES-MACHADO, LARISSA ; PLA, DAVINIA ; SANZ, LIBIA ; JORGE, ROBERTA JEANE B. ; LEITÃO-DE-ARAÚJO,

MOEMA ; ALVES, MARIA LÚCIA M. ; ALVARES, DIEGO JANISCH ; DE MIRANDA, JOARI ; NOWATZKI, JENIFER ; DE

MORAIS-ZANI, KAREN ; FERNANDES, WILSON ; TANAKA-AZEVEDO, ANITA MITICO ; FERNÁNDEZ, JULIÁN ; ZINGALI,

RUSSOLINA B. ; GUTIÉRREZ, JOSÉ MARÍA ; CORRÊA-NETTO, CARLOS ; CALVETE, JUAN J. . Combined venomics, venom

gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the

Brazilian Atlantic rainforest. Journal of Proteomics (Print), v. 135, p. 73-89, 2016. http://dx.doi.org/10.1016/j.jprot.2015.04.029

14. JORGE, ROBERTA JEANE BEZERRA ; JORGE, ANTÔNIO RAFAEL COELHO ; DE MENEZES, RAMON RÓSEO PAULA

PESSOA BEZERRA ; MELLO, CLARISSA PERDIGÃO ; LIMA, DANYA BANDEIRA ; SILVEIRA, JOÃO ALISON DE MORAES ;

ALVES, NATACHA TERESA QUEIROZ ; MARINHO, ALINE DIOGO ; XIMENES, RAFAEL MATOS ; NETTO, CARLOS

CORRÊA ; GONÇALVES MACHADO, LARISSA ; ZINGALI, RUSSOLINA BENEDETA ; MARTINS, ALICE MARIA COSTA ;

http://dx.doi.org/10.1093/nar/gkw725


http://dx.doi.org/10.1371/journal.pntd.0004298

http://dx.doi.org/10.1016/j.anaerobe.2016.03.003


https://doi.org/10.1016/j.jprot.2016.07.011

http://dx.doi.org/10.21037/tcr.2016.11.30


http://dx.doi.org/10.1016/j.nbt.2015.09.005


http://dx.doi.org/10.7717/peerj.1734

http://dx.doi.org/10.1111/mec.13775



58

MONTEIRO, HELENA SERRA AZUL . Differences between renal effects of venom from two Bothrops jararaca populations from

southeastern and southern Brazil. Toxicon (Oxford), v. 125, p. 84-90, 2016. http://dx.doi.org/10.1016/j.toxicon.2016.11.249

15. LINDOSO, RAFAEL S. ; SANDIM, VANESSA ; COLLINO, FEDERICA ; CARVALHO, ADRIANA B. ; DIAS, JULIANA ; DA

COSTA, MILENE R. ; ZINGALI, RUSSOLINA B. ; VIEYRA, ADALBERTO* . Proteomics of cell-cell interactions in health and

disease. Proteomics (Weinheim. Print), v. 16, p. 328-344, 2016. http://dx.doi.org/10.1002/pmic.201500341 *IN COLLABORATION

WITH VIEYRA (AL 17)

16. LIXA, CAROLINA ; MARQUES, ADRIANA F. ; CORTINES, JULIANA R. ; NEVES, BIANCA C. ; OLIVEIRA, DANIELLE M.P. ;

ANOBOM, CRISTIANE D. ; LIMA, LUÍS MAURÍCIO T.R. ; PINHEIRO, ANDERSON S. . Refolding, purification, and preliminary

structural characterization of the DNA-binding domain of the quorum sensing receptor RhlR from Pseudomonas aeruginosa. Protein

Expression and Purification (Print), v. 121, p. 31-40, 2016. http://dx.doi.org/10.1016/j.pep.2016.01.006

17. MONTEIRO, ROBSON; LIMA, LUIZE ; GONÇALVES, NATHÁLIA ; DE SOUZA, MAYARA ; LEAL, ANA ; DEMASI, MARCOS ;

SOGAYAR, MARI ; CARNEIRO'LOBO, TATIANA . Hypoxia regulates the expression of tissue factor pathway signaling elements in a

rat glioma model. Oncology Letters, v. 12, p. 315-322, 2016. http://dx.doi.org/10.3892/ol.2016.4593

18. NUNES, ALESSANDRA T. ; BRITOOLIVEIRA, NATHALIA F.DANIELE S. ; ARAUJO, GABRIEL D. T. ; NOGUEIRA, FABIO

CESAR S. ; DOMONT, GILBERTO B. ; MOREIRA, MONICA F. ; MOREIRA, LEANDRO M. ; SOARES, MARCIA R. ; MELO,

ANA C. A. . Comparative proteome analysis reveals that blood and sugar meals induce differential protein expression in Aedes aegypti

female heads. Proteomics (Weinheim. Print), v. 16, p. 2582-2586, 2016. http://dx.doi.org/10.1002/pmic.201600126

19. PROVENZANO, JOSÉ CLAUDIO ; ANTUNES, HENRIQUE S. ; ALVES, FLÁVIO R.F. ; RÔÇAS, ISABELA N. ; ALVES, WILBER

S. ; SILVA, MÁRCIA R.S. ; SIQUEIRA, JOSÉ F. . Host-Bacterial Interactions in Post-treatment Apical Periodontitis: A Metaproteome

Analysis. Journal of Endodontics, v. 42, p. 880-885, 2016. http://dx.doi.org/10.1016/j.joen.2016.02.013

20. SANDIM, VANESSA ; PEREIRA, DENISE DE ABREU ; KALUME, DÁRIO ELUAN ; OLIVEIRA-CARVALHO, ANA LUCIA ;

ORNELLAS, ANTONIO AUGUSTO ; SOARES, MARCIA REGINA ; ALVES, GILDA ; ZINGALI, RUSSOLINA BENEDETA .

Proteomic analysis reveals differentially secreted proteins in the urine from patients with clear cell renal cell carcinoma. Urologic

Oncology, v. 34, p. 5.e11-5.e25, 2016. https://doi.org/10.1016/j.urolonc.2015.07.016

AL 4 main publications in 2015: 1. AZEREDO, ELZINANDES LEAL DE ; MONTEIRO, ROBSON Q. ; DE-OLIVEIRA PINTO, LUZIA MARIA . Thrombocytopenia in

Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators.

Mediators of Inflammation (Print), v. 2015, p. 1-16, 2015. http://dx.doi.org/10.1155/2015/313842

2. BARBOZA, THIAGO ; GOMES, TAINÁ ; MIZURINI, DANIELLA M. ; MONTEIRO, ROBSON Q. ; KÖNIG, SANDRA ;

FRANCISCHETTI, IVO M.B. ; SIGNORETTI, PAULA V.P. ; RAMOS, ISALIRA P. ; GUTFILEN, BIANCA ; SOUZA, SERGIO A.L. .

99mTc-ixolaris targets glioblastoma-associated tissue factor: In vitro and pre-clinical applications. Thrombosis Research, v. 15, p. 30011-

30016, 2015. http://dx.doi.org/10.1016/j.thromres.2015.05.032

3. JABLONKA, WILLY ; KOTSYFAKIS, MICHALIS ; MIZURINI, DANIELLA M. ; MONTEIRO, ROBSON Q. ; LUKSZO, JAN ;

DRAKE, STEVEN K. ; RIBEIRO, JOSÉ M. C. ; ANDERSEN, JOHN F. . Identification and Mechanistic Analysis of a Novel Tick-

Derived Inhibitor of Thrombin. Plos One, v. 10, p. e0133991, 2015. http://dx.doi.org/10.1371/journal.pone.0133991

4. JORGE, ROBERTA JEANE B. ; MONTEIRO, HELENA S.A. ; GONÇALVES-MACHADO, LARISSA ; GUARNIERI, MÍRIAM C. ;

XIMENES, RAFAEL M. ; BORGES-NOJOSA, DIVA M. ; LUNA, KARLA P. DE O. ; ZINGALI, RUSSOLINA B. ; CORRÊA-

NETTO, CARLOS ; GUTIÉRREZ, JOSÉ MARÍA ; SANZ, LIBIA ; CALVETE, JUAN J. ; PLA, DAVINIA . Venomics and

antivenomics of Bothrops erythromelas from five geographic populations within the Caatinga ecoregion of northeastern Brazil. Journal of

Proteomics (Print), v. 114, p. 93-114, 2015. http://dx.doi.org/10.1016/j.jprot.2014.11.011

5. KOIFMAN, L. ; ORNELLAS, P. ; ORNELLAS, A. A ; PEREIRA, D. A. ; ZINGALI, R. B. ; CAVALCANTI, S. M. B. ; AFONSO, L. A.

; SANDIM, V ; ALVES, G. . Proteomics analysis of tissue samples from patients with squamous cell carcinoma of the penis and positive

to human papillomavirus. International Braz J Urol (Online), v. 41, p. 642-654, 2015. http://dx.doi.org/10.1590/S1677-

5538.IBJU.2014.0051

6. MIZURINI, DANIELLA M. ; ASLAN, JORGEANE S. ; GOMES, TAINÁ ; MA, DONGYING ; FRANCISCHETTI, IVO M. B. ;

MONTEIRO, ROBSON Q. . Salivary Thromboxane A2-Binding Proteins from Triatomine Vectors of Chagas Disease Inhibit Platelet-

Mediated Neutrophil Extracellular Traps (NETs) Formation and Arterial Thrombosis. PLoS Neglected Tropical Diseases (Online), v. 9, p.

e0003869, 2015. http://dx.doi.org/10.1371/journal.pntd.0003869

7. MOREIRA, L. M. ; FACINCANI, A. P. ; FERREIRA, C. B. ; MARINI, R. ; FERRO, M. I. T. ; GOZZO, FABIO C. ; DE OLIVEIRA,

J.C.F. ; FERRO, J.A. ; SOARES, MÁRCIA R . Chemotactic signal transduction and phosphate metabolism as adaptive strategies during

citrus canker induction by Xanthomonas citri. Functional & Integrative Genomics (Print), v. x, p. x, 2015.

http://dx.doi.org/10.1007/s10142-014-0414-z

8. MOREIRA, L. M. ; SOARES, MARCIA R . CIÊNCIAS GENÔMICAS: FUNDAMENTOS E APLICAÇÕES. 1. ed. Ribeirão Preto, SP:

Editora Cubo, 2015. v. 1. 403p . [BOOK CHAPTER]

9. PEREIRA, ADRIANA S. A. ; CAVALCANTI, MARÍLIA G. S. ; ZINGALI, RUSSOLINA B. ; LIMA-FILHO, JOSÉ L. ; CHAVES,

MARIA E. C. . Isoforms of Hsp70-binding human LDL in adult Schistosoma mansoni worms. Parasitology Research (1987. Print), v.

114, p. 1145-1152, 2015. http://dx.doi.org/10.1007/s00436-014-4292-z

10. PROVENZANO, JOSÉ CLAUDIO ; RÔÇAS, ISABELA N. ; TAVARES, LUÍS FERNANDO D. ; NEVES, BIANCA CRUZ ;

SIQUEIRA, JOSÉ F. . Short-chain Fatty Acids in Infected Root Canals of Teeth with Apical Periodontitis before and after Treatment.

Journal of Endodontics, v. 41, p. 831-835, 2015. http://dx.doi.org/10.1016/j.joen.2015.02.006

11. VILELA, LEONARDO DE FIGUEIREDO ; DE ARAUJO, VERÔNICA PARENTE GOMES ; PAREDES, RAQUEL DE SOUSA ;

BON, ELBA PINTO DA SILVA ; TORRES, FERNANDO ARARIPE GONÇALVES ; NEVES, BIANCA CRUZ ; ELEUTHERIO, ELIS

CRISTINA ARAÚJO . Enhanced xylose fermentation and ethanol production by engineered Saccharomyces cerevisiae strain. AMB

Express, v. 5, p. 16, 2015. http://dx.doi.org/10.1186/s13568-015-0102-y

12. WERMELINGER, LUCIANA SERRÃO ; FRATTANI, FLÁVIA SERRA ; CARNEIRO-LOBO, TATIANA CORREA ; CRAIK,

CHARLES S. ; CASTRO, HELENA CARLA ; ZINGALI, R. B. . Ecotin: Exploring a feasible antithrombotic profile. International

Journal of Biological Macromolecules, v. 78, p. 296-303, 2015. http://dx.doi.org/10.1016/j.ijbiomac.2015.03.071

AL 4 main publications in 2014: 1. ADADE, CAMILA M. ; CARVALHO, ANA LÚCIA O. ; TOMAZ, MARCELO A. ; COSTA, TATIANA F. R. ; GODINHO, JOSEANE

L. ; MELO, PAULO A. ; LIMA, ANA PAULA C. A. ; RODRIGUES, JULIANY C. F. ; ZINGALI, RUSSOLINA B. ; SOUTO-

PADRÓN, THAÏS* . Crovirin, a Snake Venom Cysteine-Rich Secretory Protein (CRISP) with Promising Activity against Trypanosomes

and Leishmania. PLoS Neglected Tropical Diseases (Online), v. 8, p. e3252, 2014. http://dx.doi.org/10.1371/journal.pntd.0003252 *IN

COLLABORATION WITH SOUTO-PADRÓN (AL 11)

2. BERNARDONI, JULIANA L. ; SOUSA, LEIJIANE F. ; WERMELINGER, LUCIANA S. ; LOPES, ALINE S. ; PREZOTO,

BENEDITO C. ; SERRANO, SOLANGE M. T. ; ZINGALI, RUSSOLINA B. ; MOURA-DA-SILVA, ANA M. . Functional Variability

of Snake Venom Metalloproteinases: Adaptive Advantages in Targeting Different Prey and Implications for Human Envenomation. Plos


3. CARNEIRO-LOBO, T. C. ; LIMA, M. T. ; MARIANO-OLIVEIRA, A. ; DUTRA-OLIVEIRA, A. ; OBA-SHINJO, S. M. ; MARIE, S. K.

; SOGAYAR, M. C. ; MONTEIRO, R.Q. . Expression of tissue factor signaling pathway elements correlates with the production of

vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. Oncology Reports, v. 31, p. 679-686, 2014.

4. DE ANDRADE ROSA, IVONE ; CARUSO, M.B. ; RODRIGUES, SILAS PESSINI ; GERALDO, REINALDO BARROS ; KIST,

LUIZA WILGES ; BOGO, MAURICIO REIS ; GONZAGA, LUIZ ; DE VASCONCELOS, ANA TEREZA R ; MORGADO-DÍAZ,

JOSE ANDRES ; ZINGALI, RUSSOLINA BENEDETA ; BENCHIMOL, MARLENE* . New insights on the Golgi complex of

Tritrichomonas foetus. Parasitology (London. Print), v. 14, p. 241-253, 2014. http://dx.doi.org/10.1017/s0031182013001455 *IN

COLLABORATION WITH BENCHIMOL (AL 12)


http://dx.doi.org/10.1002/pmic.201500341


http://dx.doi.org/10.3892/ol.2016.4593


http://dx.doi.org/10.1016/j.joen.2016.02.013

https://doi.org/10.1016/j.urolonc.2015.07.016

http://dx.doi.org/10.1155/2015/313842

http://dx.doi.org/10.1016/j.thromres.2015.05.032



http://dx.doi.org/10.1590/S1677-5538.IBJU.2014.0051

http://dx.doi.org/10.1590/S1677-5538.IBJU.2014.0051


http://dx.doi.org/10.1007/s10142-014-0414-z

http://dx.doi.org/10.1007/s00436-014-4292-z

http://dx.doi.org/10.1016/j.joen.2015.02.006

http://dx.doi.org/10.1186/s13568-015-0102-y

http://dx.doi.org/10.1016/j.ijbiomac.2015.03.071



http://dx.doi.org/10.1017/s0031182013001455


59

5. DE OLIVEIRA, ANDREIA DA SILVA ; YANG, LIKIU ; ECHEVARRIA-LIMA, JULIANA ; MONTEIRO, ROBSON Q. ; REZAIE,

ALIREZA R. . Thrombomodulin modulates cell migration in human melanoma cell lines. Melanoma Research, v. 24, p. 11-19, 2014.

http://dx.doi.org/10.1097/CMR.0000000000000035

6. DOS SANTOS, ALDA E ; KUSTER, RICARDO M ; YAMAMOTO, KRISTIE A ; SALLES, TIAGO S ; CAMPOS, RENATA ; DE

MENESES, MARCELO DF ; SOARES, MÁRCIA R ; FERREIRA, DAVIS . Quercetin and quercetin 3-O-glycosides from Bauhinia

longifolia (Bong.) Steud. show anti-Mayaro virus activity. Parasites & Vectors, v. 7, p. 130, 2014. http://dx.doi.org/10.1186/1756-3305-7-

130

7. FACINCANI, AGDA P. ; MOREIRA, LEANDRO M. ; SOARES, MÁRCIA R. ; FERREIRA, CRISTIANO B. ; FERREIRA, RAFAEL

M. ; FERRO, MARIA I. T. ; FERRO, JESUS A. ; GOZZO, FABIO C. ; DE OLIVEIRA, JULIO C. F. . Comparative proteomic analysis

reveals that T3SS, Tfp, and xanthan gum are key factors in initial stages of Citrus sinensis infection by Xanthomonas citri subsp. citri.

Functional & Integrative Genomics (Print), v. 14, p. 205-217, 2014. http://dx.doi.org/10.1007/s10142-013-0340-5

8. GAZOS-LOPES, FELIPE ; OLIVEIRA, MAURICIO M. ; HOELZ, LUCAS V. B. ; VIEIRA, DANIELLE P. ; MARQUES,

ALEXANDRE F. ; NAKAYASU, ERNESTO S. ; GOMES, MARTA T. ; SALLOUM, NASIM G. ; PASCUTTI, PEDRO G*. ; SOUTO-

PADRÓN, THAÏS* ; MONTEIRO, ROBSON Q. ; LOPES, ANGELA H. ; ALMEIDA, IGOR C. . Structural and Functional Analysis of

a Platelet-Activating Lysophosphatidylcholine of Trypanosoma cruzi. PLoS Neglected Tropical Diseases (Online), v. 8, p. e3077, 2014.

http://dx.doi.org/10.1371/journal.pntd.0003077 *IN COLLABORATION WITH SOUTO-PADRÓN (AL 11)

9. GOMES, LUCIANA DOS SANTOS ; SENNA, RAQUEL ; SANDIM, VANESSA ; SILVA-NETO, MÁRIO ALBERTO CARDOSO DA

; PERALES, JONAS ; ZINGALI, RUSSOLINA BENEDETA ; SOARES, MÁRCIA R. ; FIALHO, E. . Four conventional [Glycine max

(L.) Merrill] soybean seeds exhibit different protein profiles as revealed by proteomic analysis.. Journal of Agricultural and Food

Chemistry, v. 62, p. 1283-1293, 2014. http://dx.doi.org/10.1021/jf404351g

10. GONCALVES, L. R. ; CAMPANHON, I. B. ; DOMINGUES, R. R. ; LEME, A. F. P. ; SOARES, MÁRCIA R . Comparative Salivary

Proteome of Hepatitis B- and C-Infected Patients. Plos One, v. 9, p. e113683, 2014. http://dx.doi.org/10.1371/journal.pone.0113683

11. HIGA, LUIZA M. ; CURI, BRUNO M. ; AGUIAR, RENATO S. ; CARDOSO, CYNTHIA C. ; DE LORENZI, ANDRÉ G. ; SENA,

SILVIA L. F. ; ZINGALI, RUSSOLINA B. ; DA POIAN, ANDREA T. . Modulation of α-Enolase Post-Translational Modifications by

Dengue Virus: Increased Secretion of the Basic Isoforms in Infected Hepatic Cells. Plos One, v. 9, p. e88314, 2014.


12. PEREIRA, PATRÍCIA RIBEIRO ; AGUILA, EDUARDO MERE ; VERÍCIMO, MAURÍCIO AFONSO ; ZINGALI, RUSSOLINA

BENEDETA ; PASCHOALIN, VÂNIA MARGARET FLOSI ; SILVA, JOAB TRAJANO . Purification and Characterization of the

Lectin from Taro (Colocasia esculenta) and Its Effect on Mouse Splenocyte Proliferation In Vitro and In Vivo. The Protein Journal, v. 33,

p. 92-99, 2014. http://dx.doi.org/10.1007/s10930-013-9541-y

13. SOUZA-FERREIRA, PAULA S. ; MOREIRA, MÔNICA F. ; ATELLA, GEÓRGIA C. ; OLIVEIRA-CARVALHO, ANA LÚCIA ;

EIZEMBERG, ROBERTO ; MAJEROWICZ, DAVID ; MELO, ANA C.A. ; ZINGALI, RUSSOLINA B. ; MASUDA, HATISABURO .

Molecular Characterization of Rhodnius prolixus´ embryonic cuticle. Insect Biochemistry and Molecular Biology, v. 51, p. 89-100, 2014.

http://dx.doi.org/10.1016/j.ibmb.2013.12.005

14. WAISBERG, MICHAEL ; MOLINA-CRUZ, ALVARO ; MIZURINI, DANIELLA M. ; GERA, NIDHI ; SOUSA, BEATRIZ C. ; MA,

DONGYING ; LEAL, ANA C. ; GOMES, TAINÁ ; KOTSYFAKIS, MICHALIS ; RIBEIRO, JOSÉ M. C. ; LUKSZO, JAN ; REITER,

KARINE ; PORCELLA, STEPHEN F. ; OLIVEIRA, CARLO J. ; MONTEIRO, ROBSON Q. ; BARILLAS-MURY, CAROLINA ;

PIERCE, SUSAN K. ; FRANCISCHETTI, IVO M. B. . Plasmodium falciparum Infection Induces Expression of a Mosquito Salivary

Protein (Agaphelin) That Targets Neutrophil Function and Inhibits Thrombosis without Impairing Hemostasis. PLoS Pathogens (Online),

v. 10, p. e1004338, 2014. http://dx.doi.org/10.1371/journal.ppat.1004338

AL 4 main publications in 2013: 1. ALMENARA, DANIELA P. ; DE MOURA, JOSELENE P. ; SCARABOTTO, CRISTIANE P. ; ZINGALI, RUSSOLINA B. ; WINTER,

CARLOS E. . The Molecular and Structural Characterization of Two Vitellogenins from the Free-Living Nematode Oscheius tipulae. Plos


2. ANGELO, I. C. ; GOLO, P. S. ; PERINOTTO, W. M. S. ; CAMARGO, M. G. ; COUTINHO-RODRIGUES, C. J. B. ; CAMPANHON, I.

B. ; BRAZ, G. R. C. ; SOARES, M. R. ; FOLLY, E. ; BITTENCOURT, V. R. E. P. . Detection of serpins involved in cellular immune

response of Rhipicephalus microplus challenged with fungi. Biocontrol Science and Technology (Print), v. 24, p. 1-17, 2013.

http://dx.doi.org/10.1080/09583157.2013.863269

3. DE ASSIS, LEANDRO JOSÉ ; ZINGALI, RUSSOLINA BENEDETA ; MASUDA, CLAUDIO AKIO ; RODRIGUES, SILAS PESSINI

; MONTERO LOMELI, MONICA . Pyruvate decarboxylase activity is regulated by the Ser/Thr protein phosphatase SIT4 in the yeast

Saccharomyces cerevisiae. FEMS Yeast Research, v. 13, p. 518-528, 2013. http://dx.doi.org/10.1111/1567-1364.12052

4. DE FIGUEIREDO VILELA, LEONARDO ; DE MELLO, VINICIUS MATTOS ; REIS, VIVIANE CASTELO BRANCO ; BON, ELBA

PINTO DA SILVA ; GONÇALVES TORRES, FERNANDO ARARIPE ; NEVES, BIANCA CRUZ ; ELEUTHERIO, ELIS CRISTINA

ARAÚJO . Functional expression of Burkholderia cenocepacia xylose isomerase in yeast increases ethanol production from a glucose-

xylose blend. Bioresource Technology, v. 128, p. 792-796, 2013. http://dx.doi.org/10.1016/j.biortech.2012.10.014

5. DE PAULA, V.S. ; GOMES, N.S.F. ; LIMA, L.G. ; MIYAMOTO, C.A. ; MONTEIRO, R.Q. ; ALMEIDA, F.C.L. ; VALENTE, A.P. .

Structural Basis for the Interaction of Human β-Defensin 6 and Its Putative Chemokine Receptor CCR2 and Breast Cancer Microvesicles.

Journal of Molecular Biology, v. 425, p. 4479-4495, 2013. http://dx.doi.org/10.1016/j.jmb.2013.08.001

6. FIGUEIRA-MANSUR, J. ; FERREIRA-PEREIRA, A. ; MANSUR, J. F. ; FRANCO, T. A. ; ALVARENGA, E. S. L. ; SORGINE, M. H.

F. ; NEVES, B. C. ; MELO, A. C. A. ; LEAL, W. S. ; MASUDA, H. ; MOREIRA, M. F. . Silencing of P-glycoprotein increases mortality

in temephos-treated Aedes aegypti larvae. Insect Molecular Biology (Print), v. 22, p. 648-658, 2013. https://doi.org/10.1111/imb.12052

7. FRATTANI, F. S. ; WERMELINGER, L.S. ; LOBO, T. C. ; MONTEIRO, R. Q. ; ZINGALI, R. B. . Avaliação da Atividade Plaquetária

em Agregômetro Óptico.. In: Monica Montero-Lomeli; Franklin David Rumjaneck. (Org.). Técnicas em Biociências Protocolos

Comentados para o Laboratório. 1ed.Rio de Janeiro: Medbook, 2013, v. , p. 261-264. [BOOK CHAPTER]

8. GERALDO, RB ; LOPES PCC ; RODRIGUES, C. R. ; Zingali, R.B. ; CASTRO, H.C. . Structural features in neuropsin as potential target

for pharmacological inhibition in brain diseases. International Journal of Biochemistry and Biotechnology, v. 2, p. 302, 2013.

https://www.researchgate.net/publication/255991180

9. LIMA, LUIZE ; MONTEIRO, ROBSON . Activation of blood coagulation in cancer: implications for tumor progression. Bioscience

Reports, v. 33, p. e00064, 2013. http://dx.doi.org/10.1042/BSR20130057

10. LIMA, LUIZE G. ; LEAL, ANA CAROLINA ; VARGAS, GABRIELA ; PORTO-CARREIRO, ISABEL ; MONTEIRO, ROBSON Q. .

Intercellular transfer of tissue factor via the uptake of tumor-derived microvesicles. Thrombosis Research, p. 450-456, 2013.


11. LIMA, LUIZE G. ; MEIS, E. ; MONTEIRO, R.Q. . Distúrbios Trombóticos no Câncer. In: Artur Katz; Roger Chammas; Yana S. Novis;

Vicente O. Filho. (Org.). Tratado de Oncologia. 01ed.São Paulo: , 2013, v. 01, p. 419-430. [BOOK CHAPTER]

12. LOBO, T. C. ; FRATTANI, F. S. ; WERMELINGER, L.S. ; MONTEIRO, R. Q. ; Zingali, RB . Avaliação dos Complexos da Coagulação

Sanguínea. In: monica Montero-Lomeli; Franklin David Rumjaneck. (Org.). Técnicas em Biociências Protocolos Comentados para o

Laboratório. 1ed.rio de Janeiro: medbook, 2013, v. , p. 258-260. [BOOK CHAPTER]

13. MA, D. ; Mizurini, D. M. ; Assumpcao, T. C. F. ; LI, Y. ; QI, Y. ; Kotsyfakis, M. ; RIBEIRO, J. M. C. ; MONTEIRO, R. Q. ;

FRANCISCHETTI, I. M. B. . Desmolaris, a novel Factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus

rotundus) inhibits inflammation and thrombosis in vivo. Blood (Philadelphia, PA), v. 122, p. 4094-4106, 2013.

http://dx.doi.org/10.1182/blood-2013-08-517474

14. MELO, A. C. A. ; OLIVEIRA, D. S. ; FRANCO, T. A. ; NUNES, A. T. ; XU, P. ; CARDOSO, M. F. M. C. ; SOARES, M. R. ; LEAL,

W. S. . Multidisciplinary approaches to molecular basis of olfaction in Rhodnius prolixus and Aedes aegypti. Pathogens and Global

Health, v. 107, p. 406-407, 2013. http://dx.doi.org/10.1179/2047772413Z.000000000160

15. MIZURINI, DANIELLA M. ; FRANCISCHETTI, IVO M.B. ; MONTEIRO, ROBSON Q. . Aegyptin inhibits collagen-induced

coagulation activation in vitro and thromboembolism in vivo. Biochemical and Biophysical Research Communications (Print), v. 436, p.

235-239, 2013. http://dx.doi.org/10.1016/j.bbrc.2013.05.082

http://dx.doi.org/10.1097/CMR.0000000000000035

http://dx.doi.org/10.1186/1756-3305-7-130

http://dx.doi.org/10.1186/1756-3305-7-130

http://dx.doi.org/10.1007/s10142-013-0340-5


http://dx.doi.org/10.1021/jf404351g



http://dx.doi.org/10.1007/s10930-013-9541-y


http://dx.doi.org/10.1371/journal.ppat.1004338


http://dx.doi.org/10.1080/09583157.2013.863269

http://dx.doi.org/10.1111/1567-1364.12052

http://dx.doi.org/10.1016/j.biortech.2012.10.014


https://doi.org/10.1111/imb.12052

https://www.researchgate.net/publication/255991180

http://dx.doi.org/10.1042/BSR20130057


http://dx.doi.org/10.1182/blood-2013-08-517474

http://dx.doi.org/10.1179/2047772413Z.000000000160

http://dx.doi.org/10.1016/j.bbrc.2013.05.082


60

16. PEREIRA, ALYSON G. ; PACHECO, GRAZIELA J. ; TAVARES, LUIZ F. ; NEVES, BIANCA C. ; KRONEMBERGER,

FREDERICO DE A. ; REIS, RODRIGO S. ; FREIRE, DENISE M.G. . Optimization of biosurfactant production using waste from

biodiesel industry in a new membrane assisted bioreactor. Process Biochemistry (1991), v. 48, p. 1271-1278, 2013.


17. PROVENZANO, J. C. ; SIQUEIRA JR, J. F. ; ROCAS, I. N. ; LEME, A. F. P. ; SOARES, M. R. . Metaproteome Analysis of Endodontic

Infections in Association with Different Clinical Conditions. Plos One, v. 8, p. e76108, 2013.


18. ROCHAEL, NATALIA CADAXO ; LIMA, LUIZE GONCALVES ; OLIVEIRA, SANDRA MARIA PEREIRA DE ; BARCINSKI,

MARCELLO ANDRE ; SARAIVA, ELVIRA MARIA ; MONTEIRO, ROBSON QUEIROZ ; PINTO-DA-SILVA, LUCIA HELENA .

Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva.

Memórias do Instituto Oswaldo Cruz (Impresso), v. 108, p. 679-685, 2013. http://dx.doi.org/10.1590/0074-0276108062013002

19. TAVARES, LUIZ F. D. ; SILVA, PATRÍCIA M. ; JUNQUEIRA, MAGNO ; MARIANO, DANIELLY C. O. ; NOGUEIRA, FÁBIO C.

S. ; DOMONT, GILBERTO B. ; FREIRE, DENISE M. G. ; NEVES, BIANCA C. . Characterization of rhamnolipids produced by wild-

type and engineered Burkholderia kururiensis. Applied Microbiology and Biotechnology, v. 97, p. 1909-1921, 2013.

http://dx.doi.org/10.1007/s00253-012-4454-9

20. VIEIRA, S. M. ; DOS REIS, F ; GERALDO, R ; DUTRA, D. L. S. ; JULIANO, L. ; JULIANO, MA ; MIGNACO JA ; ZINGALI, R.B. .

Investigation of Thrombin Activity with PAR 1-based Fluorogenic Peptides. Protein and Peptide Letters, v. 20, p. 1129-1135, 2013.

http://dx.doi.org/10.2174/09298665113209990001

21. VILLA, ANA LÚCIA ; ARAGÃO, MÁRCIA REGINA ; DOS SANTOS, ELISABETE PEREIRA ; MAZOTTO, ANA MARIA ;

ZINGALI, RUSSOLINA B ; DE SOUZA, EDILMA PARAGUAI ; VERMELHO, ALANE BEATRIZ . Feather keratin hydrolysates

obtained from microbial keratinases: effect on hair fiber. BMC Biotechnology (Online), v. 13, p. 15, 2013. http://dx.doi.org/10.1186/1472-

6750-13-15

22. WERMELINGER, L.S. ; LOBO, T. C. ; FRATTANI, F. S. ; MONTEIRO, R. Q. ; ZINGALI RB . Testes para Avaliação de Hemostasia.

In: Monica Montero-Lomeli; Franklin David Rumjaneck. (Org.). Técnicas em Biociências Protocolos Comentados para o Laboratório.

1ed.Rio de Janeiro: Medbook, 2013, v. , p. 253-257. [BOOK CHAPTER]



http://dx.doi.org/10.1590/0074-0276108062013002

http://dx.doi.org/10.1007/s00253-012-4454-9

http://dx.doi.org/10.2174/09298665113209990001

http://dx.doi.org/10.1186/1472-6750-13-15

http://dx.doi.org/10.1186/1472-6750-13-15


61

AL 5 - Associate Laboratory of Nuclear Magnetic

Resonance, Organic Synthesis and Molecular Modeling

- Coordinator:

José Daniel Figueroa Villar - IME.


Claudia Jorge do Nascimento, Universidade Federal do Rio de Janeiro;

Josane Lessa, Universidade Estadual do Rio de Janeiro;

Marilza Batista Correa, FIOCRUZ.


Elaine da Conceição Petronilho (IME),

Sirlene Oliveira Francisco de Azeredo

(IME),

Denise Cristian Ferreiro Neto (IME),

Edijane Matos Sales (IME),

Jacqueline Santos Cruz (IME),

Juliana de Oliveira Carneiro Brum (IME),

Diego Arantes Teixeira Pires (IME e UNB),

Ingrid Eduarda de Sousa Lima (IME),

Jenilce Ribeiro Martins (IME).


Mariana de Oliveira Tonelli (IME),

Luana Gonçalves de Souza (IME),

Rômulo Santiago de Lima Gracia (IME),

Priscila Ivo Rubim de Santana (IME),

Eduardo Miranda da Silva Mangefeste

(IME),

Beatriz Ferreira Moura (IME), Paulo Cézar

Prado (IME),

Camila Capelini Cámara (IME)

Beatriz Ferreira Moura (IME).


Julia Zimmermann (IME)

“INBEB is a very efficient research group, which I consider very important. About

obtaining better results with our research group on the Military Institute of Engineering (IME),

is necessary the participation of other member of INBEB, specially by production of enzymes to

be tested as inhibition or reactivation by NMR and the process of biological tests of the

synthesized potential pharmacological agents from our group. We also need some resources to

acquisition of materials for synthesis and solvents by NMR, as well as one equipment for

efficient purification of new materials. We are also available to help the other INBEB research

groups on our topics of work, as quantum mechanics, spectroscopy, synthesis, molecular

modeling and docking."

- Professor José Daniel Figueroa Villar

1- DESIGN, SYNTHESIS,

STRUCTURE DETERMINATION AND

STUDY OF THEIR INTERACTION

AND INHIBITION WITH THE

ENZYME

ACETYLCHOLINESTERASE BY

NUCLEAR MAGNETIC RESONANCE

(NMR) AS POTENTIAL DRUGS FOR

ALZHEIMER'S DISESE

The project being developed aims to

synthesis and study the interaction of new

drugs with biomolecular targets by Nuclear

Magnetic Resonance (NMR). In the

interaction study, the aim was to study the

kinetics and inhibition of these targets

biomolecular pharmaceuticals, using the

NMR technique.

They will be used as a biomolecular targets

some enzymes, and fragments of

deoxyribonucleic acid (DNA), called

oligonucleotides. One of these is the

enzyme acetylcholinesterase (AChE),

which is important both for public health as


62

the study for defense against chemical

warfare. Another enzyme to be used is

dihydrofolate reductase (DHFR), which is

used as a therapeutic target for various

infectious diseases.

It has recently been developed by our

research group a relatively simple method

for the determination of enzyme inhibition

by NMR and that can be used with many

biological targets (Soares et al., 2013),

which will be used and enhanced during

this job.

The intermolecular interactions between

ligands and receptors are part of the

macromolecular most biological processes

(Otting 1993). In general, the biological

function of a protein depends on its

interaction with ligands, and these links

crucial to maintain the high degree of order

of a living system (GOLAN et al, 2009).

Can be cited as examples: the interaction

between hormone receptors with hormones;

the interaction of proteins with certain

nucleic acids, genes that regulate

replication, transcription or translation; or

the highly specific interaction between

antigens of the cell surface receptors

located in other cells. There are many

examples given amount of biological

processes in which the proteins are

involved (Meyer; Peters, 2003).

The functions of many proteins involve

reversible binding with other molecules. A

molecule that binds to a protein ligand is

called. A binder may be any type of

molecule, including another protein. A

binder is combined at a particular site in the

protein called binding site which is

complementary to the size, shape, charge,

hydrophobic or hydrophilic character

suitable for interaction (Lehninger, 2007).

The connection is governed by the

complementary shape of the molecule that

binds to the protein as well as governed by

polar, ionic interactions, hydrogen bonding

interactions π-stacking and other processes

that are established between the protein and

ligand (MURAY 2007).

Understanding the biological function

requires a precise study of interactions

between the atomic-level protein-ligand.

The study of physical and chemical

phenomena triggered by intermolecular

interactions between ligands and

macromolecular receptors are the key to

understanding the various biological

processes (Otting, 1993). Therefore, it has

sought to develop accurate biophysical

methods for the characterization of these

processes.

The Nuclear Magnetic Resonance (NMR)

has become an important technique in the

study of protein-ligand interactions, being

able to detect and quantify interactions with

a good sensitivity without prior knowledge

of protein function (Meyer; Peters, 2003).

In recent years, research has been carried

out using NMR techniques to elucidate and

understand better the process of protein-

ligand binding to molecular level, and thus

use this information to the discovery of new

bioactive substances (Meyer; Peters, 2003).

The hydrogen NMR (1H NMR) is a

technique that requires little or no treatment

of the sample is fast, robust, reproducible,

quantitative and non-destructive. The

development of the NMR in the higher

magnetic fields, and in the development of

different multidimensional techniques, have

enabled a higher spectral simplification.

The study of protein-ligand interactions by

NMR can be done by mapping the chemical

shifts of the macromolecules and binders.

To observe the macromolecules is

necessary isotopic and 3D experiments

marking. In general, proteins should have a

molecular weight (MW) <50 kDa are

observed by NMR.

When it has proteins with high molecular

mass, it becomes necessary follow these

interactions through the properties of the

binders because they are smaller molecules,

they generate simplest NMR spectra are

interpreted.

NMR experiments such as measurements of

the relaxation times T1 and T2, STD

(saturation transfer difference) (Meyer &

Peters, 2003), WaterLOGSY (Water Ligand

Observation with Gradient Spectroscopy),

nuclear Overhauser effect (NOE) and

diffusion coefficients (DOSY ) are

examples of methods that will be used for

molecular interaction studies.

The proposed study will be conducted in

Nuclear Magnetic Resonance Laboratory of

the Military Engineering Institute (IME), in

Rio de Janeiro, under the guidance of

Professor PhD. José Daniel Figueroa Villar

(IME) and co-supervision of Professor D.Sc

Claudia Jorge Nascimento (UNIRIO). Prof.

Research Group Figueroa-Villar has


63

expertise in Nuclear Magnetic Resonance

area (NMR).

This laboratory has a spectrometer Agilent

600 MHz equipped with all the hardware

and software required to perform the

experiments. All solvents, reagents and

glassware used for the experiments are

available in Nuclear Magnetic Resonance

Laboratory and the Laboratory of Medicinal

Chemistry of the EMI group, coordinated

by Prof. Figueroa-Villar.

The compounds to be used as ligands will

be synthesized and provided by the EMI

Medicinal Chemistry research group,

coordinated also by Prof.. Figueroa-Villar.

Evaluation studies by kinetic spectroscopy

UV-Vis will be held in Molecular

Pharmacology Laboratory of the Institute of

Biological Sciences, Federal University of

Rio de Janeiro - UFRJ. The equipment used

is a spectrophotometer microplate reader

Spectra Max 250 Molecular Brand

Devices®.

It is expected to result in the execution of

this project the understanding of the

interaction, molecular dynamics, and

inhibition kinetics of drugs with

biomolecular targets: using different

activities, correlating the intermolecular

interaction with the biological activity of

the substance. Also seek to develop new

methodology for interaction studies, based

on the results obtained. Dissemination of

research results through the development of

scientific research work, publication of the

results in national and / or international

indexed journals; participation in seminars

and national conferences with presentation

of the results. Thus, we intend to optimize

the design of new and more efficient drugs.

PRELIMINARY RESULTS During the first and second period 2014, it

was performed literature review and

completion of the doctoral thesis proposal.

The defense of the proposal took place on

October 12, 2014 before a bank examiner

with an internal member of the IME and an

external member (UFRJ).

There were synthesized 25 new compounds

with potential action for Alzheimer's

disease.

It was conducted some laboratory tests

concerning the thesis and with these results,

it was possible to participate in the XII

Brazilian Conference Nuclear Magnetic

Resonance with paper presentation as a

poster. The student also participated in the

preparation of a work that was submitted to

the VII Biennial Meeting of the Nuclear

Magnetic Resonance in Alcalá de Henares -

Spain.

During the third quarter of 2014 the

selection was made of the compounds to be

used in the thesis. two compounds were

selected initially, having been held

solubility tests on the means necessary to

perform the tests. Subsequently, it was

performed the test enzyme kinetics by

NMR. This enzyme kinetics methodology

by NMR was developed by our research

group (Soares et al., 2013) and basically

consists in determining the enzyme's ability

studied to process its natural substrate when

exposed to inhibitory conditions that

prevent access to your site active. The

kinetic evaluation tests are carried out by

NMR AChE acetylcholinesterase enzyme,

which is the enzyme that catalyzes this

process into synapses in the central nervous

system. Yielded significant results with the

samples. The selected samples seek to be

used in the treatment of Alzheimer's disease

(AD), so it has a structural similarity to

Tacrine, which is the most efficient

inhibitor which acts on the AD. However,

this inhibitor has a high hepatotoxicity. For

this reason, seek to be more efficient drugs

and they do not have this contraindication.

In perspectives to improve this

methodology is intended to include self-

shimming previously obtain each spectrum

(each 5 min) and improve procedures for

more appropriate integration in all cases, as

well as changes in agent concentrations,

temperature and introduction of substrate.

FIG. 1 is shown a simplified schematic of

hydrolysis of acetylcholine by the enzyme,

which verifies that the substrate

acetylcholine generates products: acetic

acid (or acetate due to the aqueous medium)

and choline.

FIG. 1 Simplified scheme of hydrolysis of

acetylcholine.

The kinetic evaluation by NMR is to

monitor two species in particular:

acetylcholine and acetate, more particularly

the methyl groups of each (FIG. 2). This is


64

because their methyl groups appear in

clean, distinct regions, but close, and as

simpletos in the 1H NMR spectrum.

Because of the stoichiometric ratio for each

mole of acetylcholine it disappears from the

reaction medium, there arises a mole

acetate, which makes the integration of the

signals of the two species is

straightforward.

FIG.2 Species Monitored by 1H NMR.

In FIG.3 is shown the reaction occurring in

the NMR tube and the species behavior. In

this example, measurements were taken

every 5 min (17 in total) for a total of 1h 20

min experiment. The left peak (2.02 ppm)

match the signal of methyl group of

acetylcholine (decreases) and the peaks to

the right (1.78 ppm) of the methyl group

signal acetate (increases).

FIG. 3 Evolution of acetylcholine hydrolysis

Reaction monitored by 1H NMR.

In the next period, we intend to select other

samples for both kinetic tests as well as the

NMR interaction tests. It is also intended to

present the initial results in Congress at the

beginning of 2015.

They were performed this semester docking

studies, synthesis, characterization and

enzyme kinetics tests by Ellman and

Nuclear Magnetic Resonance (NMR) of the

eight compounds selected for this study

(TAB. 1). Yet an analysis was performed of

the structure-activity through theoretical

methodology for predicting

physicochemical properties and toxicity in

silico.

TAB. 1 Example with the Spartan program

structures 6 'of the molecules used in the study.

In molecular modeling tests of the

compounds studied were presented as

potential candidates for the treatment of

Alzheimer's disease, and according to the

docking the most promising compounds

would be: 9, 10, 15 and 16, as showed

binding energy, and the intermolecular

energy more stable and also set lower than

the theoretical inhibition of tacrine. This

indicates a good selectivity of these

complexes in relation to other evaluated

compounds, indicating a good chance of

AChE. It was realized that these

compounds interact with the aminoacid

residue His440 (present in the catalytic


65

triad), and this interaction is important for

preventing the hydrolysis of ACh substrate.

These compounds also held interaction with

Trp84 (present in the catalytic cavity) that

has been used in many other studies of

molecular docking as an important marker

of inhibition.

The synthesized compounds showed good

yields (75-80%), and the compounds 15 and

16 are unpublished.

The test results of AChE by Ellman and

NMR showed the compound 9 has the

highest inhibitory capacity with a

percentage of inhibition greater than 93%,

is compatible with the target data.

Compounds 10:12 also showed good

inhibitory ability, about 89-92% in both

tests. The compound 10 also showed good

inhibition of prediction by molecular

modeling. Since the compound 12 by

modeling showed high inhibition constant,

which indicates that this compound would

not be a good inhibitor but also by molding

the compound made interactions with

Hiss440 and Trp84 residues that are

important interactions and were probably

decisive in the good value of experimental

inhibition (89.77% by Ellman and 81.76

NMR) presented.

Based on the data obtained in inhibition

tests by IR and NMR could be seen that the

NMR technique is valid to study the

inhibition of compounds with biological

targets as presented approximate values to

those presented by the Ellman test.

Regarding the calculation of

pharmacokinetic and toxicological

properties of compounds studied, all fall

within the parameters outlined in Rule Five,

and because of this, are promising to make

a good oral bioavailability and penetration

of the central nervous system. Regarding

toxicological results suggest that the

compounds showed low level for:

tumorigenicity, mutagenicity and irritative

effects. It is noteworthy that compared the

effects on the reproductive system, with the

exception of the compound 10, which had

an average risk, the other also had low risk.

It is necessary to conduct biological tests in

vitro and in vivo with the best inhibitors to

confirm the pharmacokinetic and

toxicology results.

Thus, the work presented to date,

interesting results for inhibitory compounds

of the AChE enzyme and potential drugs

for the treatment of AD, and necessary

analyzes to study the process of interaction

of these compounds with the target enzyme.

So it will be done by NMR study of

interaction of these compounds with AChE

enzyme to better assess the interaction

processes taking place.

With the results obtained so far been

possible to present the qualification thesis

on August 21, 2105, having been approved

student. also it was presented work in

Nuclear Magnetic Resonance 15TH Users

Meeting, Angra dos Reis in August 2015.

The NMR inhibition of AChE from some

of the new compounds synthesized is

shown on Table 2, a process that indicates

one compound most effective than tacrine

and others with good activity.

TAB 2 Results of AChE inhibition of 9 new agents

and tacrine

With these results is confirmed that the new

planed and synthesized compounds are

good for Alzheimer's disease.

Outlook for the next period: • Design, synthesis and complete structure

determination of new potential agents for

ad;

• Molecular dynamics study of the best

inhibitor compounds;

• Realization of NMR interaction tests

with the selected compounds;

• Conduct biological tests in vitro and in

vivo with the best inhibitors.

2-SYNTHESIS AND STUDY BY

NUCLEAR MAGNETIC RESONANCE

AND NMR NOVEL DERIVATIVES OF

4 OXOQUINOLONAS AS POTENTIAL

INHIBITORS OF NUCLEOSIDE

HYDROLASE FOR LEISHMANIASIS

AND ANTIBIOTICS.


66

Neglected diseases correspond to a group of

infectious diseases that predominantly

affect poor populations, being a global

public health problem (WERNECK et al,

2011). However, pharmaceutical companies

are driven by the private industrial sector to

focus research on diseases where the drug

can be produced and sold more profitably

(Brenan et al, 2007). With this, the least

developed countries live with tropical

diseases without effective treatment such as

malaria, tuberculosis, leprosy,

schistosomiasis, Chagas disease,

leishmaniasis and other (MS, 2010).

For the production of a new prototype for

the treatment of leishmaniasis is studies for

the inhibition of nucleoside hydrolase. This

enzyme is not found in mammals and some

studies indicate that this may be an

important blocking the biological cycle of

the parasite (Herwaldt et al, 1999). Reports

in the literature two nucleoside hydrolase

inhibitors by kinetic study showed

promising results as option strategy for the

production of a new drug (RENNÓ et al,

2012).

The class of quinolones is an expectation

for the production of pharmaceuticals

having characteristics for inhibiting

nucleoside hydrolase enzyme (RENNÓ et

al, 2012). Currently, the main application of

this class is for microbial action because of

its potential against a broad spectrum of

bacteria than other classes of antibiotics

(Owens et al, 2005). Therefore presents

quinolones as an interesting class, as it has

great potential for development through

simple synthetic routes and known in the

literature as the method of etilenomalonico

ester by method of Grohe-Heitzer (Gould et

al, 1939; GROHE et al, 1946; MITSCHER,

2005).

The type of compound is initially planned

shown in Figure 1, in which knowledge of

the amino acid residues present at the active

site of the enzyme through molecular

modeling, shows types of interaction can

with NH. The compound was planned as a

function of the site in which the acetyl

group is required to interact with aspartic

acid, a di-hydroxyl is essential for

interaction with Ca2 +, the carboxyl group

that is in anionic form, interacts with

arginine and the aromatic ring makes

interaction π-stacking type with tyrosine

(RENNÓ et al, 2012). This compound, in

di-hydroxy system does not have capacity

to be hydrolyzed and should provide greater

stability.

Fig. 1 Model of possible new compound to

inhibition of NH.

The first step in the method consists of

ethylene malonic ester developed by Gould

et al (1939) to obtain 4-oxoquinolonas. The

compounds were prepared via the Michael

addition mechanism / elimination of

substituted anilines and diethyl

etoxietilenomalonato of ethanol under

stirring and reflux giving the product as the

enamine derivative (2 - [(phenylamino)

methylene] -malonatos of diethyl) (Fig.

two). The reaction generated quinolones

with an ester group at position 3 of the ring,

and another substituent at the 6, 7 or 8.

Fig. 2 Synthesis to obtain the enamine derivatives

The next step was carried out cyclization of

the intermediate using Dowtherm® A under

stirring and reflux at 250 ° C in about 30

min., And purify in dimethyl formamide

(DMF) to obtain the 4-oxoquinolonas

derivatives (Fig. 3) ( Gould et al, 1938;

RIEGEL et al, 1946; CANUTO et al, 2007;

LIMA, 2012).

Fig. 3 - Synthesis of obtaining the derivatives of 4-

oxo quinolones

The next step is to use the derivative

obtained from 4-oxoquinolonas to perform

a structural change by performing an N-


67

alkylation to obtain novel compounds using

the method of El Ashry et al (1999). This

procedure will be used DMF, sodium

hydride (NaH) and (±) -2,2-dimethyl-4-

(toluenesulfoniloximetil) -1,3-dioxolane

(tosylated solketal) with heating and

stirring, and the ethyl esters thus obtained

will be acid 1 - ((2,2-dimethyl-1,3-

dioxolan-4-yl) methyl) -1,4-dihydro-4-

oxoquinoline-3-carboxylic acid (Fig.4).

Fig.4 Síntese para obtenção de novas

oxoquinolonas N-alquiladas

The synthetic route planned further

performed to obtain nucleoside hydrolase

inhibiting compounds. Thus, new

derivatives are obtained unpublished 4-

oxoquinolonas based on retrosynthesis (Fig.

5).

Fig. 5 Scheme end of the reactions planned to

obtain new derivatives of 4-oxoquinolonas

Results Until now, the following results were

obtained: It was possible to synthesize,

purify and characterize the enamine

derivatives in good yields by NMR

technique, Tables 1 and 2.

TAB 1 Yield of enamine derivatives

TAB 2 Yield of 4-oxoquinilines

MICROBIOLOGICAL TEST The methodology used in this study was

micro serial dilutions in 96 well plates. In

this in vitro assay allowed quantitatively

analyze the activity of a potential

antimicrobial compound.

The tests were performed in duplicate to

ensure reliability of the results and were

used three different methods for quality

control (positive control, negative and

sterility). The negative control was used the

antibiotic chloramphenicol, which has a

broad spectrum of action. The positive

control was adopted in order to ascertain

the viability of the microorganisms used in

the test. The sterility control was used in

this case to verify the sterility of the culture

medium and also to check the non-

interference of the solvent DMSO which

was used to solubilize the compounds.

Were used antibacterial tests with 5

intermediate compounds and 5 compounds

quinoline derivative synthesized in this

work. In the Table 3 are the results of the

bioactivity of test compounds front of

Gram-negative and Gram-positive bacteria


68

TAB 3 antibacterial screening of the synthesized

compounds

Through the data mentioned above, we can

see that the compounds 1b, 1c, 1f and 2b

showed no inhibition front of the bacteria

tested. The compound showed a better

result S13 inhibition on the bacteria P.

aeruginosa and S. aereus (CIM 250 ug /

ml). Compounds 1a, 1d, 2a, 2d and 2g no

significant inhibition results.

Next steps Syntheses of compounds designed the third

and fourth stage of the reactions and

perform enzyme expression to make the

kinetic studies of enzyme inhibition of

nucleoside hydrolase of Leishmania

chagasi.

3-SYNTHESIS, STRUCTURE

DETERMINATION AND

EVALUATION OF NEW

DERIVATIVES FROM

PHENANTHRENEQUINONE AS

POTENTIAL DRUGS.

The student is studying for a PhD in

chemistry at the Military Institute of

Engineering, and his thesis project based on

the achievement of synthesis of new

derivatives of 9,10-phenanthrenequinone.

Introduction Over the years, 9,10-phenanthrenequinone

(1) has been used for the synthesis of

various compounds which in turn has

presented several biological activities.

Among the classes of compounds present in

these derivatives of 9,10-

phenanthrenequinone we can cite:

thiosemicarbazones, semicarbazones, 1,2,4-

triazines, guanyl hydrazone, diamines,

among others.

These classes of compounds are extremely

important because they are related to

activities such as antioxidant, anticancer,

antibacterial, among others.

So, with so many biological activities

related to these analogues, sparked interest

in our research group to synthesize and

evaluate the biological activity of new

compounds derived from 9,10-

phenanthrenequinone that may be potential

drugs. In particular the class of guanyl

hydrazones and oximes which is already

being studied by our medicinal chemistry

group.

The 9,10-phenanthrenequinone (1) (Fig. 1)

is a 1,2-dicarbonilado compound which

allows a large number of chemical

reactions, such as:. Electrophilic aromatic

substitution (Bhatt 1964) and condensation

(ARORA et al, 2011). And is therefore an

excellent starting material in an attempt to

prepare new substances relatively simple

bioactive.

FIG. 1. Structure of 9,10-phenanthrenoquinone

(1)

Methodologies and results The first step of this work consists in

electrophilic aromatic substitution reactions

in 9,10-phenanthrenequinone (1) by various

groups and eletroatratores eletrodoadores,

among which are: nitro, amino and

halogens (FIG. 2). Then the compounds are

condensed substituted with various groups

such as aminoguanidine hydrochloride,

diamines compounds, thiosemicarbazides

and semicarbazides, inter alia.

FIG. 2. Reaction scheme derivatives of 9,10-

phenanthrenequinone (1)

All the compounds synthesized have been

fully characterized by melting point,

infrared and nuclear magnetic resonance.

After the synthesis and complete structural

elucidation of the compounds, the

bioactivity tests for the determination of a

possible antibiotic activity against Gram-

positive and Gram-negative bacteria will be

realized, their antiprotozoal activity against

Trypanosoma cruzi, Leishmania

amazonensis, Plasmodium falciparum and

its potential to act as intercalators of DNA

by NMR.


69

Derivatives of 9,10-phenanthrenequinone

without substituents were synthesized as

shown in the reactions of Figure 3 with its

respective yields obtained.

FIG. 3. Derivatives from 9,10-

phenanthrenoquinone ( 1)

The first functionalization reaction of 9,10-

phenanthrenequinone (1) was brominated

product as that generated the 3,6-

dibromofenantrenoquinona (2) was used as

starting material for the synthesis of the

following classes of compounds: guanyl

hydrazone, thiosemicarbazone ,

semicarbazone and 1,2,4-triazine, as shown

in Figure 4 and the respective yields

obtained.

FIG. 4. Derivatives from 3,6-

dibromophenanthrenoquinone (2)

The second functionalization reaction of

9,10-phenanthrenequinone (1) was

chlorination using trichloroisocyanuric acid

(11) (FIG. 5). This methodology for the

chlorination of compound 1 is novel and

has been adapted for use by Mendonca et

al, 2005 for the chlorination of compounds

with deactivated rings.

FIG. 5. Chemical Structure of

trichloroisocyanuric acid (11)

The chlorination reaction of 9,10-

phenanthrenequinone (1) allowed the

formation of dichloro compounds (12) and

triclorado (13), as shown in Figure 6. These

compounds are still in phase separation.

After separation will be given further to

obtain the class guanyl hydrazones

compounds thiosemicarbazones,

semicarbazones and 1,2,4-triazines, which

are objectives of this work.

FIG.6. Chlorination reaction of 9,10-

phenanthrenequinone (1)

4-SYNTHESIS AND EVALUATION OF

POTENTIAL NEW DRUGS DERIVED

FROM BARBITURATE AND

SIMILAR BENZYLIDENE.

Barbiturates or barbiturilidenos benzylidene

are important family members pyrimidine

(Khan et al, 2011). The greatest importance

in this class of compounds is focused on

their use as precursors in the preparation of

new and more complex heterocyclic

compounds (Sweidan et al, 2011) as

diaminopyrimidines, furopirimidinas and

piranopirimidinas FIGUEROA-VILLAR et

al, 1992), oxadeazaflavinas (FIGUEROA-

VILLAR & CRUZ, 1993; FIGUEROA-

VILLAR & OLIVEIRA, 2011) and

barbiturates (Vieira et al, 2011).


70

The structure of the barbiturate benzylidene

is characterized by strong double bond

exocyclic polarized with a partial positive

charge on the arylidene carbon. This

polarization of the double bond facilitates

the nucleophilic attack on the carbon, which

makes these compounds are widely used in

reactions with active methylenes groups

with Isonitriles or zinc organometallic

reagents (SEELIGER et al, 2007). In view

of the wide application of this class of

compounds, this study aimed to synthesize

heterocyclic compounds using benzylidene

barbiturate and the like as intermediaries to

obtain compounds with potential

bioactivity.

Methods and Results In this paper three different groups were

synthesized derivatives and analogs

benzylidene barbiturate compounds:

1. Guanylhydrazones;

2. Furo [2,3-d] pyrimidine;

3. Condensation of compounds with

amino-benzaldehyde

Synthesis of guanylhydrazones The synthesis of hydrazones guanylyl

consists of 3 steps. The first step is the

Knoevenagel condensation between

aromatic aldehyde and dimedone followed

by a Michael addition tetracetonas forming.

Then the tetracetona is cyclized using p-

toluenesulfonic acid forming

xantenodionas. The last step is the

hydrazone formation by reacting guanyl

xantenodiona of aminoguanidine

hydrochloride as shown in Figure 1.

FIG 1. Synthesis of guanylhydrazones

All intermediates and final compounds

were characterized by melting point, IR,

NMR and mass spectra. The compounds of

the first stage (tetraketones) were obtained

in excellent yields (80-94%) as well as

compounds which were cyclized

(xanthenediones) in the second reaction

stage (83-96%). The guanylhydrazones

were obtained with good yields and all

guanylhydrazones synthesized are

unprecedented. These compounds will be

tested as antibacterial and antifungal.

Studies of molecular modeling and NMR To determine the conformational structure

of triketones (compounds synthesized in

step 1) studies were conducted by NMR

and molecular modeling. From the results

of NMR and molecular modeling was

possible to confirm the presence of two

links of intramolecular hydrogen. The

theoretical and experimental results have

shown that the conformational

interconversion these molecules occurs by

rotation of the benzene ring and light

movement of dimedone ring, leading to

variation in the length of intramolecular

hydrogen bonding, as shown in Figure 2.

FIG 2. Hydrogen ligation signals from compounds

with p-methoxi substitution and conformational

exchange suggested by the rings movement from

dimedone of tetraketones with para groups

The presence of a substituent at the ortho

position of the benzene ring conformational

changes the interconversion, leading to the

disappearance of an intramolecular

hydrogen bond and overlapping of several

NMR signals. The correlation of the sp

values with chemical shifts, angles and

atomic charges confirms that the electronic

properties of the R-for groups are involved

in conformational changes and variation in

the chemical shifts. To illustrate, in Figure

3 shows the 13C NMR spectra of

compounds with the nitro group in the para

position and disubstituted in the ortho

position and in which we can observe the


71

spectra of overlapping signals CH2 and

CH3

FIG 3. Comparison of the CH2 and CH3 signals

from the 13C NMR spectra of compounds with the

nitro group on the para position and bis-

substituted on the orto e para position.

Therefore, with the use of molecular

modeling and NMR data, with an emphasis

on NOESY, HSQC and HMBC, it was

possible to obtain the definitive assignment

signal and the three dimensional

conformation for all compounds. An

example is the most stable three-

dimensional structure of the compound p-

nitro group as shown in Figure 4.

FIG 4. Three-dimensional structure of the

compound indicated with the p-nitro group. 1H

13C red and blue. (But signs marked * may be

exchanged)

These results will be used to study the

interaction of these compounds with

biomolecules and their use as starting

materials in the design and synthesis of

novel bioactive compounds.

Test of inhibition / activation of the

enzyme tyrosinase Tyrosinase is the enzyme responsible for

melanin production, however, the

occurrence of melanoma, which is one of

the most serious form of skin cancer, may

be associated with this disorder this enzyme

(Chang, 2009). Therefore, it is important to

develop tyrosinase inhibitors for the

treatment of skin cancer.

NMR was possible to discover that some of

the tetrahydrofuran ketone at 25 ° C the

solution undergo transformation to their

respective xanthenedione for 1h. In Figure

5 show the 1 H NMR spectra of a pure

tetraketone, but are displayed other signs

indicating that it is crude, which is at odds

with the melting point and mass spectrum

were performed compound. This sample

was left for 1h in NMR and after this time,

another was obtained spectrum is shown in

Figure 6. This new spectrum associated

with xanthenedione, ie, this proves that the

compound undergoes transformation and is

obtained from their respective pure

xanthenedione.

FIG 5. 1H RMN spectra of tetraketones on CDCl3

This result indicates that some triketones

can undergo transformation of their

respective xanthenediones in the body

because body temperature is above 36 °C

(16 °C higher than the temperature detected

by NMR).

FIG 6. 1H RMN spectra of one compound

transformed to xanthenedione in 1 h.

For this reason, it was important to

determine the function of tetrahydrofuran

ketones and their xanthenediones as

tyrosinase inhibitors, in particular to find

out if all of these compounds are effective

for the treatment of skin cancer, or if the

xanthenediones would provide other results,


72

including activation tyrosinase, a process

which can lead to increase cancer problems.

Therefore, in this study we decided to study

the effect of tetraketones and

xanthenediones on their activity in the

enzyme tyrosinase by UV-visible (Shin et

al, 1998). The results are shown in Table 1.

Table 1. Inhibition test and activation of the

enzyme tyrosinase using tetrahydrofuran ketones

and xanthenediones and L-tyrosine as substrate

All compounds were tested as inhibitors or

activators of the enzyme tyrosinase using

L-tyrosine or L-dopa as substrates by UV-

visible spectroscopy. These results from

Table 1 indicate that the respective

tetraketones are low potential inhibitors,

while certain of their xanthenediones are

strong activators of the enzyme tyrosinase.

The results indicate that using L-tyrosine as

substrate, confirms that tetraketones are

weak inhibitors of tyrosinase, while

xanthenediones with H and OCH 3 group in

the para position, increased enzyme

activity, especially no substituent group that

increases by more 170%. The results with

L-DOPA as a substrate also provided with

activation and inhibition of the enzyme.

NMR tests of relaxation time (T1 and T2),

diffusion coefficients (DOSY) and

saturation transfer difference (STD)

indicate that tetraketones interact with the

active site of this enzyme competing with

the substrates. However, the interaction of

xanthenediones is different, leading to the

activation of the enzyme.

Synthesis of furo [2,3-d] pyrimidine The first step consists in a Knoevenagel

condensation between an aromatic aldehyde

and barbituric acid for the preparation of

benzylidene barbiturate. In the next step,

the benzylidene barbiturate reacted with

isonitrile to form the furo [2,3-d]

pyrimidine, as shown in Figure 7.

FIG 7. Synthesis of furo[2,3-d]pyrimidine

All intermediates and final compounds

were characterized by melting point, IR and

NMR. The compounds of the first stage

were obtained in excellent yields (85-90%).

The furo [2,3-d] pyrimidines are

synthesized novel. These furo [2,3-d]

pyrimidines are tested as antibacterial and

antifungal.

Synthesis of compounds condensed with

the amino-benzaldehyde This part of the work were carried

condensation reactions of the amino-

benzaldehyde with activated methylenes

compounds. In this case it was used to

dimedone, barbituric acid, and Meldrum's

acid as shown in Figure 8.

FIG 8. Condensation reaction of the amino-

benzaldehyde with dimedone, barbituric acid, and

Meldrum acid

All compounds were characterized by

melting point, IR and NMR. The

synthesized compounds are all unpublished.

The yields of the compounds condensed

with barbituric acid, dimedone, and

Meldrum acid were obtained in good yields

(78, 82 and 70% respectively). All

compounds are tested as antibacterial and

antifungal.

These synthesized compounds possess a

similarity with the structure of tacrine

(Figure 9). Tacrine has been widely used as

a reversible inhibitor of

acetylcholinesterase. It was the first drug to

treat Alzheimer's disease. However, due to

its side effects, this drug has not been more

widely used. These condensed compounds


73

will be further studied for Alzheimer's

disease by our research group.

FIG 9. Tacrine structure

With the condensed compound of dimedone

it was accomplished the synthesis of a

guanylhydrazone through a reaction with

aminoguanidine hydrochloride using

butanol as a solvent at reflux (Figure 10).

FIG 10. Synthesis of guanylhydrazone derivate

from the compound condensed with dimedone

The compound was characterized by

melting point, IR and NMR. This

compound was obtained in 78% yield,

which is novel compound, it has not been

reported in the literature. Like other

condensed compounds, this will also tested

as antibacterial, antifungal and will also

made studies for Alzheimer's disease.

The student's last doctoral period missing

some biological activity testing and mass

spectra to finish their work. With the results

of synthesis and studies by NMR and

molecular modeling of tetraketones an

article was published in the Journal

Brazilian Chemical Society (JBCS). It is

being finalized an article on the enzyme

tyrosinase activation test and another article

on the synthesis of guanylhydrazones, and

these unpublished compounds.

5-SYNTHESIS,

CHARACTERIZATION AND

EVALUATION OF POTENTIAL

DRUGS FOR TREATMENT OF

BACTERIAL INFECTIONS

Antibiotics Antibiotics are considered a major

milestone of modern therapeutic medicine.

They have contributed to the increasing

success of medical treatments related to

bacterial infections and other procedures

such as surgery, transplantation and

chemotherapy. Moreover, in low-income

places that sanitation is scarce, antibiotics

have an important role to reduce the

morbidity and mortality caused by

infections (Rossolini et al., 2014).

Over the past 60 years, thousands of

antibiotics have been produced and

distributed worldwide, both as a medicine

as well as in most hygiene products,

cleaning products and others. In 2010 there

were 258 million dispensed oral antibiotics

(833 prescriptions per 1000 patients), and

50% are prescribed unnecessarily (Smith et

al., 2015).

The reduction of the spread of bacterial

infections through the correct use of

antibiotics and the development of new

drugs is an emergency measure and overall

responsibility (Cars et al., 2011).

Bacteria Escherichia coli bacteria is an anaerobic,

gram-negative, common gastrointestinal

system in humans and other animals, is

important for plants as a barrier against

colonization by pathogens. The E. coli

when it is out of their habitat cause serious

complications, such as their class

uropathogenic causing urinary tract

infection. It is opportunistic, can survive

and multiply within the cells and urinary

tract tissues becoming resistant to long

periods (Sousa 2006). These bacteria are

resistant to several types of β-lactam

antibiotics such as the third generation

cephalosporin (Schmidt et al., 2015).

Staphylococcus aureus is a spherical

bacterium, gram-positive cocci, in healthy

people is found on skin and nasal passages.

It is simple causing infections such as

pimples, cellulites and boils, but can also

cause serious infections among them

pneumonia, meningitis, sepsis and other

(Santos et al., 2007). This bacterium is

resistant to a range of antibiotics such as

penicillin, methicillin and 2002 was also

reported strains resistant to vancomycin

(Tortora, et al., 2012).

Streptococcus pneumoniae is a gram-

positive bacteria, facultative anaerobic, and

have a composite polysaccharide capsule

covering its cell wall, which confers

virulence for some serotypes of this

bacterium. S. pneumoniae is present in the

bacterial flora of the oropharynx and

nasopharynx of children and adults, and is

transmitted through splutter. Some strains

have showed resistance to β-lactam

antibiotics, macrolides and


74

fluoroquinolones (Nuermberger and Bishai,

2004).

Pseudomonas aeruginosa is a gram-

negative, aerobic, opportunistic and very

versatile. It is found in soil, water, plants

and well known to cause serious hospital

infections. This microorganism can cause

pneumonia in patients with cystic fibrosis,

bacteremia in immunocompromised and

nosocomial infections. Because it is a

versatile bacterium is resistant to many

classes of antibiotics available on the

market (Falkinham et al., 2015).

Bacterial resistance The first widely distributed penicillin

antibiotic was around 1940 and has been

documented after isolation of resistant

bacteria. From this framework until 1960

they were discovered 20 new classes of

antibiotics and was also seen the emergence

of many resistant strains. In the early 60s,

the research and development of new

antibiotics by the pharmacy industry

decreases and since 1962 only two new

classes were introduced. By contrast, there

was an increase in the use and distribution

of antibiotics (Smith et al., 2015).

During the last decade there has been a

great improvement in the control of

infections and antibiotics, but it is still a

worrying rate. These drugs are of great

importance in many surgical procedures,

chemotherapy and other diseases, and

depends entirely on its efficacy against the

micro-organism. However, with the

worldwide increase of antibiotic resistance,

the vast majority of pharmaceutical

companies closed its research and

development in the area. Today only some

of the largest companies remain the

antibacterial field. With that in recent

decades, we can see rare antibiotic

discoveries resulting in few newly approved

systemic medications (Harbarth et al.,

2015).

A major challenge in this area is the

economic investment, compared to other

areas. The pharmaceutical industry is facing

an increasingly significant number of low

cost off-patent antibiotics, as well as a

larger bureaucracy in hospitals and

limitations in the price of new drugs leaving

large disinterested industries in this area

(Harbarth et al., 2015).

Antibiotic resistance is a threat to treat

bacterial infections in all health care levels

with a local magnitude, national and global

(Grudmann et al., 2011). So it is extremely

important to search for new drugs.

Guanylhydrazones The guanylhydrazones are widely used due

to extensive therapeutic activity. It has been

reported on the biological activity literature

for Trypanosoma cruzi (Borges et al.,

2004), antitumor (Andreani et al., 2000),

anti-malarial (Silver and aviators, 1969)

and antimicrobial (Walzer et al. 1994 ;

Mitchell et al, 1998;. Gadad et al, 2000)..

The guanylhydrazone has an amidine group

(guanyl) connected to the hydrazone group

(Mitchell et al., 1998). The reaction of

compounds of interest is the chemo

selective aminoguanidine condensation

with aldehydes and / or ketones with

catalytic amounts of acid, in an alcoholic

medium under reflux. The guanylhydrazone

designation is appended after the name of

the aldehyde and / or ketone condensate

(Brito, 2014). This presents a nitrogen

group responsible for the synthesis of

different heterocycles (Gyordeak et al.

2004).

Objectives Synthesize, characterize new synthetic

substances with guanylhydrazone group

and assess possible biological activity.

1- Synthesis of new synthetic substances

from the condensation of 4-

aminobenzophenone with an aldehyde and

then the reaction with aminoguanidine.

2- Characterize the compounds formed by

melting point, nuclear magnetic resonance

of hydrogen, carbon nuclear magnetic

resonance and infrared. 3- Possible to

assess antibacterial activity against gram-

negative and gram-positive.

Methodology Step 1: The first step is to synthesize the

starting material for this will be conducted

condensation of 4-aminobenzophenone

with different aldehydes and

etoximetilenomalononitrila. This reaction

occurs in reflux with suitable solvent.

Step 2: The starting reactant is condensed

with N2H4 in acid solvent and determined

in advance. 2nd product: The reagent is

condensed with aminoguanidine with

catalytic amount of acid and a suitable

solvent to form the guanylhydrazone. 3rd

product: The starting reactant is condensed

with a nitrogen molecule containing a

carbonyl or sulfur in its composition.


75

Step 3: The obtained molecules are

characterized by melting point, nuclear

magnetic resonance of proton (1H-NMR),

nuclear magnetic resonance of carbon (13C

NMR) and infrared (IR) throughout the

period as the product of the synthesis is

made its characterization.

Step-4: Will be conducted in vitro tests

with the synthesized substances through

collaboration with other laboratory in the

FIOCRUZ.

Synthesis 1 From the 4-aminobenzophenone, it is

intended to synthesize potential

antibacterial agents by condensation with

various aldehydes. It is expected that these

compounds have biological activity against

strains of S. aureus, P. aeruginosa, E. coli

and S. pneumoniae (Figure 1).

FIG 1- Synthesis 1

Synthesis 2 The first will be held from 4-

aminobenzophenone, to form the compound

2 - ((4-Benzoylphenylamino) methylene)

malononitrila by a Michael condensation

with etoximetilenomalononitrilla reagent.

The remaining steps are the same as the

previous route.

FIG 2: Syntheis 2

Preliminary Results In a 50ml flask was added equimolar

concentrations of reactants and 4-

aminobenzophenone dinitrobenzaldeído

solubilized in 2,4-dioxane. It was added to

reflux at 140 ° C for 48h. There was the

formation of only one product. The solution

dried on the vacuum pump and the

precipitate recrystallized from ethanol. 1

The product was characterized by H1

NMR, C13 and infrared.

FIG 2- Product 1

FIG 3- 1H NMR spectrum of product 1

FIG 4- 13C NMR spectrum of product 1

FIG 5- IV spectrum of product 1

In a 50ml flask was added equimolar

amount of the reactants and 4-

aminobenzophenone

etoximetilenomalononitrila in ethanol. The

reaction was refluxed for 12 hours. After

cooling the solution, there was the

formation of precipitation. The solution was

filtered and the precipitate washed with

cold distilled water. 2 The product was

characterized by H NMR, C and infrared.


76



FIG 8- IV spectrum of product 2

Other prepared compounds were by

reaction of 2-hydroxybenzilidene

benzaldehyde with CH2(CN)2, as shown on

Figure 9

FIG 9- Synthesis of new agents for treatment of

bacterial infections

These compounds will be transformed to

other products, being one example shown

on Figure 10.

FIG 10- New expected compound

6- SYNTHESIS OF BENZENE

SULFONAMIDES REPLACED AS

POTENTIAL AGENTS FOR

REACTIVATION OF

ACETYLCHOLINESTERASE

INHIBITED BY NEUROTOXIC

ORGANOPHOSPHORUS

COMPOUNDS.

Summary of the initial project. Similarly to what happened in the world, in

Brazil there is a complex dispute between

humans, provided producers with own

consumption intention, and other species

for food. The research and development of

pesticides have the ultimate goal of

marketing of chemical, biological,

microbiological, semiochemicals,

hormones, growth regulators and enzymes

that have in common the property of acting

on other living beings whose presence in

the environment is a higher correlation to a

measurable economic loss.

These products are subject to an intense

state regulation in the research and

development stages, manufacturing,

registration (GARCIA-GARCIA; Bussacos;

FISCHER, 2005) and during its marketing

phase in rural and urban areas (Oliveira and

GOMES, 1990) in domestic and

international markets, in view of the role of

these products in relation to damage to

human health by contaminating the finished

product. There is also the issue of

anthropogenic changes in the environment

by changing the biota and there are

demands of society with regard to reducing

the environmental impact and encouraging

sustainable production.

The pesticides are selected based on an

intricate web of factors running through the

specificity of use depending on the culture


77

in question, part of a complex picture where

marketing and logistical issues have

importance (FRENKEL; Silveira, 1996).

The international trade of organophosphate

pesticides is the exchange of these products

across international borders or territories.

According to Brazil (2014), between 2009-

2012, the ten Brazilian states with the

highest commercialization of pesticides and

related products were: São Paulo, Minas

Gerais, Paraná, Santa Catarina, Rio Grande

do Sul, Goiás, Mato Grosso, Mato Grosso

do Sul, Bahia and Maranhão.

In Brazil, the registration of crop protection

is lifelong, contrary to what is allowed by

the laws of several other countries. In this

sense, UNISINOS (2015, p. 1):

"In Brazil, oddly enough, the re-

evaluation system by expiration of the

registration deadline has been banned.

Previously, under the rules of the Law

98.816 / 90, which was the first to

regulate Law 7802, the expiry date of a

pesticide registration was five years.

Elapsed this period, the industry should

request the renewal thereof, or spend

another licensing process which could be

required something more in favor of

environmental health. However, already

in 1993, Decree 991 eliminated this

requirement, which is still missing in the

current Decree 4,074 / 2002. Now, in

Brazil, to reassess some substance in

order to cancel your registration, it must

be that requested by any authority

referred to in the list of Article 5 of Law

7.802. In other words, the burden is

reversed for society to mobilize against

that substance should undergo constant

review. "

Perhaps the ramifications of this regulatory

landscape caused impact on research and

development activity carried out by

companies in this segment, which can be

classified as companies with proprietary

products and companies that focus on

manufacturing of generic agrochemicals

(PELAEZ; EARTH; SILVA, 2010).

Chemical pesticides can be studied apart

from other types, because its use is

associated with the specific chemical

structure of the active ingredient and its

formulation. In Brazil, official data updated

every six months by the Brazilian Institute

of Environment and Renewable Natural

Resources - IBAMA, link the set consists of

eight pesticides registered under several

different brands with the active ingredients

acephate (Cefanol®, Orthene®), ethephon

(Ethrel ®), chlorpyrifos (Dursban®,

Lorsban®), dichlorvos (DDVP®, Nuvan®,

Vapona®), dimethoate (Dimexion®,

Perfektion®), glyphosate (Round Up®),

malathion (Carbofós®, Malatol®,

Malaton®) and parathion (Folidol®) to be

responsible for 30% of the total tonnes of

chemical pesticides in 2014 (BRAZIL,

2014).

The pesticides from the group of

organophosphates are characterized by the

ability to inhibit irreversibly the

acetylcholinesterase enzyme, produced by

mammals, birds, insects, sea creatures and

man, is vital to the functioning of the

nervous system. Inhibition of this enzyme

causes devastating and naturally bodies

have different susceptibility profiles,

however, among the organophosphorus

compounds, neurotoxic agents show high

toxicity to mammals as well and obviously

for man, with military use of substances as

Brazil (1987) and Delfino, Ribeiro and

Figueroa-Villar (2009).

Table 1 - Nerve agents and their characteristics

for military use, adapted from Brazil (1987)

The chemical structures related to

neurotoxic agents listed in Table 1 are

shown in Figure 2.


78

FIG 2 – Chemical structures of the main nerve

warfare agents

According to Almeida (2015), from a

toxicological point of view of

organophosphorus pesticides and nerve

agents are the most toxic compounds which

have the property of inhibiting the enzyme

acetylcholinesterase (AChE), which is

distributed in the brain, ganglia, autonomic

nervous system, and the motor end plates

and has the primary role of degrading the

neurotransmitter acetylcholine in the

synapses.

Structurally, the monomer of human

acetylcholinesterase is classified as a

protein alpha / beta by presenting twelve

beta-pleated sheets and fourteen alpha-

helices, a total of 537 amino acids as shown

in Figure 3 below.

FIG 3 – Representação tridimensional da

acetilcolinesterase (Código PDB: 4PQE)

The active site of human AChE is

composed of the anionic site and esterático

site. The anionic site, comprising the amino

acid tyrosine 70, aspartate 72, tyrosine-121,

tryptophan-279 and tyrosine-334 has the

paper interact with the quaternary nitrogen

positively charged acetylcholine molecule,

while the esterático site formed by the triad

catalytic serine-203, histidine-447 and

glutamate 334, the latter site located at the

bottom of a cavity of approximately 20 Å in

depth, with oxygen in the serine 203

residue is 4 Å above the bottom of the well,

as shown in Figure 4 (Soares, 2010).

FIG 4 – Representation of the active site of

acetylcholinesterase and esterase

This dissertation proposes the

benzenesulfonamides potential study

replaced the reactivation of

acetylcholinesterase inhibited by

organophosphate dichlorvos agents,

malathion and paraoxon in vitro tests by the

spectrophotometric method of Ellman or

enzyme kinetics test by nuclear magnetic

resonance, and techniques already used in

studies conducted by members of the

Medicinal Chemistry Group, under the

guidance of Prof. PhD José Daniel Figueroa

Villar.

Step analysis fulfilled the period covered

by this report; Was planned and carried out the synthesis

of 23 benzenesulfonamides different

replaced using methods described in the

scientific literature (HOLMES, LAWTON,

1983; Rehmann et al, 2015;. PEAR;

Leggio; LIGUORI, 2006), being

sequentially performed physicochemical

characterization spectroscopy NMR, gas

chromatography and mass

spectrophotometer analysis by infrared

spectroscopy. The samples are sent for

conducting tests in vitro to evaluate the

potential for reactivation of the inhibited

acetylcholinesterase organophosphorus

agents over this period.

These compounds are now being tested by

NMR and Ellman test as reactivators of

acetylcholinesterase inhibited by neurotoxic

organophosphorus compounds, and also for

inhibition of AChE, their toxicity and the

capacity to penetration on the brain barrier.


79

AL5 main publications in 2016:

1- Diego Arantes Teixeira Pires, Wagner Luiz Pereira, Róbson Ricardo Teixeira, José Daniel Figueroa-Villar, Claudia Jorge do

Nascimento. Nuclear Magnetic Resonance (NMR), Infrared (IR) and Mass Spectrometry (MS) study of keto-enol tautomerism of

isobenzofuran-1(3H)-one derivatives. Journal of Molecular Structure. 10.1016/j.molstruc.2016.02.015, 2016.

2- DE SOUZA, LUANA G. , RENNÓ, MAGDALENA N. , FIGUEROA-VILLAR, JOSE D. . Coumarins as cholinesterase inhibitors: A

review. Chemico-Biological Interactions (Print), Artigo Publicado - JCR v. 262, p. 1-30, n. 2016.

3- SALES, E. M. , FIGUEROA-VILLAR, J. DANIEL . RECENT STUDIES ABOUT SYNTHESIS AND BIOLOGICAL ACTIVITY

OF QUINOLONES AND DERIVATIVES: A REVIEW. World Journal of Pharmacy and Pharmaceutical Sciences, v. 5, p. 253-268,

n. 2016.

4- AMIM, RAQUEL S. , FIRMINO, GISELE S. S. , REGO, A. C. , NERY, ADRIANE L. , DA-SILVA, SILVIA A. G. , SOUZA,

MARCUS V. N. DE , PESSOA, C. , JACKSON, A. , FIGUEROA-VILLAR, JOSÉ DANIEL , LESSA, J. A. . et al. Cytotoxicity and

Leishmanicidal Activity of Isoniazid-Derived Hydrazones and 2-Pyrazineformamide Thiosemocarbazones. Journal of the Brazilian

Chemical Society (Impresso), Artigo Publicado - JCR v. 27, p. 769-777, n. 2016.

5- PETRONILHO, ELAINE DA CONCEIÇÃO , RENNÓ, MAGDALENA DO NASCIMENTO , CASTRO, NEWTON GONÇALVES ,

DA SILVA, FERNANDA MOTTA R. , PINTO, Angelo da Cunha , FIGUEROA-VILLAR, JOSÉ DANIEL . Design, synthesis, and

evaluation of guanylhydrazones as potential inhibitors or reactivators of acetylcholinesterase. Journal of Enzyme Inhibition and

Medicinal Chemistry (Online), Artigo Publicado - JCR v. 31, p. 1-10, n. 2016.

6- DEAZEREDO, S. O. F. , SALES, E. M. , FIGUEROA-VILLAR, J D . Synthesis, Three-Dimensional Structure, Conformation and

Correct Chemical Shift Assignment Determination of Pharmaceutical Molecules by NMR and Molecular Modeling. Journal of the

Brazilian Chemical Society (Impresso), Artigo Publicado - JCR v. 27, p. '-10, n. 2016.

7- CRUZ, J.S. , COSTA, G.L. , FIGUEROA-VILLAR, J.D. . History, Applications, Activity and Changes of Citrinin. Revista Virtual de

Química, v. 8, p. 650-664, n. 2016.

AL5 main publications in 2015: 1- Ferreira, M. S.; José D. Figueroa-Villar. Método Alternativo Para a Síntese e Mecanismo de 2-(1,3-Ditiano-2-ilideno)-acetonitrila.

Química Nova, 38, 233, 2015.

2- Ferreira, M. S.; Pires, D. A. T.; José D. Figueroa-Villar. Evaluation of Tetraketones and Xanthenediones as Tyrosinase Inhibitors or

Activators. World Journal of Pharmacy and Pharmaceutical Sciences, 4, 1705-1718, 2015.

3- Figueroa-VillaR, José Daniel. Gated Decoupling 13C NMR Application to Determine Conformation and Unambiguous Chemical Shift

of Arylidene Barbiturates. Applied Magnetic Resonance, 46, 607-621, 2015.

4- Guimarães, E F; Vieira, A A; Rego, E C P; Garrido, B C; Rodrigues, J M; Figueroa-Villar, J D. Quantitative nuclear

magnetic resonance for purity assessment of polycyclic aromatic hydrocarbons. Metrologia, 52, L15-L22, 2015.

5- Vieira, Andreia Aguiar; Marinho, Bruno Guimarães; de souza, Luana Gonçalves; Fernandes, Patricia Dias; Figueroa-Villar, José D.

Design, synthesis and in vivo evaluation of sodium 2-benzyl-chloromalonates as new central nervous system depressants.

MedChemComm, 8, 1427-1437, 2015.

6- Petronilho, E. C.; Figueroa-Villar, J. Daniel. Agents for Defense Against Chemical Warfare: Reactivators of Acetylcholinesterase

Inhibited with Neurotoxic Organophosphorus Compounds. Military Medicine Science Letters, 84, 115-127, 2015.

7- Petronilho, Elaine da Conceição; Rennó, Magdalena do Nascimento; Castro, Newton Gonçalves; da Silva, Fernanda Motta R.; Pinto,

Angelo da Cunha; Figueroa-Villar, José Daniel. Design, synthesis, and evaluation of guanylhydrazones as potential inhibitors or

reactivators of acetylcholinesterase. Journal of Enzyme Inhibition and Medicinal Chemistry, 30, 1-10, 2015.

8- Amim, Raquel S.; Firmino, Gisele S. S.; Rego, Ana C. P. D.; Nery, Adriane L.; Da-SilvA, Silvia A. G.; Souza, Marcus V. N. De;

Pessoa, Claudia; Resende, Jackson A. L. C.; Figueroa-Villar, José D.; Lessa, Josane A. Cytotoxicity and Leishmanicidal Activity of

Isoniazid-Derived Hydrazones and 2-Pyrazineformamide Thiosemicarbazones. Journal of the Brazilian Chemical Society, 26, 1-9,

2015.

9- Petronilho, E. C.; Figueroa-Villar JD . Agentes para defesa contra guerra química: Reativadores de acetilcolinesterase inibida por

organofosforados neurotóxicos. In: Ângelo da Cunha Pinto. (Org.). Agentes para defesa contra guerra química: Reativadores de

acetilcolinesterase inibida por organofosforados neurotóxicos. 1ed.Rio de Janeiro: E-papers, 2015, v. 6, p. 113-128.

AL5 main publications in 2014:

1- Guimarães, Evelyn de Freitas; Rego, E. C. P.; Cunha HCM; Rodrigues JMR; Figueroa-Villar, J. Daniel. Certified Reference Material

for Traceability in Environmental Analysis: PAHs in Toluene. Journal of the Brazilian Chemical Society, 25, 351-360, 2014.

2- Ferreira, Marcelle De S. ; Figueroa-Villar, JOSÉ D. . Conformational Analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-

cyclohexene-1-one) by NMR and Molecular Modeling. Journal of the Brazilian Chemical Society, 25, 824-836, 2014.

3- Petronilho, Elaine da C.; Figueroa-Villar, José Daniel. Agents for Defense Against Chemical Warfare: Reactivators of the Inhibited

Acetylcholinesterase with Organophosphorus Neurotoxic Compounds. Revista Virtual de Química, 6, 671-686, 2014.

4- Deazeredo, S. O. F.; Figueroa-Villar, José Daniel. Phenanthrene Derivatives for Synthesis and Applications in Medicinal Chemistry: A

Review. World Journal of Pharmacy and Pharmaceutical Sciences, 3, 1362-1379, 2014.

5- Ferreira, Marcelle S.; Figueroa-Villar, José D. Alternative Method for Synthesis and Mechanism of 2-(1,3-Dithian-2-ylidene)-

acetonitrile. Química Nova, 38, 233-236, 2014.

AL5 main publications in 2013: 1- Figueroa-Villar, J. Daniel; Vieira, Andreia A. Nuclear magnetic resonance and molecular modeling study of exocyclic carbon carbon

double bond polarization in benzylidene barbiturates. Journal of Molecular Structure, 1034, 310-317, 2013.

2- Figueroa-Villar JD. Ética na Avaliação dos Cientistas. ComCiência, 147, 4-7, 2013.

3- Da Cunha Xavier Soares, Sibelle Feitosa; Vieira, Andréia Aguiar; Delfino, Reinaldo Teixeira; Figueroa-Villar, José Daniel. NMR

determination of Electrophorus electricus acetylcholinesterase inhibition and reactivation by neutral oximes. Bioorganic & Medicinal

Chemistry, 21, 5923-5930, 2013.

4- Gonçalves, Karla M.S.; Garcia, Danielle R; Ramalho, Teodorico Castro; Figueroa-Villar, José DanieL;

Freitas, Matheus Puggina de. Conformational Analysis of 1-Chloro- and 1-Bromo-2-Propanol. The Journal of

Physical Chemistry A, 117, 10980-10984, 2013.

5- Guimaraes, E. D. F.; Rodrigues, J. M.; Cruz, M. H. C. D. L.; Sartori, A. V.; De Souza, V.; Figueroa-Villar, J. D. Determination of

PAHs: A Practical Example of Validation and Uncertainty Assessment. Journal of Chromatographic Science, 51, 845-855, 2013.

6- Fioravante, A. L.; Guimarães, Evelyn de Freitas; Gonzaga, F. B.; Ribeiro, C. M.; Sobral, S. P.; Lopes, J. C.; Fraga, I. C. S.; Augusto,

C. R.; Elias, E. C. S.; Ribeiro, C. C.; Teixeira, D. C. G. S.; Rego, E. C. P.; Oliveira, L. M.; Santana, E. B.; Neves, L. A.; Almeida, R.

R. R.; Figueroa-Villar J. Daniel; Sena, R. C.; Dominguez, M. A.; Rodrigues JMR; Cunha, V. S. Developments of Environmental

Certified Reference Material from the Brazilian Metrology Institute to Support National Traceability. International Journal of

Measurement Technologies and Instrumentation Engineering, 3, 1-17, 2013.


80

LA 06 - Associate Laboratory of Proteins and Proteomic

Heterologous Expression

Coodinator: Hernán Terenzi – Departamento de Bioquímica/UFSC


Angela Menegatti; Hugo Braga

- Doctoral students:Nathalia Castilho – UFSC,

Philipe Gabriel – UFSC,

Ruth Fernandes – UFSC,

Vanessa Almeida - UFSC,

Vania Mareze- UFSC.


Ana Caroline Arruda de Souza- UFSC


Henrique Lückmann; Gabriel Tafarel

From 2013 to 2016 our group was

involved mainly in two subjects:

Biomimetic models of phosphatases and

covalent modification, and inhibition of

tyrosine phosphatases from pathogenic

microorganisms.

Serine/threonine protein phosphatases

have been described in many pathogenic

bacteria as essential enzymes involved in

phosphorylation-dependent signal

transduction pathways and frequently

associated with the virulence of these

organisms. An inspection of Mycoplasma

synoviae genome revealed the presence of

a gene (prpC) encoding a putative protein

phosphatase of the protein phosphatase 2C

(PP2C) subfamily. Here, we report a

complete biochemical characterization

of M. synoviae phosphatase (PrpC) and the

particular role of metal ions in the

structure–function relationship of this

enzyme. PrpC amino acid sequence

analysis revealed that all the residues

involved in the dinuclear metal center and

the putative third metal ion-coordinating

residues, conserved in PP2C phosphatases,

are present in PrpC. PrpC is a monomeric

protein able to dephosphorylate phospho-

substrates with Mn2+ ions’ dependence.

Thermal stability analysis demonstrated

the enzyme stability at mild temperatures

and the influence of Mn2+ ions in this

property. Mass spectrometry analysis

suggested that three metal ions bind to

PrpC, two of which with an apparent high-

affinity constant. Mutational analysis of

the putative third metal-coordinating

residues, Asp122 and Arg164, revealed

that these variants exhibited a weaker

binding of manganese ions, and that both

mutations affected PrpC phosphatase

activity. According to these results, PrpC

is a metal-dependent protein phosphatase

member with an improved stability in the

holo form and with Asp122, possibly

implicated in the third metal-binding site,

essential to catalytic activity (Figure 1).


81

Figure 1:Three-dimensional structural model of PrpC built using SaSTP from S. agalactiae as template.

A) The homology model of PrpC built with SWISS-MODEL using monomer B (PDB code 2PK0B,

magenta) and monomer C (PDB code 2PK0C, green) from SaSTP as template are superimposed using

PyMOL software. The models comparison showed two main differences: the flap subdomain

conformation and an additional α-helix indicated by an arrow. Overlay analysis using the DALI [2] and

SSM (Secondary Structure Matching) server [3] revealed a rootmean-square deviation (RMSD) of 1.3 Å

and 0.93 Å, respectively, between the two models. B) Superposition of the proposed metal-binding site of

the two PrpC homology models (from model built using 2PK0B, magenta, and from model built using

2PK0C, green, as template). Sticks show the residues conserved that coordinate the M1, M2 (PrpC

Asp19, Asp36, Gly37, Asp199 and Asp237) and the putative M3 (PrpC Asp122, Asp199 and Arg164) site.

C) The structures of PrpC (red, built using 2PK0C as template) and SaSTP from S. agalactiae (PDB code

2PK0C, cyan) are superimposed. The three metal ions in the active site are shown as orange spheres.

Overlay analysis using the DALI [2] and SSM server [3] revealed a RMSD of 0.8 Å and 1.08 Å,

respectively, between the two structures. D) Superposition of the proposed metal-binding pocket of PrpC

(red, built using 2PK0C as template) and SaSTP (PDB code 2PK0C, cyan). Sticks show the conserved

residues that coordinate the M1, M2 (PrpC Asp19, Asp36, Gly37, Asp199 and Asp237) and the putative

M3 (PrpC Asp122, Asp199 and Arg164) site. PyMOL [4] was used to represent the homology model of

the PrpC

Furthermore, YopH tyrosine phosphatase,

a virulence factor produced by pathogenic

species of Yersinia, plays a relevant role in

three pathogenic species of Yersinia. Due

to its importance in the prevention of the

inflammatory response of the host, this

enzyme has become a valid target for the

identification and development of new

inhibitors. In 2013, we assayed, an in-

house library of 283 synthetic compounds

against recombinant YopH from Yersinia

enterocolitica. From these, four chalcone

derivatives and one sulfonamide were

identified for the first time as competitive

inhibitors of YopH with binding affinity in

the low micromolar range. Molecular

modeling investigations indicated that the

new inhibitors showed similar binding

modes, establishing polar and hydrophobic

contacts with key residues of the YopH

binding site.

Also, YopH is an attractive drug target. In

2015, we assayed three

oxidovanadium(IV) complexes against

recombinant YopH and showed strong

inhibition of the enzyme in the nanomolar

range. Molecular modeling indicated that

their binding is reinforced by H-bond,

cation−π, and π–π interactions conferring

specificity toward YopH. These

complexes are thus interesting lead

molecules for phosphatase inhibitor drug


82

discovery (Figure 2).

Figure 2. Predicted binding conformation of oxidovanadium complexes 1–3 to YopH. (A) Docking-based

binding mode of 1, the most active inhibitor of the series; (B) docking-based binding mode of 2; (C)

docking-based binding mode of 3. Ligands are shown as cyan sticks, vanadium as gray sphere. The

crystallographic structure of YopH (PDB 3F9B) is shown as green cartoon and lines. Residues involved in

binding to 1–3 are shown as orange sticks and are labeled. Ligand nonpolar H atoms were omitted. H-bond

interactions are shown as black dashed lines.

Likewise, Falcipain-2 (FP-2) is a key

cysteine protease from the malaria

parasite Plasmodium falciparum. Many

previous studies have identified FP-2

inhibitors; however, none has yet met the

criteria for an antimalarial drug candidate.

We assayed an in-house library of non-

peptidic organic compounds, including

(E)-chalcones, (E)-N’-benzylidene-

benzohydrazides and alkyl-esters of gallic

acid, and assessed the activity toward FP-2

and their mechanisms of inhibition. The

(E)-chalcones 48, 54 and 66 showed the

lowest IC50values (8.5 ± 0.8 µM,

9.5 ± 0.2 µM and 4.9 ± 1.3 µM,

respectively). The best inhibitor

(compound 66) demonstrated non-

competitive inhibition, and using mass

spectrometry and fluorescence

spectroscopy assays, we suggest a

potential allosteric site for the interaction

of this compound, located between the

catalytic site and the hemoglobin binding

arm in FP-2. We combined structural

biology tools and mass spectrometry to

characterize the inhibition mechanisms of

novel compounds targeting FP-2.

S-nitrosylation is associated with signal

transduction and microbicidal activity of

nitric oxide (NO). We have recently

described the S-nitrosylation

of Mycobacterium tuberculosis protein

tyrosine phosphatase A, PtpA, an enzyme

that plays an important role in

mycobacteria survival inside

macrophages. This post-translational

modification decreases the activity of the

enzyme upon modification of a single Cys

residue, C53. We investigated of the effect

of S-nitrosylation in PtpA kinetic

parameters, thermal stability and structure.

It was observed that the KM of

nitrosylated PtpA was similar to its

unmodified form, but the Vmax was

significantly reduced. In contrast,

treatment of PtpA C53A with GSNO, did

not alter either KM or Vmax. These results

confirmed that PtpA S-nitrosylation occurs

specifically in the non-catalytic C53 and

that this modification does not affect

substrate affinity. Using circular dichroism

(CD) and nuclear magnetic resonance

(NMR) spectroscopy techniques it was

shown that PtpA S-nitrosylation decreased

protein thermal stability and promoted a

local effect in the surroundings of the C53

residue, which interfered in both protein

stability and function.

we also reported the synthesis,

characterization, and hydrolase-like

activity of a new mononuclear

LaIII complex 1 containing a LaIII-bound

phenolate with a carbonyl functional

group. When linked to 3-aminopropyl-


83

functionalized silica (APS), the

mononuclear complex undergoes

disproportionation to form a dinuclear

species APS-

[(OH)LaIII(μ−OH)LaIII(OH2)], whose

catalytic efficiency is increased when

compared to the homogeneous reaction,

and the anchored catalyst APS-1 can be

recovered and reused for subsequent

hydrolysis reactions.


1. AURAS, BRUNA L. ; OLIVEIRA, VANESSA A. ; TERENZI, HERNAN ; NEVES, ADEMIR ; IGLESIAS, BERNARDO

ALMEIDA . Meso-mono-[4-(1,4,7-triazacyclononanyl)]-tri(phenyl)]porphyrin and respective zinc(II)-complex: complete

characterization and biomolecules binding abilities. Photochemical & Photobiological Sciences (Print) , v. 12, p. 2, 2016.

http://dx.doi.org/10.1039/c6pp00016a

2. BERTOLDO, JEAN BORGES ; TERENZI, HERNAN . Oxidation and Tyrosine Nitration Induce Structural Changes and Inhibits

Plasmodium falciparum Falcipain-2 Activity In Vitro. Protein and Peptide Letters , v. 23, p. 562-572, 2016.

http://dx.doi.org/10.2174/0929866523666160411144635

3. BORTOLOTTO, TIAGO ; SILVA-CALDEIRA, PRISCILA PEREIRA ; PICH, CLAUS TRÖGER ; PEREIRA-MAIA, ELENE

CRISTINA ; TERENZI, HERNAN . Tunable DNA cleavage activity promoted by copper(II) ternary complexes with N-donor

heterocyclic ligands. Chemical Communications (London. 1996. Print) , v. accept, p. 1-4, 2016.

http://dx.doi.org/10.1039/C6CC03142K

4. GUERRA, W. ; SILVA-CALDEIRA P ; TERENZI, HERNAN ; MAIA, ELENE C PEREIRA . Impact of metal coordination on the

antibiotic and non-antibiotic activities of tetracycline-based drugs. Coordination Chemistry Reviews (Print) , p. 1, 2016.

http://dx.doi.org/10.1016/j.ccr.2016.04.009

5. MASCARELLO,A ; CHIARADIA, L. D. ; MORI, MATTIA ; TERENZI, H ; BOTTA, B . Mycobacterium tuberculosis-Secreted

Tyrosine Phosphatases as Targets Against Tuberculosis: Exploring Natural Sources in Searching for New Drugs2. Current

Pharmaceutical Design (Print), v. 12, p. 12, 2016. http://dx.doi.org/10.2174/1381612822666160112130539

6. MENEGATTI, ANGELA ; TERENZI, HERNAN . Phosphorylation Signaling in Mycobacterium tuberculosis: an overview. Forum on

Immunopathological Diseases and Therapeutics, v. 1, p. 1, 2016. http://dx.doi.org/10.1615/ForumImmunDisTher.2016016732

7. OLIVEIRA, VANESSA A. ; IGLESIAS, BERNARDO ALMEIDA ; AURAS, BRUNA L. ; NEVES, ADEMIR ; TERENZI,

HERNAN . Photoactive meso-tetra(4-pyridyl)porphyrin-tetrakis-[chloro(2,2´bipyridine)platinum(II) derivatives recognize and cleave

DNA upon irradiation. Dalton Transactions (2003. Print) , v. 1, p. 1, 2016. http://dx.doi.org/10.1039/C6DT04634G


1. CAMARGO, T. ; MAIA, F. ; CHAVES, C. ; SOUZA, B. ; BORTOLUZZI, ADAILTON J. ; CASTILHO, N. ; BORTOLOTTO, T. ;

TERENZI, H ; CASTELLANO, EDUARDO ; HAASE, WOLFGANG ; TOMKOWICZ, Z. ; PERALTA, ROSELY A. ; NEVES, ADEMIR .

Synthesis, characterization, hydrolase and catecholase activity of a dinuclear iron(III) complex: Catalytic promiscuity. Journal of Inorganic

Biochemistry, v. 146, p. 77-88, 2015. 10.1016/j.jinorgbio.2015.02.017

2. LAMOTTE, O. ; BERTOLDO, J. ; BARD, A.B. ; TERENZI, H ; WENDEHENNE, D. . Protein S-nitrosylation: specificity and identification

strategies in plants. Frontiers in Chemistry, v. 2, p. 1, 2015. DOI: 10.3389/fchem.2014.00114

3. MARGENAT, MARIANA ; LABANDERA, ANNE-MARIE ; GIL, MAGDALENA ; CARRION, FEDERICO ; PURIFICAÇÃO,

MARCELA ; RAZZERA, GUILHERME ; PORTELA, MARÍA MAGDALENA ; OBAL, GONZALO ; TERENZI, HERNÁN ; PRITSCH,

OTTO ; DURÁN, ROSARIO ; FERREIRA, ANA MARÍA ; VILLARINO, ANDREA . New potential eukaryotic substrates of the

mycobacterial protein tyrosine phosphatase PtpA: hints of a bacterial modulation of macrophage bioenergetics state. Scientific Reports, v. 5,

p. 8819, 2015. DOI: 10.1038/srep08819

4. MARTINS, PRISCILA G.A. ; MORI, MATTIA ; CHIARADIA-DELATORRE, LOUISE DOMENEGHINI ; MENEGATTI, ANGELA

CAMILA ORBEM ; MASCARELLO, ALESSANDRA ; BOTTA, BRUNO ; BENITEZ, JULIO ; GAMBINO, DINORAH ; TERENZI,

HERNÁN . Exploring oxidovanadium(IV) complexes as YopH inhibitors: mechanism of action and modeling studies. ACS MED CHEM

LETT, v. 1, p. 150831155241006, 2015. DOI: 10.1021/acsmedchemlett.5b00267

5. TAVARES, CAROLINA PEREIRA ; TERENZI, HERNÁN . Biochemical analysis of the interaction between Arabidopsis thaliana

AtMYB30 transcription factor and its DNA specific target site. Journal of Plant Biochemistry and Biotechnology, v. 12, p. 12, 2015. DOI:

10.1007/s13562-015-0315-9


1. BERTOLDO, J. ; CHIARADIA, L. D. ; MASCARELLO,A ; NUNES, RICARDO JOSE ; ROSENTHAL, P. ; SALAS SARDUY, E. ;

TERENZI, H . Synthetic compounds from an in house library as inhibitors of falcipain-2 from Plasmodium falciparum. Journal of Enzyme

Inhibition and Medicinal Chemistry (Print), v. 0001, p. 1-9, 2014. DOI: 10.3109/14756366.2014.920839

2. MASSOUD, S. ; PERKINS, R. S. ; LOUKA, F. R. ; XU, W. ; LE ROUX, A. ; DUQTERCQ, Q. ; FISCHER, R. C. ; MAUTNER, F. A. ;

HANDA, M. ; HIRAOKA, Y. ; KREFT, G. L. ; BORTOLOTTO, T. ; TERENZI, H. . Efficient hydrolytic cleavage of plasmid DNA by

chloro-cobalt(ii) complexes based on sterically hindered pyridyl tripod tetraamine ligands: synthesis, crystal structure and DNA cleavage.

Dalton Transactions (2003. Print), v. 43, p. 10086, 2014. DOI: 10.1039/C4DT00615A

3. MENEGATTI, A. ; VERNAL, JAVIER ; TERENZI, H . The unique serine/threonine phosphatase from the minimal bacterium Mycoplasma

synoviae: biochemical characterization and metal dependence. JBIC. Journal of Biological Inorganic Chemistry (Print), p. 1, 2014. DOI:

10.1007/s00775-014-1209-3

4. MUXEL, A. ; NEVES, ADEMIR ; CAMARGO, MARYENE A. ; BORTOLUZZI, ADAILTON J. ; SZPOGANICZ, B ; CASTELLANO, E

; CASTILHO, N. ; BORTOLOTTO, TIAGO ; TERENZI, H . New La(III) Complex Immobilized on 3-Aminopropyl-Functionalized Silica as

an Efficient and Reusable Catalyst for Hydrolysis of Phosphate Ester Bonds. Inorganic Chemistry, v. 545, p. 140303155441001, 2014. DOI:

10.1021/ic402705r

5. TAVARES, CAROLINA P. ; VERNAL, JAVIER ; DELENA, R. ; LAMATTINA, L. ; CASSIA, R. O. ; TERENZI, H . S-nitrosylation

influences the structure and DNA binding activity of AtMYB30 transcription factor from Arabidopsis thaliana. Biochimica et Biophysica

Acta. Proteins and Proteomics, v. 11, p. 22, 2014. DOI:10.1016/j.bbapap.2014.02.015


1. DE ALMEIDA, VICENTE R. ; XAVIER, FERNANDO R. ; OSÓRIO, RENATA E. H. M. B. ; BESSA, L. M. ; SCHILLING, E. ;






















http://dx.doi.org/10.3389/fchem.2014.00114




























84

COSTA, T. G. ; BORTOLOTTO, TIAGO ; CAVALETT, ANGÉLICA ; CASTRO, F. A. ; VILHENA, F. ; ALVES, O. C. ;

TERENZI, H. ; ELEUTHERIO, E. C. A. ; PEREIRA, M. D. ; HAASE, WOLFGANG ; TOMKOWICZ, ZBIGNIEW ;

SZPOGANICZ, BRUNO ; BORTOLUZZI, ADAILTON J. ; NEVES, ADEMIR . In vitro and in vivo activity of a new unsymmetrical

dinuclear copper complex containing a derivative ligand of 1,4,7-triazacyclononane: catalytic promiscuity of [Cu2(L)Cl3]. Dalton

Transactions (2003. Print), v. 42, p. 7059, 2013. DOI: 10.1039/C3DT33046J

2. HORN JR, ADOLFO ; FERNANDES C ; PARRILHA G L ; SCHENK, GERHARD ; TERENZI, HERNA N ; PICH, CLAUS .

Highly efficient synthetic iron-dependent nucleases activate both intrinsic and extrinsic apoptotic death pathways in leukemia cancer

cells. Journal of Inorganic Biochemistry, v. 128, p. 38-47, 2013. DOI:. 10.1016/j.ejmech.2013.04.018

3. MARTINS, PRISCILA GRAZIELA ALVES ; MENEGATTI, A. ; CHIARADIA, L. D. ; GUIDO, RAFAEL V.C. ; ANDRICOPULO,

A. ; VERNAL, JAVIER ; YUNES, R. A. ; NUNES, RICARDO JOSE ; TERENZI, HERNAN . Synthetic chalcones and sulfonamides

as new classes of Yersinia enterocolitica YopH tyrosine phosphatase inhibitors. European Journal of Medicinal Chemistry, v. 64, p.

35-41, 2013. DOI:. 10.1016/j.ejmech.2013.04.018

4. MASCARELLO,A ; CHIARADIA, L. D. ; YUNES, ROSENDO AUGUSTO ; NUNES, RICARDO JOSE ; TERENZI, H. ; BOTTA,

B . Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (PtpB) Inhibitors from Natural Products. Plos One, v. 8,

p. e77081, 2013. DOI: 10.1371/journal.pone.0077081

5. MATIOLLO, CAMILA ; ECCO, GABRIELA ; MENEGATTI, A. ; RAZZERA, G. ; VERNAL, JAVIER ; TERENZI, H . S-

nitrosylation of Mycobacterium tuberculosis tyrosine phosphatase A (PtpA) induces its structural instability. Biochimica et Biophysica

Acta. Proteins and Proteomics, v. 1834, p. 191-196, 2013. DOI: 10.1016/j.bbapap.2012.10.007

6. SILVA, PRISCILA P. ; GUERRA, W. ; SILVEIRA, JOSIANE N. ; FERREIRA, ANA MARIA DA C. ; BORTOLOTTO, TIAGO ;

TERENZI, HERNAN ; BORTOLUZZI, ADAILTON J. ; NEVES, ADEMIR ; MAIA, ELENE C PEREIRA . Correlation between

DNA interactions and cytotoxic activity of four new ternary compounds of copper(II) with N-donor heterocyclic ligands. Journal of

Inorganic Biochemistry, v. 01, p. 01, 2013. DOI:. 10.1016/j.ejmech.2013.04.018

7. SOUZA, B. ; KREFT, G. L. ; BORTOLOTTO, T. ; TERENZI, HERNAN ; BORTOLUZZI, ADAILTON J ; CASTELLANO,

EDUARDO ; DOMINGOS, J.B. ; NEVES, ADEMIR . Second-Coordination-Sphere Effects Increase the Catalytic Efficiency of an

Extended Model for Fe III M II Purple Acid Phosphatases. Inorganic Chemistry, p. 130315150407001, 2013. DOI: 10.1021/ic400025j


85

LA 7- Associated Laboratory of Proteins Biochemistry

- Coodinator:

Carlos Henrique Inácio Ramos. UNICAMP


Ljubica Tasic. UNICAMP


Glaucia Melina Squizato Pinheiro

(UNICAMP),

Käthe Margareta Dahlström (UNICAMP),

Lucimara Lopes da Silva (UNICAMP),

Maria Luiza Caldas Nogueira

(UNICAMP),

Regina Célia Adão (UNICAMP)


Banny Silva Barbosa (UNICAMP),

Conrado de Campos Gonçalves

(UNICAMP),

Daniela Zacharias Cypriano (UNICAMP),

Danijela Stanisic (UNICAMP),

Izabella Venturini Cagliari (UNICAMP),

João Guilherme de Moraes Pontes

(UNICAMP),

Josielle Abrahão (UNICAMP),

Mayra Alejandra Mariño Bohórquez

(UNICAMP),

Natalia Galdi Quel (UNICAMP),

Tássia Brena Barroso Carneiro da Costa

(UNICAMP)


Caio Henrique Nasi de Barros

(UNICAMP),

Gabriela de Mello Gandelini

(UNICAMP),

Juliana Crotti Franco (UNICAMP),

Lilian Goulart Schultz (UNICAMP),

Stephanie Fernanda Fulaz (UNICAMP).


Antônio Jadson M. Brasil (UNICAMP),

Débora Bueno Toledo (UNICAMP),

Bruna Furlan (UNICAMP),

Giovanna Grilo (UNICAMP),

Leonardo Monteiro (UNICAMP),

Franciso dos Santos (UNICAMP),

Letícia Huan Bacellar Liu (UNICAMP),

Luiz Rodrigues (UNICAMP),

Paula Moretti (UNICAMP)

All cells, and consequently all

living organisms, depend on proteins.

These biomolecules are involved in almost

all physiological functions, including

catalysis, transport, signaling and

movement. The lifespan of each protein is

generally controlled, as the expression and

degradation of these biomolecules are well

regulated. Transcription factors and the

proteasome are established examples of

regulators of these processes.

Additionally, a protein’s conformation is

closely related to its function; thus, its

folding state is also a target of regulation.

Molecular chaperones and heat shock

proteins assist in proper protein folding

and prevent misfolding. A significant

portion of the proteome is assisted by this

class of proteins, which may be divided

into foldases (assistants of folding and

refolding), holdases (preventers of

unfolding and misfolding), and

disaggregases (involved in solubilizing

aggregates). This last function has become

of great interest recently, as aggregates

have been linked to cytotoxicity and

consequently to many diseases. The

chaperones from the Hsp70 and Hsp90

families are the best known examples of

foldases, while the chaperones from the

Hsp40 and smHsp (small Hsp) families are

the best known examples of holdases.

Hsp100 chaperones appear to be the

unique examples of disaggregases. To


86

learn more about molecular chaperones,

we took to clone and purify proteins

belonging to this Family from several

organims such as human, plants and yeast.

These proteins are characterized by

biphysical and biochemical tools to

undertand the relationship between

structure and funtion in chaperones. We

also investigate protein-protein and protein

ligand interactions. Bellow, we sumarize

the main findings of four investigations.

The human mitochondrial Hsp70,

also called mortalin, is of considerable

importance for mitochondria biogenesis

and the correct functioning of the cell

machinery. In the mitochondrial matrix,

mortalin acts in the importing and folding

process of nucleus-encoded proteins. The

in vivo deregulation of mortalin

expression and/or function has been

correlated with age-related diseases and

certain cancers due to its interaction with

the p53 protein. In spite of its critical

biological roles, structural and functional

studies on mortalin are limited by its

insoluble recombinant production. Our

study provides the first report of the

production of folded and soluble

recombinant mortalin when co-expressed

with the human Hsp70-escort protein 1,

but it is still likely prone to self-

association. The monomeric fraction of

mortalin presented a slightly elongated

shape and basal ATPase activity that is

higher than that of its cytoplasmic

counterpart Hsp70-1A, suggesting that it

was obtained in the functional state.

Through small angle X-ray scattering, we

assessed the low-resolution structural

model of monomeric mortalin that is

characterized by an elongated shape. This

model adequately accommodated high

resolution structures of Hsp70 domains

indicating its quality. We also observed

that mortalin interacts with adenosine

nucleotides with high affinity. Thermally

induced unfolding experiments indicated

that mortalin is formed by at least two

domains and that the transition is sensitive

to the presence of adenosine nucleotides

and that this process is dependent on the

presence of Mg2+ ions. Interestingly, the

thermal-induced unfolding assays of

mortalin suggested the presence of an

aggregation/association event, which was

not observed for human Hsp70-1A, and

this finding may explain its natural

tendency for in vivo aggregation. Our

study contributes to the structural

understanding of mortalin as well as to

contribute for its recombinant production

for antitumor compound screenings.

The p23 protein is a chaperone

widely involved in protein homeostasis,

well known as an Hsp90 co-chaperone

since it also controls the Hsp90 chaperone

cycle. Human p23 includes a β-sheet

domain, responsible for interacting with

Hsp90; and a charged C-terminal region

whose function is not clear, but seems to

be natively unfolded. p23 can undergo

caspase-dependent proteolytic cleavage to

form p19 (p231-142), which is involved in

apoptosis, while p23 has anti-apoptotic

activity. To better elucidate the function of

the human p23 C-terminal region, we

studied comparatively the full-length

human p23 and three C-terminal

truncation mutants: p23₁₋₁₁₇; p23₁₋₁₃₁ and p23₁₋₁₄₂. Our data indicate that p23

and p19 have distinct characteristics,

whereas the other two truncations behave

similarly, with some differences to p23

and p19. We found that part of the C-

terminal region can fold in an α-helix

conformation and slightly contributes to

p23 thermal-stability, suggesting that the

C-terminal interacts with the β-sheet

domain. As a whole, our results suggest

that the C-terminal region of p23 is critical

for its structure-function relationship. A

mechanism where the human p23 C-

terminal region behaves as an

activation/inhibition module for different

p23 activities is proposed.

Hsp90 is a molecular chaperone

essential for cell viability in eukaryotes

that is associated with the maturation of

proteins involved in important cell

functions and implicated in the

stabilization of the tumor phenotype of

various cancers, making this chaperone a

notably interesting therapeutic target.

Celastrol is a plant-derived pentacyclic

triterpenoid compound with potent

antioxidant, anti-inflammatory and

anticancer activities; however, celastrol's

action mode is still elusive. We


87

investigated the effect of celastrol on the

conformational and functional aspects of

Hsp90α. Interestingly, celastrol appeared

to target Hsp90α directly as the compound

induced the oligomerization of the

chaperone via the C-terminal domain as

demonstrated by experiments using a

deletion mutant. The nature of the

oligomers was investigated by biophysical

tools demonstrating that a two-fold excess

of celastrol induced the formation of a

decameric Hsp90α bound throughout the

C-terminal domain. When bound, celastrol

destabilized the C-terminal domain.

Surprisingly, standard chaperone

functional investigations demonstrated that

neither the in vitro chaperone activity of

protecting against aggregation nor the

ability to bind a TPR co-chaperone, which

binds to the C-terminus of Hsp90α, were

affected by celastrol. Celastrol interferes

with specific biological functions of

Hsp90α. Our results suggest a model in

which celastrol binds directly to the C-

terminal domain of Hsp90α causing

oligomerization. However, the ability to

protect against protein aggregation

(supported by our results) and to bind to

TPR co-chaperones are not affected by

celastrol. Therefore celastrol may act

primarily by inducing specific

oligomerization that affects some, but not

all, of the functions of Hsp90α. This study

was the first work to use multiple probes

to investigate the effect that celastrol has

on the stability and oligomerization of

Hsp90α and on the binding of this

chaperone to Tom70. This work provides a

novel mechanism by which celastrol binds

Hsp90α.

Also, Despite a wealth of studies

conducted on the relevance of

Tom70·Hsp90 complex formation, there is

a dearth of information regarding the exact

molecular mode of interaction. To help fill

this void, we have employed a combined

experimental strategy consisting of cross-

linking/mass spectrometry to investigate

binding of the C-terminal Hsp90 domain

to the cytosolic domain of Tom70. This

approach has identified a novel region of

contact between C-Hsp90 and Tom70, a

finding that is confirmed by probing the

corresponding peptides derived from

cross-linking experiments via isothermal

titration calorimetry and mitochondrial

import assays. The data generated in this

study are combined to input constraints for

a molecular model of the Hsp90/Tom70

interaction, which has been validated by

small angle x-ray scattering,

hydrogen/deuterium exchange, and mass

spectrometry. The resultant model

suggests that only one of the MEEVD

motifs within dimeric Hsp90 contacts

Tom70. Collectively, our findings provide

significant insight on the mechanisms by

which preproteins interact with Hsp90 and

are translocated via Tom70 to the

mitochondria (Figure 1).

Figure1: C-Hsp90/Tom70 model from cross-linking and SAXS data. A) C-Hsp90/Tom70 binding interface

characterized by XL. The C-Hsp90 and Tom70 binding interfaces appear in red, orange, green, and

magenta, and the MEEVD motif and its recognition site in yellow. B) regions in Tom70 impacted by the

presence of the MEEVD peptide are in red


88

Hsp70 cycles from an ATP-bound

state, in which the affinity for unfolded

polypeptides is low, to an ADP-bound

state, in which the affinity for unfolded

polypeptides is high, to assist with cell

proteostasis. Such cycling also depends on

co-chaperones because these proteins

control both the Hsp70 ATPase activity

and the delivery of unfolded polypeptide

chains. Although it is very important,

structural information on the entire protein

is still scarce. This work describes the first

cloning of a cDNA predicted to code for a

cytosolic Saccharum spp. (sugarcane)

Hsp70, named SsHsp70 here, the

purification of the recombinant protein and

the characterization of its structural

conformation in solution by chemical

cross-linking coupled to mass

spectrometry. The in vivo expression of

SsHsp70 in sugarcane extracts was

confirmed by Western blot. Recombinant

SsHsp70 was monomeric, both ADP and

ATP binding increased its stability and it

was efficient in cooperating with co-

chaperones: ATPase activity was

stimulated by Hsp40s, and it aided the

refolding of an unfolded polypeptide

delivered by a member of the small Hsp

family. The structural conformation results

favor a model in which nucleotide-free

SsHsp70 is highly dynamic and may

fluctuate among different conformations

that may resemble those in which

nucleotide is bound. Validation of a

sugarcane EST as a true mRNA that

encodes a cytosolic Hsp70 (SsHsp70) as

confirmed by in vivo expression and

characterization of the structure and

function of the recombinant protein.

SsHsp70 was monomeric, both ADP and

ATP binding increased its stability and

was efficient in interacting and

cooperating with co-chaperones to

enhance ATPase activity and refold

unfolded proteins. The conformation of

nucleotide-free SsHsp70 in solution was

much more dynamic than suggested by

crystal structures of other Hsp70s.

Hsp90s are involved in several

cellular processes, such as signaling,

proteostasis, epigenetics, differentiation

and stress defense. Although Hsp90s from

different organisms are highly similar,

they usually have small variations in

conformation and function. Thus, the

characterization of different Hsp90s is

important to gain insight into the structure-

function relationship that makes these

chaperones key regulators in protein

homeostasis. We characterize of a

cytosolic Hsp90 from sugarcane and its

comparison with Hsp90s from other

plants. Previous expressed sequence tag

(EST) studies in Saccharum spp.

(sugarcane) predicted the presence of an

mRNA coding for a cytosolic Hsp90. The

corresponding cDNA was cloned, and the

recombinant protein was purified and its

conformation and function characterized.

The structural conformation of Hsp90 was

assessed by chemical cross-linking and

hydrogen/deuterium exchange using mass

spectrometry and hydrodynamic assays,

which revealed regions accessible to

solvent and that Hsp90 is an elongated

dimer in solution. The in vivo expression

of Hsp90 in sugarcane leaves was

confirmed by western blot, and in vitro

functional characterization indicated that

sugarcane Hsp90 has strong chaperone

activity.


1. BALLOTTIN, DANIELA ; FULAZ, STEPHANIE ; SOUZA, MICHELE L. ; CORIO, PAOLA ; Rodrigues, Alexandre G. ; SOUZA,

ANA O. ; GASPARI, PRISCYLA M. ; GOMES, ALEXANDRE F. ; GOZZO, FÁBIO ; Tasic, Ljubica . Elucidating Protein

Involvement in the Stabilization of the Biogenic Silver Nanoparticles. Nanoscale Research Letters (Online), v. 11, p. 1-9, 2016.

http://dx.doi.org/10.1186/s11671-016-1538-y

2. BATISTA, FERNANDA A.H. ; SERAPHIM, THIAGO V. ; SANTOS, CLELTON A. ; GONZAGA, MARISVANDA R. ;

BARBOSA, LEANDRO R.S. ; RAMOS, CARLOS H.I. ; BORGES, JÚLIO C. . Low sequence identity but high structural and

functional conservation: The case of Hsp70/Hsp90 organizing protein (Hop/Sti1) of Leishmania braziliensis. Archives of

Biochemistry and Biophysics (Print), v. 600, p. 12-22, 2016. http://dx.doi.org/10.1016/j.abb.2016.04.008

3. DANTAS, LARISSA ELIZABETH C; RAMOS, CARLOS HENRIQUE I; BENICHOU, SERGE; SAAD, SARA TERESINHA

OLALLA (2016) Overexpression, purification and characterization of the C-terminal domain of human SIVA1, an apoptosis-

inducing factor. Prot Pep Letters 23, 43-50.


89

4. DURÁN, NELSON ; JUSTO, GISELLE Z. ; DURÁN, MARCELA ; BROCCHI, MARCELO ; CORDI, LIVIA ; Tasic, Ljubica ;

CASTRO, GUILLERMO R. ; NAKAZATO, GERSON . Advances in Chromobacterium violaceum and properties of violacein-Its

main secondary metabolite: A review. Biotechnology Advances, v. 34, p. 1030-1045, 2016.

http://dx.doi.org/10.1016/j.biotechadv.2016.06.003

5. GONCALVES, C. C. ; RAMOS, CH(I) . Molecular Chaperones and HSPs in Sugarcane and Eucalyptus. In: Asea, Alexzander A. A.,

Kaur, Punit, Calderwood, Stuart. (Org.). Heat Shock Proteins and Plants. 1ed.Londres: Springer International Publishing, 2016, v.

10, p. 1-390. [CHAPTER BOOK]

6. MENDES, J. S. ; SANTIAGO, A. S. ; TOLEDO, M. A. S. ; HORTA, M. A. C. ; SOUZA, A. A. ; TASIC, L. ; SOUZA, A. P. . In vitro

determination of extracellular proteins from Xylella fastidiosa. Frontiers in Microbiology (Online), 2016.

7. PONTES, J. G. M. ; BRASIL, A. J. M. ; CRUZ, G. C. F. ; SOUZA, R. N. ; TASIC, L. . 1-H NMR Metabolomic Profiling of Human

and Animal Blood Serum Samples. In: Paul Guest. (Org.). Multiplex Biomarker Techniques. 1ed.: , 2016, v. 1, p. 275-282.

[CHAPTER BOOK]

8. PONTES, JOÃO GUILHERME M. ; OHASHI, WILLIAM Y. ; BRASIL, ANTONIO J. M. ; FILGUEIRAS, PAULO R. ;

ESPÍNDOLA, ANA PAULA D. M. ; SILVA, JAQUELINE S. ; POPPI, RONEI J. ; COLETTA-FILHO, HELVÉCIO D. ; Tasic,

Ljubica . Metabolomics by NMR Spectroscopy in Plant Disease diagnostic: Huanglongbing as a Case Study. ChemistrySelect, v.

1, p. 1176-1178, 2016. http://dx.doi.org/10.1002/slct.201600064

9. QUEIROZ, V. L. ; AWAN, A. T. ; TASIC, L. . LOW COST-ENZYMES AND THEIR APPLICATIONS IN BIOENERGY SECTOR.

In: Gurpreet S. Dhillon; Surinder Kaur. (Org.). Agro-Industrial Wastes as Feedstock for Enzyme Production: Apply and Exploit

the Emerging and Valuable use Options of Waste Biomass. 1ed.Amsterdam, Boston, Heidelberg,: Academic Press, 2016, v. 1, p.

125-. [CHAPTER BOOK]

10. TASIC, L.; Mandic, B. ; BARROS, C. H. N. ; CYPRIANO, D. Z. ; STANISIC, D. ; SCHULTZ, L. G. ; SILVA, L. L. ; MARINO,

M. A. M. ; QUEIROZ, V. L. . EXPLORING BIOACTIVITY OF HESPERIDIN, NATURALLY OCCURRING FLAVANONE

GLYCOSIDE, ISOLATED FROM THE ORANGES. Citrus Fruits: Production, Consumption and Health Benefits. 1ed.: Nova

Science Publishers, 2016, v. 1, p. 25-75.[CHAPTER BOOK]

11. ZANPHORLIN, LETICIA M. ; LIMA, TATIANI B. ; WONG, MICHAEL J. ; BALBUENA, TIAGO S. ; MINETTI,

CONCEIÇÃO A. S. A. ; REMETA, DAVID P. ; YOUNG, JASON C. ; BARBOSA, LEANDRO R. S. ; GOZZO, FABIO C. ;

RAMOS, CARLOS H. I. . Heat shock protein 90 kDa Hsp90 has a second functional interaction site with the mitochondrial import

receptor Tom70. The Journal of Biological Chemistry (Print), p. jbc.M115.710137-18631, 2016.



1. BATISTA, FERNANDA A.H.; GAVA, LISANDRA M.; PINHEIRO, GLÁUCIA M. S.; RAMOS, CARLOS H.I.; BORGES, JÚLIO

C. (2015) From conformation to interaction: techniques to explore the Hsp70/Hsp90 network. Current Protein & Peptide Science. v. 16

(8), 735-753.

2. CYR, DOUGLAS M. AND RAMOS, CARLOS H. (2015). Specification of Hsp70 function by Type I and Type II Hsp40. In: The

Networking of Chaperones by Co-chaperones. Edit. Gregory Blatch and Adrienne Edkins. Springer Publishers ISBN: 978-3-319-

11730-0. DOI 10.1007/978-3-319-11731-7_4. Subcell Biochem. 2015;78:91-102. doi: 10.1007/978-3-319-11731-7_4. [CHAPTER

BOOK]

3. DORES-SILVA, P.R.; BARBOSA, L.R.S.; RAMOS, C.H.I.; BORGES, J.C. (2015) Human Mitochondrial Hsp70 (Mortalin):

Shedding Light on ATPase Activity, Interaction with Adenosine Nucleotides, Solution Structure and Domain Organization. PLOSOne.

10(1):e0117170. doi: 10.1371/journal.pone.0117170. eCollection 2015

4. FATTORI, J.; RODRIGUES, F. H. S.; PONTES, J. G. M.; ESPINDOLA, A. P. D. M.; TASIC, L. Monitoring Intermolecular And

Intramolecular Interactions By NMR. Spectroscopy. Applications of NMR Spectroscopy Volume 3, 1 Ed., 2015, p. 180-266.

[CHAPTER BOOK]

5. MARIÑO, M.; LOPES DA SILVA, L.; DURÁN, N.; TASIC, L. Enhanced Materials from Nature: Nanocellulose from Citrus Waste.

Molecules 2015, 20, 5908-5923.

6. Martins, Lucas Gelain; Figueiredo, Isis Martins; Cabeça, Luis Fernando; Tasic, Ljubica; Ramos, Carlos Henrique Inácio; Marsaioli,

Anita Jocelyne. Uso de Ressonância Magnética Nuclear de Alta Resolução para estudos de interações Receptores-Ligantes:

Fundamentos, Métodos e Aplicações. Biotecnologia aplicada à saúde: fundamentos e aplicações, volume 1 organizado por Rodrigo

Ribeiro Resende e Carlos Ricardo Soccol. -- São Paulo: Editora Edgard Blücher Ltda, 2015. ISBN 978-85-212-0896-9 [CHAPTER

BOOK]

7. MENDES J. S.; SANTIAGO, A. S.; TOLEDO, M. A. S.; ROSSELI-MURAI, L. K.; FAVARO, M. T. P.; SANTOS, C. A.; HORTA,

M. A. C.; CRUCELLO, A.; BELOTI, L. L.; ROMERO, F. V.; TASIC, L.; SOUZA, A. A.; SOUZA, A. P. VapD in Xylella fastidiosa

is a thermostable protein with ribonuclease activity. Plos One 2015, 10, e0145765, 2015.

8. MOKRY, DAVID Z; ABRAHAO, JOSIELLE; RAMOS, CARLOS H. I. (2015). Disaggregases, molecular chaperones that

resolubilize protein aggregates. Anais Academia Brasileira de Ciências. 87(2 Suppl 0):1273-1292

9. NESHICH, I. A, P.; NISHIMURA, L.: MORAES, F. R.; SALIM, J. A.; VILLALTA-ROMERO, F.; BORRO, L.; YANO, I. H.;

MAZONI, I.; TASIC, L.; JARDINE, J. G.; NESHICH, G. Computational biology tools for identifying specific ligand binding residues

for novel agrochemical and drug design. Current Protein and Peptide Science 2015, 16, 701-717.

10. OLIVEIRA, MAYCON C.; TEIXEIRA, RAPHAEL D.; ANDRADE, MAXUEL O.; PINHEIRO, GLAUCIA M. S.; RAMOS,

CARLOS H. I. AND FARAH, CHUCK S. (2015). Cooperative substrate binding by a diguanylate cyclase. J. Mol. Biol. 427, 415-432

11. ROJAS, L.; OLMEDO, H.; GARCIA-PINERES, A.; SILVEIRA, C.; TASIC, L.; FRAGA, F.; MONTERO, M. L. Simple route for

nano-Hydroxyapatite properties expansion. Biomedical Materials 2015, 10, 055015-055015.

12. SERAPHIM, THIAGO V.; GAVA, LISANDRA M.; MOKRY, DAVID Z.; CAGLIARI, THIAGO C.; BARBOSA, LEANDRO R.S.;

RAMOS, CARLOS H.I.; BORGES, JÚLIO C. (2015) The C-terminal region of the human p23 chaperone modulates its structure and

function. Archives of Biochemistry and Biophysics 565, 57–67.

13. SETHI, S.; HAYASHI, M.; SUSSULINI, A.; TASIC, L.; BRIETZKE, E. ANALYTICAL APPROACHES FOR LIPIDOMICS AND

ITS POTENTIAL APPLICATIONS IN NEUROPSYCHIATRIC DISORDERS. The World Journal of Biological Psychiatry 2015, 8,

1-49.


1. ARAUJO T.L., BORGES, J.C., RAMOS, C.H.I., MEYER-FERNANDES J.T., FOGUEL D., PALHANO F.L. (2014).

CONFORMATIONAL CHANGES IN HUMAN HSP70 INDUCED BY HIGH HYDROSTATIC PRESSURE PRODUCE OLIGOMERS

WITH ATPASE ACTIVITY BUT WITHOUT CHAPERONE ACTIVITY. BIOCHEMISTRY 53(18):2884-2889. *IN

COLLABORATION WITH FOGUEL (AL 2)

2. BERTAGNOLLI, C.; ESPINDOLA, A. P.; KLEINÜBING, S. J.; TASIC, L.; DA SILVA, M. G. C. Sargassum filipendula alginate from

Brazil: Seasonal influence and characteristics. Carbohydrate Polymers 2014, 111, 619-623.

3. CORREA, D.H.A., SILVA, S.L.F., RAMOS, C.H.I. (2014). Molecular cloning and protein

folding characterization of a predicted heme-binding globin in a sugar cane EST database. Jiomics. 4, 21-27. 10.5584/jiomics.v4i1.156





90

4. Hsp70 and Hsp90 in the Plasmodium and Leishmania Parasites. In: The Molecular Chaperones Interaction Networks in Protein Folding and

Degradation. Edit. Walid Houry. Springer Publishers ISBN: 978-1-4939-1129-5. DOI 10.1007/978-1-4939-1130-1_17 [CHAPTER BOOK]

5. MACIEL, BRUNA C. M.; BARBOSA, HERBERT S.; PESSÔA, GUSTAVO S.; SALAZAR, MARCELA M.; PEREIRA, GONÇALO A.

G.; GONÇALVES, DANIELI C.; RAMOS, CARLOS H. I; ARRUDA, MARCO A. Z. (2014) Comparative proteomics and metallomics

studies in Arabidopsis thaliana leaf tissues: evaluation of the selenium addition in transgenic and non-transgenic plants using two-

dimensional difference gel electrophoresis and laser ablation imaging. Proteomics. V.14, 904-912.

6. PAULA, A. J.; SILVEIRA, C.; MARTINEZ, D. S. T.; SOUZA FILHO, A. G.; VILLALTA ROMERO, F.; FONSECA, L.; TASIC, L.;

DURÁN, N.; ALVES, O. L.; Topography-driven bionano-interactions on colloidal silica nanoparticles. ACS Appl. Mater. Interfaces 2014, 6,

3437–3447.

7. PEREIRA, MICHELLE B. M.; SANTOS, ALINE M.; GONÇALVES, DANIELI C.; CARDOSO, ALISSON C.; CONSONNI, SILVIO R.;

GOZZO, FABIO C.; OLIVEIRA, PAULO S.; FIGUEIREDO, ALANA R.; TIROLI-CEPEDA, ANA O.; RAMOS, CARLOS H. I.; DE

THOMAZ, ANDRÉ A.; CESAR, CARLOS L.; FRANCHINI, KLEBER G. (2014) αB-crystallin interacts with and prevents stress-activated

proteolysis of focal adhesion kinase by calpain in cardiomyocytes. Nature Comm. 5, 5159. Doi 10.1038/ncomms6159

8. SERAPHIN, T.V.; RAMOS, C.H.I.; BORGES, J.C. (2014). The Interaction Networks of

9. TIROLI-CEPEDA, ANA O.; LIMA, TATIANI B.; GOZZO, FÁBIO C.; RAMOS, CARLOS H.I. (2014). Structural and functional

characterization of the chaperone Hsp70 from sugarcane. Insights into conformational changes during cycling from cross-linking/mass

spectrometry assays. J. Proteomics. 104(2) 48-56

10. ZANPHORLIN, LETICIA M; ALVES, FERNANDA R; RAMOS, CARLOS HENRIQUE (2014). The effect of celastrol, a triterpene with

antitumorogenic activity, on conformational and functional aspects of human 90 kDa heat shock protein Hsp90, a chaperone implicated in the

stabilization of the tumor phenotype. Biochimica et Biophysica Acta General Subjects. 1840. 3145-3152.


1. AWAN, A. T.; TSUKAMOTO, J.; TASIC, L.; Orange waste as a biomass for 2G-ethanol production using low cost enzymes and co-culture

fermentation. RSC Advances 2013, 3, 25071-25078.

2. DA SILVA, VIVIANE C.H.; CAGLIARI, THIAGO C.; LIMA, TATIANI B.; GOZZO, FÁBIO C.; RAMOS, CARLOS H.I. (2013).

Conformational and functional studies of a cytosolic 90 kDa heat shock protein Hsp90 from sugarcane. Plant Physiol. Biochem. 68, 16-22.

3. DORES-SILVA, PAULO R; MINARI, KARINE; RAMOS, CARLOS H; BARBOSA, LEANDRO R; BORGES, JULIO CESAR (2013).

Structural and stability studies of the human mtHsp70-escort protein 1: an essential mortalin co-chaperone. Int. J. Biol. Macromol. 56, 140-

148.

4. DURÁN, N.; TSUKAMOTO, J.; AWAN, A. T.; CYPRIANO, D. Z.; TASIC, L. Nanocellulose and bioethanol production from orange

waste. Valorización de Residuos: Oportunidad para la innovación. 1ed.Temuco: Universidade de La Frontera, 2013, v. 1, p. 111-117.

[CHAPTER BOOK]

5. MILLAN, I.C.R., SQUILLACE, A.L.A, GAVA, L.M., RAMOS, C.H.I. (2013). The stability of wild-type and deletion mutants of human C-

terminus Hsp70-interacting protein (CHIP). Prot Pep Lett. 20(5), 524-529.

6. TOLEDO, M.A.S.; SANTOS, C.A.; MENDES, J.S.; PELLOSO, A.C.; BELOTI, L.L.; CRUCELLO, A.; FAVARO, M.T.P.; SANTIAGO,

A.S.; SCHNEIDER, D.R.S.; SARAIVA, A.M.; STACH-MACHADO, D.R.; SOUZA, A.A.; TRIVELLA, D.B.B.; APARICIO, R.; TASIC,

L.; AZZONI, A.R.; SOUZA, A.P. Small-angle X-ray scattering and in silico modeling approaches for the accurate functional annotation of

an LysR-type transcriptional regulator. Biochimica et Biophysica Acta. Proteins and Proteomics 2013, 1834, 697-707.

7. TSUKAMOTO, J.; DURÁN, N.; TASIC, L.; Nanocellulose and bioethanol production from orange waste using isolated micoorganisms.

Journal of the Brazilian Chemical Society 2013, 24, 1537-1543.

8. ZAMPIERI, D.; SANTOS, V.G.; BRAGA, P.A.; FERREIRA, C.R.; BALLOTTIN, D.; TASIC, L.; BASSO, A.C.; SANCHES, B.V.;

PONTES, J.H.; DA SILVA, B.P.; GARBOGGINI, F.F.; EBERLIN, M.N.; TATA, A. Microorganisms in cryopreserved semen and culture

media used in the in vitro production (IVP) of bovine embryos identified by matrix-assisted laser desorption ionization mass spectrometry

(MALDI-MS). Theriogenology 2013, 88, 337-345.

Patents and processes developed by AL7, from 2013 to 2016:

1. TASIC, L.; Poppi, R. J.; Brietzke, E.; Hayashi, M. MÉTODO DE IDENTIFICAÇÃO POR RESSONÂNCIA MAGNÉTICA NUCLEAR

(RMN) E QUMIOMETRIA DE BIOMARCADORES PARA DOENÇAS MENTAIS GRAVES E USOS DE MESMOS. Patent: Privilege of

Innovation. Register number: BR102015031930, Date of patent filing: 15/12/2015, INPI - Instituto Nacional da Propriedade Industrial.

2. TASIC, L.; Ballottin, D. P. M.; Marcato P. D.; Durán, N.; Tsukamoto, J.; PROCESS OF PRODUCTION OF SILVER NANOPARTICLES

STABILIZED BY PROTEINS IN THE PRODUCTION OF ANTIMICROBIAL TEXTILE PRODUCTS AND THE TREATMENT OF

PRODUCED EFFLUENTS. Patent: Privilege of Innovation. Register number: PI06056814, Date of patent filing: 26/02/2015, INPI -

Instituto Nacional da Propriedade Industrial.

3. TASIC, L.; Tsukamoto, J.; AWAN, A. T.; Durán, N. PROCESS OF OBTAINING BIOETHANOL, ESPERIDINE AND

NANOCELLULOSE FROM ORANGE BAG. Patent: Privilege of Innovation Register number: BR1020130325856, Date of patent filing:

18/12/2013, INPI - Instituto Nacional da Propriedade Industrial.


http://www.ncbi.nlm.nih.gov/pubmed?term=Zampieri%20D%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Santos%20VG%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Braga%20PA%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Ferreira%20CR%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Ballottin%20D%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Tasic%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Basso%20AC%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Sanches%20BV%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Pontes%20JH%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=da%20Silva%20BP%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Garboggini%20FF%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Eberlin%20MN%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed?term=Tata%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23756041

http://www.ncbi.nlm.nih.gov/pubmed/23756041


91

AL 8 - Associated Laboratory of Macromolecules

Crystallization

- Coodinator:

Marcelo Santos Castilho - Universidade Federal de Bahia (UFBA)

- Researchers from national institutions: Tânia Fraga Barros – FF/UFBA.


Lara Maria Brito Cunha Ribeiro (UEFS)

Thamires Quadros Froes (UEFS)

Camila Carane Bitencourt Brito (UEFS)

Odailson Santos Paz (UEFS)

Ricardo Lustosa Brito (UFBA)


Lenisa Dandara Santos (UFBA)

Aline Grazielle Magalhães Quadros (UFBA)

Fábio Mota Silva (UFBA)

Carolina do Rosário Esteves Guimarães (UFBA)

Amanda Barbara Moscozo Araújo da Cruz (UFBA)

Laís Ximenes Farias (UFBA)


Bianca Chaves Trindade (UFBA)

Michell Bruno Lago da Silva (UFBA)

Raíssa Rayane Santos Laurindo Caldas (UFBA)

Felipe Oliveira Pinto (UFBA)

Lucas de Jesus Santos (UFBA)

The Associate laboratory has its research

interests towards enzymes that are

considered as good targets for either

antifugal therapy or neglected disease drug

development. In the last four years, several

efforts have been made into this purpose.


results obtained during the 2013 - 2016

period:

Development of a new class of non-

competitive LmPTR1 inhibitors.

Leishmania major, as other protozoan

parasites, plague human kind since pre-

historic times but it remains a worldwide

ailment for which the therapeutic arsenal

remains scarce. Although L. major is

pteridine- and purine- auxotroph, well

established folate biosynthesis inhibitors,

such as methotrexate, have poor effect

over the parasite survival. The lack of

efficiency is related to an alternative

biochemical pathway in which pteridine

reductase 1 (PTR1) plays a major role. For

this reason, this enzyme has been

considered a promising target for anti-

leishmanial drug development and several

inhibitors that share the substrate scaffold

have been reported. The structure-guided

approach employed in this work proved

effective to identify a novel class of

LmPTR1 inhibitors whose scaffold is

completely different from the molecules

previously reported. We employed the

thiazolidinone ring as a bioisosteric

replacement for pteridine/purine ring.

Among seven novel thiazolidine-2,4-dione

derivatives reported herein, 2d was


92

identified as the most promising lead by

thermal shift assays (∆Tm= 11 ºC, p=

0,01). Kinetic assays reveal that 2d has

IC50 = 44.67± 1.74 µM and shows a

noncompetitive behavior. This information

guided docking studies and molecular

dynamics simulations (50000 ps) that

supports 2d putative binding profile (H-

bonding to Ser- 111 and Leu-66) and shall

be useful to design more potent inhibitors

(Figure 1).

Fig. 1. Putative binding profile of 2d towards LmPTR1 NADPH binding site. (A) best ranked pose

according to Surflex-Dock. (B) representative conformation of 2D according to MD simulations (50000 ps).

The NADPH binding site residues are depicted in line, whereas 2d is depicted in stick model. The hydrogen

bonds are displayed as dashed line and distances are measured in angstroms. The figure was generated

using the PyMOL 1.3 software.

Studies on novel targets in Alzheimer

disease

β-secretase (BACE-1) plays a pivotal role

in the β-Amyloid plaques formation,

which is responsible for progressive

cognitive and memory loss commonly

found in Alzheimer disease patients. As a

consequence, it has been considered as a

good target for drug development efforts.

Early work focused on the synthesis of

peptidomimetics, but poor

pharmacokinetics profile prevented

advancing lead compounds to clinical

trials. As an alternative, aminoimidazoles,

aminohydantoins and aminopyridines

derivatives that inhibit BACE-1 were

designed. Herein we report statistically

sound descriptor- based (r2 = 0.87, q2 =

0.85, 6 PCs) and fragment-based (r2 =

0.91, q2 = 0.84, 6 PCs) QSAR models,

that show high predictive ability (r2pred =

0.84, averaged r2m=0.78) and underscore

polar interactions that are important for

BACE-1 inhibition.

Investigations on antifungal compounds

Fungal infections have become an

increasing health problem, especially for

immunocompromised patients.

Unfortunately, the gold standard

prophylactic therapy for such ailment is

based on azole derivatives, which are

fungistatic rather than fungicidal against

C. neoformans and cause hepatotoxicity.

Aiming at circumvent these problems,

non-azole CYP51 inhibitors were

designed. Herein a comprehensive

structure-activity relationships study was

carried out for a dataset of 110 molecules

by means of hologram- and descriptor-

based QSAR studies. The best descriptor-

based QSAR model (r2 = 0.92, q2 = 0.90, 6

LVs and r2pred =0.86) suggests that

resonance effects (ESpm08r) play a major

role for antifungal activity. The hologram-

based QSAR (r2 = 0.87, q2 = 0.81, 6 LVs

and r2pred = 0.84) supports this hypothesis

and hints at steric properties that should

also contribute to non-azole inhibitors

potency (Figure 2). The insights provided

by the integrated analysis of QSAR


93

models, along with their good predictive

power prove their usefulness to future

drug design efforts.

Figure 2. Contribution for weak (upper panel,

cpd 06 pMIC80 = -2.02) and potent (lower panel,

cpd 35 pMIC80 = 0.60) non-azole antifungals

according to the best HQSAR model.

Also, there has been an upsurge of

cryptococosis infections that poorly

respond to fluconazole (first choice drug).

Hence, it is paramount to investigate the

chemical properties of azole derivatives

that are active against resistant C.

neoformans. In order to achieve this goal,

the susceptibility profile of a clinical

isolate of resistant C. neoformans against

33 commercial azole derivatives was

evaluated along with their potency

(minimum inhibitory concentration, MIC).

These data were employed to build

SIMCA (soft independent modeling of

class analogies) models that pinpoint the

importance of electronic features (JGI10)

to separate active from inactive

compounds and hologram-QSAR models

that have good fit but insufficient

predictive power (HQSAR, r2 = 0.85, q2 =

0.35 and r2 pred = 0.38). Conversely, 2D

QSAR models built from topological

descriptors improved the statistical quality

(r2 = 0.95, q2 = 0.86, r2 pred = 0.72) and

highlight that charge distribution (GGI1)

and topological electronegativity

(GATS1e and MATS2e) should be

modulated to overcome the C. neoformans

resistance.

AL X main publications in 2016: 1. COSTA, RAFAEL S. ; LINS, MANUELA O. ; HYARIC, MIREILLE LE ; BARROS, TÂNIA F. ; VELOZO, EUDES S. . In vitro

antibacterial effects of Zanthoxylum tingoassuiba root bark extracts and two of its alkaloids against multiresistant Staphylococcus

aureus. Revista Brasileira de Farmacognosia (Impresso), v. 00, p. 00-06, 2016. http://dx.doi.org/10.1016/j.bjp.2016.11.001

2. LEITE, FRANCO HENRIQUE A. ; SANTIAGO, PRISCILA BRANDÃO GOMES DA SILVA ; FROES, THAMIRES QUADROS ;

DA SILVA FILHO, JOÃO ; DA SILVA, SUELLEN GONÇALVES ; XIMENES, RAFAEL M. ; DE FARIA, ANTÔNIO RODOLFO

; BRONDANI, DALCI JOSÉ ; DE ALBUQUERQUE, JULIANNA F.C. ; CASTILHO, MARCELO SANTOS . Structure-guided

discovery of thiazolidine-2,4-dione derivatives as a novel class of Leishmania major pteridine reductase 1 inhibitors. European Journal

of Medicinal Chemistry, v. 123, p. 639-648, 2016. http://dx.doi.org/10.1016/j.ejmech.2016.07.060

AL X main publications in 2015: 1. TAVARES, ELIANDRO REIS ; AZEVEDO, CAROLINE SOUZA ; PANAGIO, LUCIANO APARECIDO ; PELISSON,

MARSILENI ; PINGE-FILHO, PHILENO ; VENANCIO, EMERSON JOSÉ ; BARROS, TÂNIA FRAGA ; YAMADA-OGATTA,

SUELI FUMIE ; YAMAUCHI, LUCY MEGUMI . Accurate and sensitive real-time PCR assays using intergenic spacer 1 region to

differentiate Cryptococcus gattii sensu lato and Cryptococcus neoformans sensu lato. Medical Mycology (Oxford. Print), v. 00, p.

myv078-8, 2015. http://dx.doi.org/10.1093/mmy/myv078

AL X main publications in 2014: 2. Cruz, D. S. ; Castilho, Marcelo S . 2D QSAR Studies on Series of Human Beta-secretase (BACE-1) Inhibitors. Medicinal Chemistry

(Hilversum), v. 10, p. 162-173, 2014. http://dx.doi.org/10.2174/15734064113099990002

3. PACHECO, A. G. M. ; Castilho, Marcelo S ; LUCCHESE, A. M. ; PEREIRA, G. ; TARANTO, A. G. . Comparative modeling studies

of lanosterol 14-α demethylase of Moniliophthora perniciosa. BBR - Biochemistry and Biotechnology Reports, v. 2, p. 1-7, 2014. DOI

10.5433/2316-5200.2013v2n4p8

4. SALES, E. M. ; BARROS, T F ; VELOZO, ES . Biotransformation of coumarins by Saccharomyces cerevisiae. World Journal of

Pharmacy and Pharmaceutical Sciences v. 3 (12), p. 209-216, 2014. http://www.wjpps.com/download/article/1417415531.pdf

AL X main publications in 2013: 1. Freitas, Humberto F ; Barros, Tânia F. ; Castilho, Marcelo S . 2D Chemometric Studies of a Series of Azole Derivatives Active against

Fluconazole-Resistant Cryptococcus gattii. Journal of the Brazilian Chemical Society (Impresso), v. 24, p. 962-972, 2013.

http://dx.doi.org/10.5935/0103-5053.20130122

2. Ribeiro, L. M. B. C. ; FREITAS, H. F. ; Castilho, Marcelo S . Hologram- and Descriptor-Based QSAR Studies for a Series of Non-

Azoles Derivatives Active Against. Journal of the Brazilian Chemical Society (Impresso), v. 24, p. 1623-1634, 2013.

http://dx.doi.org/10.5935/0103-5053.20130207

3. TUNES, ALESSANDRO ; REIS, JOICE NEVES ; TERSE, REGINA ; SANTANA, MARIA ANGÉLICA ; DINIZ, ANA LÚCIA ;

BARROS, TÂNIA FRAGA ; LEAL, ANA KARINA SOUZA ; PAIXÃO, VILMA ; GRASSI, MARIA FERNANDA RIOS .

Microbiology of the middle meatus compared to sputum in young patients with cystic fibrosis from Bahia - Brazil. The Brazilian

Journal of Infectious Diseases (Impresso), v. 13, p. S1413, 2013. http://dx.doi.org/10.1016/j.bjid.2013.07.006

http://dx.doi.org/10.1016/j.bjp.2016.11.001

http://dx.doi.org/10.1016/j.ejmech.2016.07.060

http://dx.doi.org/10.1093/mmy/myv078

http://dx.doi.org/10.2174/15734064113099990002

http://www.wjpps.com/download/article/1417415531.pdf

http://dx.doi.org/10.5935/0103-5053.20130122

http://dx.doi.org/10.5935/0103-5053.20130207

http://dx.doi.org/10.1016/j.bjid.2013.07.006


94

AL 9 - Associate Laboratory of Cellular Ultrastructure

Hertha Meyer

- Coordinator:

Wanderley de Souza – IBCCF/UFRJ.


Tecia Maria Ulisses de Carvalho – IBCCF/UFRJ;

Rossiane Vommaro – IBCCF/UFRJ;

Maria Cristina Motta – IBCCF/UFRJ;

Márcia Attias– IBCCF/UFRJ;

Narcisa Leal da Cunha e Silva – IBCCF/UFRJ;

Kildare Miranda – IBCCF/UFRJ;

Juliany Cola Fernandes Rodrigues – IBCCF/UFRJ;

Susana Frasés Carvajal – IBCCF/UFRJ;

Emile Barrias – Inmetro;

Ana Paula Rocha Gadelha – Inmetro.

- Researchers collaborators from international institutions:

Carlos Robello, Instituto Pasteur de Montevidéu, Uruguai,

Patrícia Romano, Instituto de Histologia, Univ. Nacional de Cuyo, Mendoza, Argentina;

Francisco Barrantes, Universidad Catolica de Buenos Aires, Argentina;

Maria Corvi, Instituto Tecnológico de Chascomús, Argentina;

Theodora Calogeropoulou, Instituto Helênico, Atenas, Grécia;

Roberto Docampo, Univ. Georgia, Athens, USA;

Peter Ingran, North Carolina University, USA;

Helmut Plattner, Univ. Kontanz, Alemanha;

Keith Gull, Univ. Oxford, Inglaterra;

Sue Vaughan, Univ. Oxford Brookes, Inglaterra;

F. Bracher, Univ. Munique, Alemanha.


Aline Araújo Zuma,

Aline Cristina de Abreu Moreira

de Souza, Claudia Maia

Brigagão,

Erica Martins Duarte, Joseane

Godinho, Juliana Cunha Vidal,

Lucio Ayres Caldas,

Miria Gomes Pereira,

Victor Midlej, Phercycles Veiga.


Aline Araujo Alves,

Ana Carolina Loyola Monteiro,

Camila Hubner Costabile

Wendt,

Carolina de Lima Alcantara,

Lissa Catherine Reignault de

Barros Moreira,

Juliana Portes,

Roberta Fernandes Pinto,

Sara Teixeira de Macedo Silva,

Sílvia Nunes Quintal,

Viviane Sant’Anna,

Wendell Girard Dias.


Glauber Ribeiro de Sousa

Araújo,

Brunno Verçoza,

Jean Oliveira Santos,

Leonardo Davi Veiga,

Verônica Santos,

Noêmia Rodrigues,

Luis Otávio da Silva Pacheco.


Alexia Achilles,

Aline Pereira,

Ana Paula Pereira,

Camila Gonçalves,

Diego Lelis,

Diana Dolzani,

Douglas Monteiro,

Eduardo Glejzer,

Felipe Louzada Rubim,

Felipe Simplicio,

Fernanda Souza Cruz,

Fernanda Pereira Bortolami,

- Undergraduate students

(continuing):

Gabrielle Lacerda,

Igor Cardoso,

Juliana Alves,

Maíra Carias,

Marcus Rodrigues,

Marco Antonio Ferreira Motta,

Pedro Gralha,

Thallita Coutinho,

Vinicius Alves.

- Technicians:

Ana Cristina Dore,

Camila Cristina Silva,

Noêmia Rodrigues

Luis Otavio Pacheco,

Rafael Fantesia,

Verônica Santos,

Paulo Crepaldi, Raquel Rachid,

Daniel Gonçalves Iucif Vieira,

Luis Sérgio Cordeiro,

Fernando Pereira de Almeida.


95

We will make a brief comment on three

distinct areas of research of the laboratory

emphasizing only those results we consider

most relevant, as well as good examples of

what we are doing. Three different areas

will be covered:

- Cell organization;

- Host cell-parasite interaction;

- Experimental chemotherapy.

Cell organization

The analysis of the structural organization

of parasitic protozoa belonging to several

taxonomical groups has been the focus of

attention of several members of the group.

A few examples will be commented.

1- First, we analyzed in detail the process

of biogenesis of the flagellum of the

amastigote form of Leishmania

amazonensis, which takes place when

they transform into promastigotes.

Interesting results were obtained,

especially in relation to the appearance

of the so-called intraflagellar particles.

2- Second, using both electron microscopy

tomography and focused ion beam it

was possible to obtain 3-D

reconstruction of the whole cell. As an

example in T. cruzi new sets of

cytoplasmic microtubules were found.

In addition, the whole cytostome-

cytopharinx complex was visualized in

detail for the first time. The behavior of

these structures during the process of

epimastigote to trypomastigote

transformation, as well as during the

different phases of the cell cycle, were

analyzed in some detail (Figure 1).

Figure 1 - The distribution of microtubules along the T. cruzi epimastigote cytopharinx. Serial tomograms of

an early G2-phase (1N1K2F) epimastigote that had taken up Tf-Au for 15 minutes, showing the positioning of

microtubules along the cytopharinx. (A) View of the 3D model of Tomo 2 showing the beginning of the

microtubule quartet (Q1 to Q4, blue) that follows the path of the preoral ridge (purple), and then bends into

the cytoplasm, accompanying the cytostome/cytopharinx (pink). A microtubule triplet (T1 to T3, green)

originates from a position adjacent to the opening of the cytostome and also accompanies the cytopharinx. (B-

F) Virtual slices of the tomogram representing the regions indicated in A. (B) The microtubule quartet (blue

arrows) can be seen lining the cytopharinx (Cy) and the preoral ridge (purple contour). In D we can see the

full set of microtubules around the cytopharinx and a vesicle (black arrowhead) containing Tf-Au particles

(black dots) close to the naked side of the cytopharinx. This vesicle can also be seen in yellow in the model in G

and H. Other membrane-bound compartments were observed close to the naked side of the cytopharinx

(asterisks in E and F). As the cytopharinx became thinner, running deeper into the cell, microtubules Q3 from

the quartet (E) and T1 from the triplet (F) disappeared. The light blue arrow and the dark green arrow in E

and F indicate the very end of these microtubules, respectively. G) Back view of the model in A, where the

positioning of/ distribution of microtubules at the flagellar pocket, preoral ridge and the cytostome can be

better visualized. I) At the most distal portion of the cytopharinx (relative to the cytostome) only five

microtubules were seen around this structure, arranged in a half-moon shape. K (kinetoplast), M

(mitochondrion), G (Golgi complex), New Flagellum (orange), Old Flagellum (light blue). Scale bars: 200 nm


96

3- Third, using a similar approach, it

was possible to obtain new

information on the mitosomes,

encystation vesicles and

carbohydrate-containing vesicles

during the cell cycle and the

encystation process in Giardia

intestinalis.

4- Fourth, new relevant information

were obtained about the process of

formation of food vacuoles in the

different intraerythrocytic stages of

Plasmodium chabaudi (Figure. 2).

Figure 2 - Spatial distribution of hemozoin crystals in the Plasmodium chabaudi schizont. Two food vacuoles

(A and B, black arrowheads) and a cytostome (B, arrow) are observed throughout z slices (A and B). Three-

dimensional modeling (C) allowed a better analysis of the food vacuole dispersion and the small cytostome

structure (C, arrow). Most of the crystals were located inside large food vacuoles (D–E). Sections of the larger

food vacuole display its internal organization (F). One of the smaller food vacuoles had a polyhedral

membranous structure in its interior (F and G, arrowhead). This membrane occupied a small volume and was

close to the hemozoin crystals (H, arrowhead). Yellow: parasite membrane, dark blue: nucleus, light blue: food

vacuole, purple: hemozoin crystals, red: cytostome. Scale bar: 500 nm (A–C), 200 nm (D–F), 100 nm (G and

H).


97

5- Fifth, using high resolution scanning

electron microscopy and Helium ions

scanning microscopy new cytoskeleton

structures were described in Giardia

intestinalis and Tritrichomonas foetus

(Figure 3)

Fig. 3 - The dorsal (a–d) side of the Giardia lamblia

trophozoite, as seen using HIM. (a) Cytoplasmic

filaments (arrow) contacting cytoskeletal

structures, such as the median body (MB). (b) Is a

high magnification of (a). It is possible to observe a

ring array (arrowhead). (c) HIM images revealed a

lattice-like array material covering the

microtubular sheets (⁄) of funis. (d) Small bridges

interconnected the lateral microtubules of the funis

(arrowheads). Bars: 2 lm (a); 100 nm (b); 200 nm (c

and d).

Host cell-parasite interaction

A second area of work of our group is the

analysis of the process of interaction of

parasitic protozoa with host cells. Again,

several approaches have been used.

1- First, using specific inhibitors we have

shown that T. cruzi and T. gondii may

gain access to the host cells using

several mechanisms, including:

(a) the use of lipid raft regions,

(b) clathrin-mediated processes,

(c) macropinocytosis, and

(d) phagocytosis.

All these processes were further

characterized by electron microscopy

immunocytochemistry.

2- Second, using inhibitors, we also

characterized the process of egress of T.

gondii from the host cell, which takes

place at the end of the intracellular

cycle.

3- Third, we characterized a strain of T.

gondii that is highly cystogenic in vitro.

This experimental system has being used

to analyze in detail the biogenesis of the

cyst wall (Figure 4).

Fig. 4 - Fluorescence microscopy of LLC-MK2 cells

infected by T. gondii, EGS strain. After 4 four days

of infection, we could simultaneously find cysts

containing bradizoytes (green, cyst wall stained

with Dolichos biflorus lectin – FITC ) and

tachizoytes containing vacuoles (red, antibody

staining for surface protein SAG-1).

4- Fourth, using high-resolution scanning

electron microscopy and Helium ion

microscopy we obtained images that

showed new information on the

organization of the parasitophorous

vacuole containg T.gondii (Figure 5).


98

Fig. 5 - Helium Ion Microscopy of a Toxoplasma gondii inside a vacuole. Soon after invasion, secretion of dense

granules leads to the formation of the intravacuolar network seen as tubules connecting the parasite to the

vacuolar membrane. Scale bar: 500 nm.

5- Fifth, using immunocytochemistry and

3-D reconstruction we obtained new data

on the participation of Galectin-3 on the

fate of the parasitophorous vacuole

containg T.cruzi.

6- Sixth, we obtained a considerable

amount of data on:

(a) The process of release of

microvesicles (exosomes and ectosomes) of

T. cruzi,

(b) Characterization of small

microRNAs and proteins present in the

vesicles,

(c) The interaction of the vesicles

with the parasites as well as with the host

cells, and

(d) The role of these vesicles on the

modulation of the infection process.

Experimental chemotherapy

A third area of intense work is related with

experimental chemotherapy, aiming the

identification and test of new compounds

with activity against several parasitic

protozoa. In this area, two major

experimental advances worth to be pointed

out.

1- First, the introduction of a high

throughput process of drug screening

allowing the test of hundreds of

compounds in a short time.

2- Second, the production of parasites (T.

cruzi and Leishmania) expressing

luciferase which opens the possibility to

follow the fate of parasites in control and

drug-treated mice infected with the

parasites.

We have tested a large number of

compounds in vitro and some of them were

highly active displaying IC50 at low

submicromolar and even at nanomolar

concentrations for T. cruzi and Leishmania.

The most promising compounds are sirtuin

inhibitors, squalene synthase inhibitors, and

phospholipid analogues, especially some

hybrid compounds obtained with the

incorporation of dinitroaniline to the lead

compound. These compounds are being

tested in vivo using experimentally infected

mice. Compounds that interfere with the

replication of the Kinetoplast DNA are also

being tested.

In relation to T. gondii promising

results have been obtained:

(a) with ciprofloxacin derivatives,

(b) Triclosan,

(c) nanoencapsulation of

pyrimetamine and the association of

different compounds.


99


1. ALCANTARA, CAROLINA DE L. ; VIDAL, JULIANA C. ; DE SOUZA, WANDERLEY ; CUNHA-E-SILVA, NARCISA L. . The cytostome-

cytopharynx complex of epimastigotes disassembles during cell division. Journal of Cell Science, v. 129, p. jcs.187419, 2016.

doi: 10.1242/jcs.187419

2. ATTIAS, MÁRCIA ; SATO, LYSLAINE H. ; FERREIRA, ROBSON C. ; TAKATA, CARMEN S. A. ; CAMPANER, MARTA ; CAMARGO,

ERNEY P. ; TEIXEIRA, MARTA M. G. ; DE SOUZA, WANDERLEY . Developmental and Ultrastructural Characterization and Phylogenetic

Analysis of Trypanosoma herthameyeri n. sp of Brazilian Leptodactilydae Frogs. The Journal of Eukaryotic Microbiology, v. xx, p. n/a-n/a, 2016.

http://onlinelibrary.wiley.com/doi/10.1111/jeu.12310/abstract;jsessionid=F223463FF0F740CE349DC5F15FA3B6DE.f04t03

3. AUGUSTO, INGRID ; MONTEIRO, DOUGLAS ; Girard-Dias, Wendell ; DOS SANTOS, THAISA OLIVEIRA ; ROSA BELMONTE, SIMONE

LETÍCIA ; PINTO DE OLIVEIRA, JAIRO ; MAUAD, HELDER ; DA SILVA PACHECO, MARCOS ; LENZ, DOMINIK ; STEFANON

BITTENCOURT, ATHELSON ; VALENTIM NOGUEIRA, BRENO ; LOPES DOS SANTOS, JORGE ROBERTO ; Miranda, Kildare ;

GUIMARÃES, MARCO CESAR CUNEGUNDES . Virtual Reconstruction and Three-Dimensional Printing of Blood Cells as a Tool in Cell

Biology Education. Plos One, v. 11, p. e0161184, 2016. http://dx.doi.org/10.1371/journal.pone.0161184

4. BORBA-SANTOS, LUANA P. ; Visbal, Gonzalo ; GAGINI, THALITA ; RODRIGUES, ANDERSON M. ; DE CAMARGO, ZOILO P. ; LOPES-

BEZERRA, LEILA M. ; Ishida, Kelly ; de Souza, Wanderley ; Rozental, Sonia . -24-Sterol Methyltransferase Plays an Important Role in the Growth

and Development of Sporothrix schenckii and Sporothrix brasiliensis. Frontiers in Microbiology (Online), v. 7, p. 311, 2016.

5. BORBA-SANTOS, LUANA PEREIRA ; Ishida, Kelly ; CALOGEROPOULOU, THEODORA ; Souza, Wanderley de ; Rozental, Sonia .

Adamantylidene-substituted alkylphosphocholine TCAN26 is more active against Sporothrix schenckii than miltefosine. Memórias do Instituto

Oswaldo Cruz (Online), v. 111, p. 523-527, 2016.

6. BRAGA, RAQUEL RENNÓ ; ALMEIDA, LUCIANA ; Guerreiro, Luiz Henrique ; TINOCO, PRISCILLA ; MIRANDA, KILDARE R. ; BRAGA,

CAROLINA A. ; GADELHA, ANA PAULA ; GARCIA, SHEILA ; LIMA, LUIS MAURICIO T. R. . Molecular confinement of human amylin in

lipidic nanoparticles. Journal of Liposome Research, v. 1, p. 1-11, 2016. http://dx.doi.org/10.3109/08982104.2015.1076462

7. CABALLERO, MARINA C. ; ALONSO, ANDRÉS M. ; DENG, BIN ; ATTIAS, MARCIA ; de Souza, Wanderley ; CORVI, MARÍA M. .

Identification of new palmitoylated proteins in Toxoplasma gondii. Biochimica et Biophysica Acta. Proteins and Proteomics, v. 1864, p. 400-408,

2016. http://dx.doi.org/10.1016/j.bbapap.2016.01.010

8. CALDAS, LUCIO AYRES ; SOARES, LEANDRO LEMGRUBER ; SEABRA, SERGIO ; ATTIAS, MARCIA ; DE SOUZA, WANDERLEY .

Monitoring of dynamin during the cell cycle. Pathogens and Disease, 2016. http://femspd.oxfordjournals.org/content/74/9/ftw108

9. CATTA-PRETA, CAROLINA MOURA COSTA ; PASCOALINO, BRUNO DOS SANTOS ; DE SOUZA, WANDERLEY ; MOTTRAM,

JEREMY C. ; MOTTA, MARIA CRISTINA M. ; SCHENKMAN, SERGIO . Reduction of Tubulin Expression in Angomonas deanei by RNAi

Modifies the Ultrastructure of the Trypanosomatid Protozoan and Impairs Division of Its Endosymbiotic Bacterium. The Journal of Eukaryotic

Microbiology, v. 2016, p. 1-10, 2016.

10. CORREA, DELEON NASCIMENTO ; SCHMIDT, EDUARDO MORGADO ; FRANCO, MARCOS FERNANDO ; ZACCA, JORGE JARDIM ;

DE CARVALHO ROCHA, WERICKSON FORTUNATO ; DE PAULA BARBOSA, ANTONY ; BORGES, RODRIGO ; de Souza, Wanderley ;

EBERLIN, MARCOS NOGUEIRA . Analyzing Brazilian Driver?s License Authenticity by Easy Ambient Sonic-Spray Ionization Mass

Spectrometry. American Journal of Analytical Chemistry, v. 07, p. 342-350, 2016.

11. CORREA, DELEON NASCIMENTO ; ZACCA, JORGE JARDIM ; ROCHA, WERICKSON FORTUNATO DE CARVALHO ; BORGES,

RODRIGO ; de Souza, Wanderley ; AUGUSTI, RODINEI ; EBERLIN, MARCOS NOGUEIRA ; VENDRAMINI, PEDRO HENRIQUE . Anti-theft

device staining on banknotes detected by mass spectrometry imaging. Forensic Science International, v. 260, p. 22-26, 2016.

12. DA SILVA FERREIRA, VERONICA ; CONZ, MATEUS EUGENIO FERREIRA ; LIMA, LUÍS MAURÍCIO T.R. ; FRASÉS, SUSANA ; de

Souza, Wanderley ; SANT?ANNA, CELSO . Green production of microalgae-based silver chloride nanoparticles with antimicrobial activity against

pathogenic bacteria. Enzyme and Microbial Technology, v. xx, p. 1-5, 2016.

13. EUGENIO, MATEUS ; MÜLLER, NATHALIA ; FRASÉS, SUSANA ; ALMEIDA-PAES, RODRIGO ; LIMA, LUÍS MAURÍCIO T. R. ;

Lemgruber, Leandro ; FARINA, MARCOS ; de Souza, Wanderley ; Sant'anna, Celso . Yeast-derived biosynthesis of silver/silver chloride

nanoparticles and their antiproliferative activity against bacteria. RSC Advances: an international journal to further the chemical sciences, v. 6, p.

9893-9904, 2016.

14. GONÇALVES JP, OLIVEIRA-MENEZES A, MALDONADO A JUNIOR, CARVALHO TM, DE SOUZA W.Ultrastructural and cytochemical

characterization of T1 and T2 secretory bodies from the tegument of Echinostomaparaensei. Micron. 2016 Jan;80:59-65. doi:

10.1016/j.micron.2015.09.008

15. HOLANDINO, CARLA ; TEIXEIRA, CESAR AUGUSTO ANTUNES ; DE OLIVEIRA, FELIPE ALVES GOMES ; BARBOSA, GLEYCE

MORENO ; SIQUEIRA, CAMILA MONTEIRO ; MESSEDER, DOUGLAS JARDIM ; DE AGUIAR, FERNANDA SILVA ; DA VEIGA,

VENICIO FEO ; Girard-Dias, Wendell ; Miranda, Kildare ; GALINA, ANTONIO ; CAPELLA, MARCIA ALVES MARQUES ; MORALES,

MARCELO MARCOS . Direct electric current treatment modifies mitochondrial function and lipid body content in the A549 cancer cell line.

Bioelectrochemistry (Amsterdam), v. 1, p. 00-00, 2016. http://dx.doi.org/10.1016/j.bioelechem.2016.05.004

16. KLIONSKY DJ et al.Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 2;12(1):1-222.

doi:10.1080/15548627.2015.1100356

17. MARTINS-DUARTE, ÉRICA S. ; CARIAS, MAIRA ; VOMMARO, ROSSIANE ; SUROLIA, NAMITA ; DE SOUZA, WANDERLEY .

Apicoplast fatty acid synthesis is essential for pellicle formation at the end of cytokinesis in Toxoplasma gondii. Journal of Cell Science, v. xx, p.

jcs.185223, 2016.

18. MATADAMAS-MARTÍNEZ, FÉLIX ; CASTILLO, RAFAEL ; HERNÁNDEZ-CAMPOS, ALICIA ; MÉNDEZ-CUESTA, CARLOS ; de Souza,

Wanderley ; GADELHA, ANA PAULA ; NOGUEDA-TORRES, BENJAMÍN ; HERNÁNDEZ, JOSÉ MANUEL ; YÉPEZ-MULIA, LILIÁN .

Proteomic and ultrastructural analysis of the effect of a new nitazoxanide-N-methyl-1H-benzimidazole hybrid against Giardia intestinalis. Research

in Veterinary Science, v. 105, p. 171-179, 2016.

19. MIDLEJ, VICTOR ; PENHA, LUCIANA ; Silva, Rosane ; de Souza, Wanderley ; Benchimol, Marlene . Mitosomal chaperone modulation during

the life cycle of the pathogenic protist Giardia intestinalis. EUROPEAN JOURNAL OF CELL BIOLOGY, v. xx, p. 1-12, 2016.

20. PAREDES-SANTOS, T.C. ; TOMITA, T. ; YAN FEN, M. ; DE SOUZA, W. ; ATTIAS, M. ; VOMMARO, R.C. ; WEISS, L.M. . Development of

dual fluorescent stage specific reporter strain of Toxoplasma gondii to follow tachyzoite and bradyzoite development in vitro and in vivo. Microbes

and Infection, v. 18, p. 39-47, 2016.

21. PINHEIRO, GUILHERME L. ; DE AZEVEDO-MARTINS, ALLAN C. ; Albano, Rodolpho M. ; de Souza, Wanderley ; FRASES, SUSANA .

Comprehensive analysis of the cellulolytic system reveals its potential for deconstruction of lignocellulosic biomass in a novel Streptomyces sp..

Applied Microbiology and Biotechnology, v. xx, p. 1-10, 2016.

22. RITAGLIATI C, VILLANOVA GV, ALONSO VL, ZUMA AA, CRIBB P, MOTTA MC, SERRA EC GLYCOSOMAL BROMO domain factor 1

from Trypanosoma cruzi enhances trypomastigote cell infection and intracellular amastigote growth..Biochem J. 2016 Jan 1;473(1):73-85. doi:

10.1042/BJ20150986.

23. SANT'ANNA, VIVIANE ; DE SOUZA, WANDERLEY ; VOMMARO, ROSSIANE C. . Anthelmintic effect of herbicidal dinitroanilines on the

nematode model Caenorhabditis elegans. Experimental Parasitology, v. 167, p. 43-49, 2016.

24. VIDAL, JULIANA C. ; ALCANTARA, CAROLINA DE L. ; DE SOUZA, WANDERLEY ; CUNHA-E-SILVA, NARCISA L. . Loss of the

cytostome-cytopharynx and endocytic ability are late events in Trypanosoma cruzi metacyclogenesis. JOURNAL OF STRUCTURAL BIOLOGY, v.

xx, p. 1-10, 2016.

25. WENDT C, RACHID R, DE SOUZA W, MIRANDA K. Electron tomography characterization of hemoglobin uptake in Plasmodium chabaudi

reveals a stage-dependent mechanism for food vacuole morphogenesis..J Struct Biol. 2016 Feb 13. pii: S1047-8477(16)30029-6. doi:

10.1016/j.jsb.2016.02.014


http://dx.doi.org/10.3109/08982104.2015.1076462


http://femspd.oxfordjournals.org/content/74/9/ftw108

http://dx.doi.org/10.1016/j.bioelechem.2016.05.004


100

26. ZANETTI, ANDERNICE ; FERREIRA, ROBSON C. ; SERRANO, MYRNA G. ; TAKATA, CARMEN S. ; CAMPANER, MARTA ; ATTIAS,

MARCIA ; de Souza, Wanderley ; TEIXEIRA, MARTA M.G. ; CAMARGO, ERNEY P. . Phytomonas (Euglenozoa: Trypanosomatidae):

phylogenetic analyses support infrageneric lineages and a new species transmitted to Solanaceae fruits by a pentatomid hemipteran. European Journal

of Protistology (Print), 2016. http://dx.doi.org/10.1016/j.ejop.2016.09.004


1. BIANUCCI, RAFAELLA ; TORRES, EDUARDO J LOPES ; SANTIAGO, JULIANA MF DUTRA ; FERREIRA, LUIS F ; NERLICH, ANDREAS

G ; SOUZA, SHEILA MARIA MENDONÇA DE ; GIUFFRA, VALENTINA ; CHIEFFI, PEDRO PAULO ; BASTOS, OTILIO MARIA ;

TRAVASSOS, RENATA ; SOUZA, WANDERLEY DE ; ARAÚJO, ADAUTO Trichuris trichiura in a post-Colonial Brazilian mummy. Memórias

do Instituto Oswaldo Cruz 110, p. 00-00, 2015.doi.org/10.1590/0074-02760140367

2. BORBA-SANTOS LP, GAGINI T, ISHIDA K, DE SOUZA W, ROZENTAL S Miltefosine is active against Sporothrix brasiliensis isolates with in

vitro low susceptibility to amphotericin B or itraconazole.. J Med Microbiol. 2015 Apr;64(Pt 4):415-22. doi: 10.1099/jmm.0.000041. Epub 2015 Feb

13.

3. BRAGA RR, ALMEIDA L, GUERREIRO LH, TINOCO P, MIRANDA KR, BRAGA CA, GADELHA AP, GARCIA S, LIMA LM.J Molecular

confinement of human amylin in lipidic nanoparticles. Liposome Res. 2015 Sep 4:1-11. doi:10.3109/08982104.2015.1076462

4. CATTA-PRETA CM, BRUM FL, DA SILVA CC, ZUMA AA, ELIAS MC, DE SOUZA W, SCHENKMAN S, MOTTA MC Endosymbiosis in

trypanosomatid protozoa: the bacterium division is controlled during the host cell cycle.. Front Microbiol. 2015 Jun2;6:520. doi:

10.3389/fmicb.2015.00520.

5. CHAGAS-MOUTINHO VA, SILVA R, DE SOUZA W, MOTTA MC Identification and ultrastructural characterization of the Wolbachia symbiont

in Litomosoides chagasfilhoi..Parasit Vectors. 2015 Feb 4;8:74. doi: 10.1186/s13071-015-0668-x.

6. DA SILVA LL, PORTES JDE A, DE ARAÚJO MH, SILVA JL, RENNÓ MN, NETTO CD, DA SILVA AJ, COSTA PR, DE SOUZA W, SEABRA

SH, DAMATTA RA Further evidence that naphthoquinone inhibits Toxoplasma gondii growth in vitro..Parasitol Int. 2015 Dec;64(6):622-31. doi:

10.1016/j.parint.2015.08.010.

7. DE ANDRADE ROSA I, DE SOUZA W, BENCHIMOL M Changes in the structural organization of the cytoskeleton of Tritrichomonasfoetus

during trophozoite-pseudocyst transformation..Micron. 2015 Jun;73:28-35. doi: 10.1016/j.micron.2015.03.008.

8. DE AZEVEDO-MARTINS AC, ALVES JM, GARCIA DE MELLO F, VASCONCELOS AT, DE SOUZA W, EINICKER-LAMAS M, MOTTA

MC Biochemical and phylogenetic analyses of phosphatidylinositol production in Angomonasdeanei, an endosymbiont-harboring

trypanosomatid..Parasit Vectors. 2015 Apr 24;8(1):247. doi: 10.1186/s13071-015-0854-x.

9. DE CARVALHO TM, BARRIAS ES, DE SOUZA W. FRONT Macropinocytosis: a pathway to protozoan infection. Physiol. 2015 Apr 9;6:106. doi:

10.3389/fphys.2015.00106. eCollection 2015. Review.

10. DE SOUZA W, ATTIAS M.J New views of the Toxoplasma gondiiparasitophorous vacuole as revealed by Helium Ion Microscopy (HIM). Struct

Biol. 2015 Jul;191(1):76-85. doi: 10.1016/j.jsb.2015.05.003

11. DEMACEDO-SILVA ST, DE SOUZA W, FERNANDES RODRIGUES JC Sterol biosynthesis pathway as an alternative for the anti-protozoan

parasite Chemotherapy.. Curr Med Chem. 2015 Mar 19.

12. GADELHA AP, BENCHIMOL M, DE SOUZA W Helium ion microscopy and ultra-high-resolution scanning electron microscopy analysis of

membrane-extracted cells reveals novel characteristics of the cytoskeleton of Giardia intestinalis.. J Struct Biol. 2015 Jun;190(3):271-8. doi:

10.1016/j.jsb.2015.04.017.

13. GAGLIANO-JUCÁ T, CASTELLI MR, MENDES GD, ARRUDA AM, CHEN LS, DE OLIVEIRA MA, COSTA SF, LOPES AG, DE SOUZA W,

DE NUCCI G Pharmacokinetic and pharmacodynamic evaluation of a nanotechnological topical formulation of lidocaine/prilocaine (nanorap) in

healthy volunteers.TherDrugMonit. 2015 Jun;37(3):362-8. doi: 10.1097/FTD.0000000000000156

14. HENRIQUES C, MILLER MP, CATANHO M, DE CARVALHO TM, KRIEGER MA, PROBST CM, DE SOUZA W, DEGRAVE W, AMARA

SG.Identification and functional characterization of a novel arginine/ornithine transporter, a member of a cationic amino acid transporter subfamily in

the Trypanosoma cruzi genome. ParasitVectors. 2015 Jun25;8:346. doi: 10.1186/s13071-015-0950-y.

15. HERNANDES VV, FRANCO MF, SANTOS JM, MELENDEZ-PEREZ JJ, DE MORAIS DR, ROCHA WF, BORGES R, DE SOUZA W, ZACCA

JJ, LOGRADO LP, EBERLIN MN, CORREA DN Characterization of ANFO explosive by high accuracy ESI(±)-FTMS with forensic identification

on real samples by EASI(-)-MS..ForensicSci Int. 2015 Apr;249:156-64. doi: 10.1016/j.forsciint.2015.01.006.

16. MARTINS-DUARTE ES, DUBAR F, LAWTON P, FRANÇA DA SILVA C, C SOEIRO MDE N, DE SOUZA W, BIOT C, VOMMARO RC

Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.. PLoS One. 2015 May

7;10(5):e0125705. doi: 10.1371/journal.pone.0125705. eCollection 2015.

17. MEDINA JM, RODRIGUES JC, MOREIRA OC, ATELLA G, SOUZA WD, BARRABIN H.Mechanisms of growth inhibition of

Phytomonasserpens by the alkaloids tomatine and tomatidine. Mem Inst Oswaldo Cruz. 2015 Feb;110(1):48-55. doi: 10.1590/0074-02760140097.

18. MIRANDA K, GIRARD-DIAS W, ATTIAS M, DE SOUZA W, RAMOS I.Three dimensional reconstruction by electron microscopy in the life

sciences: An introduction for cell and tissue biologists. Mol Reprod Dev. 2015 Feb 4. doi: 10.1002/mrd.22455.

19. MIRANDA, FARLEN JOSÉ BEBBER ; SOUZA, DIOGO BENCHIMOL DE ; FRAZÃO-TEIXEIRA, EDWARDS ; OLIVEIRA, FÁBIO

CONCEIÇÃO DE ; MELO, JOÃO CARDOSO DE ; MARIANO, CARLOS MAGNO ANSELMO ; ALBERNAZ, ANTONIO PEIXOTO ;

CARVALHO, EULÓGIO CARLOS QUEIRÓZ DE ; OLIVEIRA, FRANCISCO CARLOS RODRIGUES DE ; SOUZA, WANDERLEY DE ;

DAMATTA, RENATO AUGUSTO Experimental infection with the Toxoplasma gondii ME-49 strain in the Brazilian BR-1 mini pig is a suitable

animal model for human toxoplasmosis. Memórias do Instituto Oswaldo Cruz 110 (1) 2015 doi.org/10.1590/0074-02760140318

20. MIRIA GOMES PEREIRA, GONZALO VISBAL, LEONARDO T. SALGADO, JULIANA CUNHA VIDAL, JOSEANE L. P. GODINHO,

NUCCIA N. T. DE CICCO, GEÓRGIA C. ATELLA,WANDERLEY DE SOUZA, NARCISA CUNHA-E-SILVA Trypanosoma cruzi Epimastigotes

Are Able to Manage Internal Cholesterol Levels under Nutritional Lipid Stress Conditions.. PLoS One. 2015 Jun 11;10(6):e0128949.

doi:10.1371/journal.pone.0128949.

21. MOR V, RELLA A, FARNOUD AM, SINGH A, MUNSHI M, BRYAN A, NASEEM S, KONOPKA JB, OJIMA I, BULLESBACH E,

ASHBAUGH A, LINKE MJ, CUSHION M, COLLINS M, ANANTHULA HK, SALLANS L, DESAI PB, WIEDERHOLD NP, FOTHERGILL

AW, KIRKPATRICK WR, PATTERSON T, WONG LH, SINHA S, GIAEVER G, NISLOW C, FLAHERTY P, PAN X, CESAR GV, DE MELO

TAVARES P, FRASES S, MIRANDA K, RODRIGUES ML, LUBERTO C, NIMRICHTER L, DEL POETA M. Identification of a New Class of

Antifungals Targeting the Synthesis of Fungal Sphingolipids..MBio. 2015 Jun 23;6(3):e00647. doi: 10.1128/mBio.00647-15

22. MOREIRA-SOUZA AC, MARINHO Y, CORREA G, SANTORO GF, COUTINHO CM, VOMMARO RC, COUTINHO-SILVA R Pyrimidinergic

Receptor Activation Controls Toxoplasma gondii Infection in Macrophages..PLoSOne. 2015 Jul 20;10(7):e0133502. doi:

10.1371/journal.pone.0133502. eCollection 2015.

23. NICO D, MARAN N, SANTOS L, RAMOS-JUNIOR ES, MANTUANO NR, COUTINHO JL, VALE AM, FREIRE-DE-LIMA CG, TODESCHINI

A, RODRIGUES JC, PALATNIK-DE-SOUSA CB, MORROT A.Expression of leukosialin (CD43) defines a major intrahepatic T cell subset

associated with protective responses in visceral leishmaniasis. ParasitVectors. 2015 Feb 19;8:111. doi: 10.1186/s13071-015-0721-9.

24. NIYOGI S, JIMENEZ V, GIRARD-DIAS W, DE SOUZA W, MIRANDA K, DOCAMPO R Rab32 is essential for maintaining functional

acidocalcisomes and for growth and infectivity of Trypanosoma cruzi.. J Cell Sci. 2015 May 11. pii: jcs.169466.

25. PINHEIRO GL, CORREA RF, CUNHA RS, CARDOSO AM, CHAIA C, CLEMENTINO MM, GARCIA ES, DE SOUZA W, FRASÉS S Isolation

of aerobic cultivable cellulolytic bacteria from different regions of the gastrointestinal tract of giant land snail Achatina fulica.. Front Microbiol. 2015

Aug20;6:860. doi: 10.3389/fmicb.2015.00860. eCollection 2015.

26. SUHETT GD, DE SOUZA SA, CARVALHO AB, RACHID RP, DA CUNHA-E-SILVA NL, DE CARVALHO AC, DA FONSECA LM,

GOLDENBERG RC, GUTFILEN B 99m-Technetium binding site in bone marrow mononuclear cells..StemCell Res Ther. 2015 Jun 4;6(1):115.

27. TELES CB, MOREIRA-DILL LS, SILVA ADE A, FACUNDO VA, DE AZEVEDO WF JR, DA SILVA LH, MOTTA MC, STÁBELI RG, SILVA-

JARDIM I.BMC A lupane-triterpene isolated from Combretum leprosum Mart. fruit extracts that interferes with the intracellular development of

Leishmania (L.) amazonensis in vitro. ComplementAltern Med. 2015 Jun6;15:165. doi: 10.1186/s12906-015-0681-9.

http://dx.doi.org/10.1016/j.ejop.2016.09.004


101

28. VARGAS G, ROCHA JD, OLIVEIRA DL, ALBUQUERQUE PC, FRASES S, SANTOS SS, NOSANCHUK JD, GOMES AM, MEDEIROS LC,

MIRANDA K, SOBREIRA TJ, NAKAYASU ES, ARIGI EA, CASADEVALL A, GUIMARAES AJ, RODRIGUES ML, FREIRE-DE-LIMA CG,

ALMEIDA IC, NIMRICHTER L.Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans. Cell

Microbiol. 2015 Mar;17(3):389-407. doi: 10.1111/cmi.12374.

29. VEIGA-SANTOS P, LI K, LAMEIRA L, DE CARVALHO TM, HUANG G, GALIZZI M, SHANG N, LI Q, GONZALEZ-PACANOWSKA D,

HERNANDEZ-RODRIGUEZ V, BENAIM G, GUO RT, URBINA JA, DOCAMPO R, DE SOUZA W, OLDFIELD E..SQ109, a new drug lead for

Chagas disease. Antimicrob Agents Chemother. 2015 Apr;59(4):1950-61. doi: 10.1128/AAC.03972-14.

30. XIMENES AD, SILVA-CARDOSO L, DE CICCO NN, PEREIRA MG, LOURENÇO DC, FAMPA P, FOLLY E, CUNHA-E-SILVA NL, SILVA-

NETO MA, ATELLA GC.Lipophorin Drives Lipid Incorporation and Metabolism in Insect Trypanosomatids. Protist. 2015 Apr 17;166(3):297-309.

doi: 10.1016/j.protis.2015.04.003.

31. ZUMA AA, CAVALCANTI DP, ZOGOVICH M, MACHADO AC, MENDES IC, THIRY M, GALINA A, DE SOUZA W, MACHADO CR,

MOTTA MC Unveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and

replication..Parasitol Res. 2015 Feb;114(2):419-30. doi: 10.1007/s00436-014-4199-8.


1. ADADE CM, CARVALHO AL, TOMAZ MA, COSTA TF, GODINHO JL, MELO PA, LIMA AP, RODRIGUES JC, ZINGALI RB, SOUTO-

PADRÓN T.Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against Trypanosomes and Leishmania.

PLoSNeglTropDis. 2014 Oct 16;8(10):e3252. 10.1371/journal.pntd.0003252

2. ALBUQUERQUE PC, FONSECA FL, DUTRA FF, BOZZA MT, FRASES S, CASADEVALL A, RODRIGUES ML Cryptococcus neoformans

glucuronoxylomannan fractions of different molecular masses are functionally distinct.. Future Microbiol. 2014 Feb;9(2):147-61.

10.2217/fmb.13.163.

3. ALCANTARA CL, VIDAL JC, DE SOUZA W, CUNHA-E-SILVA NL. The three-dimensional structure of the cytostome-cytopharynx complex of

Trypanosoma cruzi epimastigotes. J Cell Sci. 2014 May 15;127(Pt 10):2227-37 10.1242/jcs.135491.

4. AZEVEDO-MARTINS AC, MACHADO AC, KLEIN CC, CIAPINA L, GONZAGA L, VASCONCELOS AT, SAGOT MF, DE SOUZA W,

EINICKER-LAMAS M, GALINA A, MOTTA MC Mitochondrial respiration and genomic analysis provide insight into the influence of the

symbiotic bacterium on host trypanosomatid oxygen consumption.. Parasitology. 2014 Aug 27:1-11.10.1017/S0031182014001139

5. BENCHIMOL M, ENGEL JC, TAN KS, DE SOUZA W. Cell biology of pathogenic protozoa and their interaction with host cells. Biomed Res

Int. 2014;2014:143418 10.1155/2014/143418

6. BRUM FL, CATTA-PRETA CM, DE SOUZA W, SCHENKMAN S, ELIAS MC, MOTTA MC. Structural characterization of the cell division cycle

in Strigomonas culicis, an endosymbiont-bearing trypanosomatid. Microsc Microanal. 2014 Feb;20(1):228-37.

10.1017/S1431927613013925.

7. COELHO-SOUZA T, MARTINS N, MAIA F, FRASES S, BONELLI RR, RILEY LW, MOREIRA BM. Pyomelanin production: a rare phenotype

in Acinetobacter baumannii. J Med Microbiol. 2014 Jan;63(Pt 1):152-4. 10.1099/jmm.0.064089-0

8. CRUZ KD, CRUZ TA, VERAS DE MORAES G, PAREDES-SANTOS TC, ATTIAS M, DE SOUZA W.Disruption of lipid rafts interferes with the

interaction of Toxoplasma gondii with macrophages and epithelial cells. Biomed Res Int. 2014;2014:687835. 10.1155/2014/687835

9. DE MACEDO-SILVA ST, URBINA JA, DE SOUZA W, RODRIGUES JC. In vitro activity of the antifungal azoles itraconazole and posaconazole

against Leishmania amazonensis. PLoS One. 2013 Dec 23;8(12):e83247. 10.1371/journal.pone.0083247

10. DE SOUZA W Trypanosoma cruzi-Host Cell Interaction.. Front Immunol. 2014 Aug 4;5:339. doi: 10.3389/fimmu.2014.00339

11. DIAS FDE A, VASCONCELLOS LR, ROMEIRO A, ATTIAS M, SOUTO-PADRÓN TC, LOPES AH.Transovum transmission of trypanosomatid

cysts in the Milkweed bug, Oncopeltus fasciatus. PLoSOne. 2014 Sep 26;9(9):e108746. doi: 10.1371/journal.pone.0108746

12. FONSECA-DE-SOUZA AL, FREITAS-MESQUITA AL, VIEIRA LP, MAJEROWICZ D, DAFLON-YUNES N, SOARES-DE-MEDEIROS LC,

MIRANDA K, GONDIM KC, MEYER-FERNANDES JR.Identification and characterization of an ecto-pyrophosphatase activity in intact

epimastigotes of Trypanosoma rangeli. PLoSOne. 2014 Sep 9;9(9):e106852. doi: 10.1371/journal.pone.0106852

13. GARCIA-SILVA MR, CABRERA-CABRERA F, DAS NEVES RF, SOUTO-PADRÓN T, DE SOUZA W, CAYOTA A. Gene expression changes

induced by Trypanosoma cruzi shed microvesicles in mammalian host cells: relevance of tRNA-derived halves. Biomed Res Int.

2014;2014:305239. 10.1155/2014/305239

14. GARCIA-SILVA MR, DAS NEVES RF, CABRERA-CABRERA F, SANGUINETTI J, MEDEIROS LC, ROBELLO C, NAYA H, FERNANDEZ-

CALERO T, SOUTO-PADRON T, DE SOUZA W, CAYOTA A. Extracellular vesicles shed by Trypanosoma cruzi are linked to small RNA

pathways, life cycle regulation, and susceptibility to infection of mammalian cells. Parasitol Res. 2014 Jan;113(1):285-304. 10.1007/s00436-013-

3655-1

15. GODINHO RM, CRESTANI J, KMETZSCH L, ARAUJO GDE S, FRASES S, STAATS CC, SCHRANK A, VAINSTEIN MH, RODRIGUES ML

The vacuolar-sorting protein Snf7 is required for export of virulence determinants in members of the Cryptococcus neoformans complex..Sci Rep.

2014 Sep 2;4:6198. doi: 10.1038/srep06198.

16. GUERRA CR, SEABRA SH, DE SOUZA W, ROZENTAL S.Cryptococcus neoformans is internalized by receptor-mediated or 'triggered'

phagocytosis, dependent on actin recruitment. PLoSOne. 2014 21;9(2):e89250.10.1371/journal.pone.0089250.

17. HENRIQUES C, HENRIQUES-PONS A, MEUSER-BATISTA M, RIBEIRO AS, DE SOUZA W In vivo imaging of mice infected with

bioluminescent Trypanosoma cruzi unveils novel sites of infection. Paras. Vectors. 2014 Mar 3;7:89 10.1186/1756-3305-7-89.

18. INOUE AH, SERPELONI M, HIRAIWA PM, YAMADA-OGATTA SF, MUNIZ JR, MOTTA MC, VIDAL NM, GOLDENBERG S, AVILA AR

Identification of a novel nucleocytoplasmic shuttling RNA helicase of trypanosomes..PLoSOne. 2014 Oct 14;9(10):e109521. doi:

10.1371/journal.pone.0109521

19. ISHIDA K, CIPRIANO TF, ROCHA GM, WEISSMÜLLER G, GOMES F, MIRANDA K, ROZENTAL S. Silver nanoparticle production by the

fungus Fusarium oxysporum: nanoparticle characterisation and analysis of antifungal activity against pathogenic yeasts. Mem Inst Oswaldo Cruz.

2014 Apr;109(2):220-8

20. LACOMBE OK, ZUMA AA, DA SILVA CC, DE SOUZA W, MOTTA MC. Effects of camptothecin derivatives and topoisomerase dual inhibitors

on Trypanosoma cruzi growth and ultrastructure. J Negat Results Biomed. 2014 Jun 10;13(1):11. 10.1186/1477-5751-13-11.

21. PARK YD, SHIN S, PANEPINTO J, RAMOS J, QIU J, FRASES S, ALBUQUERQUE P, CORDERO RJ, ZHANG N, HIMMELREICH U,

BEENHOUWER D, BENNETT JE, CASADEVALL A, WILLIAMSON PR A role for LHC1 in higher order structure and complement binding of

the Cryptococcus neoformans capsule.. PLoSPathog. 2014 May 1;10(5):e1004037. 10.1371/journal.ppat.1004037

22. PETROPOLIS DB, RODRIGUES JC, VIANA NB, PONTES B, PEREIRA CF, SILVA-FILHO FC. Leishmania amazonensis promastigotes in 3D

Collagen I culture: an in vitro physiological environment for the study of extracellular matrix and host cell interactions. PeerJ. 2014 Apr 3;2:e317.

10.7717/peerj.317

23. PISSINATE K, DOS SANTOS MARTINS-DUARTE É, SCHAFFAZICK SR, DE OLIVEIRA CP, VOMMARO RC, GUTERRES SS,

POHLMANN AR, DE SOUZA W. Pyrimethamine-loaded lipid-core nanocapsules to improve drug efficacy for the treatment of toxoplasmosis.

Parasitol Res. 2014 Feb;113(2):555-64. doi: 10.1007/s00436-013-3715-6.

24. RAJÃO MA, FURTADO C, ALVES CL, PASSOS-SILVA DG, DE MOURA MB, SCHAMBER-REIS BL, KUNRATH-LIMA M, ZUMA AA,

VIEIRA-DA-ROCHA JP, GARCIA JB, MENDES IC, PENA SD, MACEDO AM, FRANCO GR, DE SOUZA-PINTO NC, DE MEDEIROS MH,

CRUZ AK, MOTTA MC, TEIXEIRA SM, MACHADO CR. Unveiling benznidazole's mechanism of action through overexpression of DNA repair

proteins in Trypanosoma cruzi. Environ Mol Mutagen. 2014 May;55(4):309-21. 10.1002/em.21839.

25. RAMOS PK, BRITO MDE V, SILVEIRA FT, SALGADO CG, DE SOUZA W, PICANÇO-DINIZ CW, PICANÇO-DINIZ JA In vitro cytokines

profile and ultrastructural changes of microglia and macrophages following interaction with Leishmania..Parasitology. 2014 Jul;141(8):1052-63.

10.1017/S0031182014000274


102

26. REIGNAULT LC, BARRIAS ES, SOARES MEDEIROS LC, DE SOUZA W, DE CARVALHO TM. Structures containing galectin-3 are recruited

to the parasitophorous vacuole containing Trypanosoma cruzi in mouse peritoneal macrophages. Parasitol Res. 2014 Jun;113(6):2323-33.

10.1007/s00436-014-3887-8

27. RIZZO J, OLIVEIRA DL, JOFFE LS, HU G, GAZOS-LOPES F, FONSECA FL, ALMEIDA IC, FRASES S, KRONSTAD JW, RODRIGUES ML.

Role of the Apt1 protein in polysaccharide secretion by Cryptococcus neoformans. Eukaryot Cell. 2014 Jun;13(6):715-26 10.1128/EC.00273-13

28. ROCHA DA, DE ANDRADE ROSA I, DE SOUZA W, BENCHIMOL M. Evaluation of the effect of miltefosine on Trichomonas vaginalis.

Parasitol Res. 2014 Mar;113(3):1041-7 10.1007/s00436-013-3738-z

29. ROCHA DA, DE ANDRADE ROSA I, URBINA JA, DE SOUZA W, BENCHIMOL M. The effect of 3-(biphenyl-4-yl)-3-hydoxyquinuclidine

(BPQ-OH) and metronidazole on Trichomonas vaginalis: a comparative study. Parasitol Res. 2014 Jun;113(6):2185-97. 10.1007/s00436-014-

3871-3

30. RODRIGUES JC, GODINHO JL, DE SOUZA W Biology of human pathogenic trypanosomatids: epidemiology, lifecycle and ultrastructure..

Subcell Biochem. 2014;74:1-42 10.1007/978-94-007-7305-9_1

31. SANTOS JR, HOLANDA RA, FRASES S, BRAVIM M, ARAUJO G DE S, SANTOS PC, COSTA MC, RIBEIRO MJ, FERREIRA GF,

BALTAZAR LM, MIRANDA AS, OLIVEIRA DB, SANTOS CM, FONTES AC, GOUVEIA LF, RESENDE-STOIANOFF MA, ABRAHÃO JS,

TEIXEIRA AL, PAIXÃO TA, SOUZA DG, SANTOS DAFluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct

behaviors in murine Cryptococcosis..PLoSOne. 2014 Nov 13;9(11):e112669. 10.1371/journal.pone.0112669

32. SCHMIDT EM, FRANCO MF, REGINO KG, LEHMANN EL, ARRUDA MA, DE CARVALHO ROCHA WF, BORGES R, DE SOUZA W,

EBERLIN MN, CORREA DN.Direct and non-destructive proof of authenticity for the 2nd generation of Brazilian real banknotes via easy ambient

sonic spray ionization mass spectrometry. Sci Justice. 2014 Dec;54(6):459-64. 10.1016/j.scijus.2014.08.001

33. SHANG N, LI Q, KO TP, CHAN HC, LI J, ZHENG Y, HUANG CH, REN F, CHEN CC, ZHU Z, GALIZZI M, LI ZH, RODRIGUES-POVEDA

CA, GONZALEZ-PACANOWSKA D, VEIGA-SANTOS P, DE CARVALHO TM, DE SOUZA W, URBINA JA, WANG AH, DOCAMPO R, LI

K, LIU YL, OLDFIELD E, GUO RT. Squalene synthase as a target for Chagas disease therapeutics. PLoS Pathog. 2014 May 1;10(5):e1004114.

10.1371/journal.ppat.1004114

34. SOUZA-FERREIRA PS, MANSUR JF, BERNI M, MOREIRA MF, DOS SANTOS RE, ARAÚJO HM, DE SOUZA W, RAMOS IB, MASUDA

H.Chitin deposition on the embryonic cuticle of Rhodnius prolixus: The reduction of CHS transcripts by CHS-dsRNA injection in females affects

chitin deposition and eclosion of the first instar nymph. InsectBiochem Mol Biol. 2014 Aug;51:101-9. 10.1016/j.ibmb.2013.12.004

35. ULRICH PN, LANDER N, KURUP SP, REISS L, BREWER J, SOARES MEDEIROS LC, MIRANDA K, DOCAMPO R The acidocalcisome

vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi.

J Eukaryot Microbiol. 2014 Mar-Apr;61(2):155-65. 10.1111/jeu.12093.

36. VEIGA-SANTOS P, REIGNAULT LC, HUBER K, BRACHER F, DE SOUZA W, DE CARVALHO TM Inhibition of NAD+-dependent histone

deacetylases (sirtuins) causes growth arrest and activates both apoptosis and autophagy in the pathogenic protozoan Trypanosoma cruzi. Parasitology.

2014 May;141(6):814-25. 10.1017/S0031182013001704

37. ZUMA AA, MENDES IC, REIGNAULT LC, ELIAS MC, DE SOUZA W, MACHADO CR, MOTTA MC. How Trypanosoma cruzi handles cell

cycle arrest promoted by camptothecin, a topoisomerase I inhibitor. Mol Biochem Parasitol. 2014 Feb;193(2):93-100.

10.1016/j.molbiopara.2014.02.001


1. ADNET FA, GONÇALVES JP, DE SOUZA W, ATTIAS M. A simple and efficient method to observe internal structures of helminths by scanning

electron microscopy. Microsc Microanal. 2013 Dec;19(6):1470-4. 10.1017/S1431927613013706

2. ALVES JM, KLEIN CC, DA SILVA FM, COSTA-MARTINS AG, SERRANO MG, BUCK GA, VASCONCELOS AT, SAGOT MF, TEIXEIRA

MM, MOTTA MC, CAMARGO EP Endosymbiosis in trypanosomatids: the genomic cooperation between bacterium and host in the synthesis of

essential amino acids is heavily influenced by multiple horizontal gene transfers.. BMC Evol Biol. 2013 Sep 9;13:190. 10.1186/1471-2148-13-190.

3. BARRIAS ES, DE CARVALHO TM, DE SOUZA W. Trypanosoma cruzi: Entry into Mammalian Host Cells and Parasitophorous Vacuole

Formation. Front Immunol. 2013 Aug1;4:186. 10.3389/fimmu.2013.00186

4. BAYER-SANTOS E, CUNHA-E-SILVA NL, YOSHIDA N, FRANCO DA SILVEIRA Expression and cellular trafficking of GP82 and GP90

glycoproteins during Trypanosoma cruzi metacyclogenesis. J. Parasites & Vectors. 2013 May 1;6:127.10.1186/1756-3305-6-127

5. BERTINO-GRIMALDI D, MEDEIROS MN, VIEIRA RP, CARDOSO AM, TURQUE AS, SILVEIRA CB, ALBANO RM, BRESSAN-

NASCIMENTO S, GARCIA ES, DE SOUZA W, MARTINS OB, MACHADO EA. Bacterial community composition shifts in the gut of Periplaneta

americana fed on different lignocellulosic materials. Springerplus. 2013 Nov 15;2:60910.1186/2193-1801-2-609

6. BUTLER CE, DE CARVALHO TM, GRISARD EC, FIELD RA, TYLER KM. Trans-sialidase stimulates eat me response from epithelial cells.

Traffic. 2013 Jul;14(7):853-69. 10.1111/tra.12078

7. CALDAS LA, SEABRA SH, ATTIAS M, DE SOUZA W. The effect of kinase, actin, myosin and dynamin inhibitors on host cell egress by

Toxoplasma gondii. Parasitol Int. 2013 Oct;62(5):475-82. 10.1016/j.parint.2013.04.006

8. CASTRO RA, KUBITSCHEK-BARREIRA PH, TEIXEIRA PA, SANCHES GF, TEIXEIRA MM, QUINTELLA LP, ALMEIDA SR, COSTA RO,

CAMARGO ZP, FELIPE MS, DE SOUZA W, LOPES-BEZERRA LM Differences in cell morphometry, cell wall topography and gp70 expression

correlate with the virulence of Sporothrix brasiliensis clinical isolates. PLoS One. 2013 Oct 7;8(10):e75656. 10.1371/journal.pone.0075656

9. CHAGAS-MOUTINHO VA, SANT'ANNA V, OLIVEIRA-MENEZES A, DE SOUZA W. New Aspidoderidae species parasite of Didelphis aurita

(Mammalia: Didelphidae): A light and scanning electron microscopy approach. Acta Trop. 2013 Oct 12. pii: S0001-706X(13)00279-9.

10.1016/j.actatropica.2013.10.005

10. CORDERO RJ, PONTES B, FRASES S, NAKOUZI AS, NIMRICHTER L, RODRIGUES ML, VIANA NB, CASADEVALL A. Antibody binding

to Cryptococcus neoformans impairs budding by altering capsular mechanical properties. J Immunol. 2013 Jan 1;190(1):317-23

10.4049/jimmunol.1202324

11. DE ANDRADE ROSA I, DE SOUZA W, BENCHIMOL M. High-resolution scanning electron microscopy of the cytoskeleton of

Tritrichomonasfoetus. J Struct Biol. 2013 Sep;183(3):412-8. 10.1016/j.jsb.2013.07.002

12. DE B MOREIRA TL, BARBOSA AF, VEIGA-SANTOS P, HENRIQUES C, HENRIQUES-PONS A, GALDINO SL, DE LIMA M DO C, PITTA

IDA R, DE SOUZA W, DE CARVALHO TM Effect of thiazolidine LPSF SF29 on the growth and morphology of Trypanosoma cruzi. Int J

Antimicrob Agents. 2013 Feb;41(2):183-7 10.1016/j.ijantimicag.2012.09.018

13. DE SOUZA W, DE CARVALHO TM. Active penetration of Trypanosoma cruzi into host cells: historical considerations and current concepts. Front

Immunol. 2013 Jan 25;4:2. 10.3389/fimmu.2013.00002.

14. EUGENIN EA, GRECO JM, FRASES S, NOSANCHUK JD, MARTINEZ LR.Methamphetamine alters blood brain barrier protein expression in

mice, facilitating central nervous system infection by neurotropic Cryptococcus neoformans. J Infect Dis. 2013;208(4):699-704.

10.1093/infdis/jit117.

15. FONSECA FL, GUIMARÃES AJ, KMETZSCH L, DUTRA FF, SILVA FD, TABORDA CP, ARAUJO GDE S, FRASES S, STAATS CC, BOZZA

MT, SCHRANK A, VAINSTEIN MH, NIMRICHTER L, CASADEVALL A, RODRIGUES ML. Binding of the wheat germ lectin to Cryptococcus

neoformans chitooligomers affects multiple mechanisms required for fungal pathogenesis. Fungal Genet Biol. 2013 Nov;60:64-73.

10.1016/j.fgb.2013.04.005.

16. GADELHA AP, CUNHA-E-SILVA NL, DE SOUZA W. Assembly of the Leishmania amazonensis flagellum during cell differentiation. J Struct

Biol. 2013Nov;184(2):280-92. 10.1016/j.jsb.2013.09.006

17. GALIZZI M, BUSTAMANTE JM, FANG J, MIRANDA K, SOARES MEDEIROS LC, TARLETON RL, DOCAMPO R. Evidence for the role of

vacuolar soluble pyrophosphatase and inorganic polyphosphate in Trypanosoma cruzi persistence. Mol Microbiol. 2013 Nov;90(4):699-

715. 10.1111/mmi.12392


103

18. GODINHO JL, GEORGIKOPOULOU K, CALOGEROPOULOU T, DE SOUZA W, RODRIGUES JC. A novel alkyl phosphocholine-dinitroaniline

hybrid molecule exhibits biological activity in vitro against Leishmaniaamazonensis. ExpParasitol. 2013Sep;135(1):153-65.

10.1016/j.exppara.2013.06.015

19. GOMES FM, RAMOS IB, WENDT C, GIRARD-DIAS W, DE SOUZA W, MACHADO EA, MIRANDA K. New insights into the in situ

microscopic visualization and quantification of inorganic polyphosphate stores by 4',6-diamidino-2-phenylindole (DAPI)-staining Eur J

Histochem. 2013 5;57(4):e3410.4081/ejh.2013.e34

20. GONÇALVES JP, OLIVEIRA-MENEZES A, MALDONADO JUNIOR A, CARVALHO TM, DE SOUZA W.Evaluation of praziquantel effects on

Echinostoma paraensei ultrastructure. Vet Parasitol. 2013 May 1;194(1):16-25. 10.1016/j.vetpar.2012.12.042

21. GRIECO MA, CAVALCANTE JJ, CARDOSO AM, VIEIRA RP, MACHADO EA, CLEMENTINO MM, MEDEIROS MN, ALBANO RM,

GARCIA ES, DE SOUZA W, CONSTANTINO R, MARTINS OB. Microbial community diversity in the gut of the South American termite

Cornitermes cumulans (Isoptera: Termitidae). Microb Ecol. 2013 Jan;65(1):197-204 10.1007/s00248-012-0119-6

22. KLEIN CC, ALVES JM, SERRANO MG, BUCK GA, VASCONCELOS AT, SAGOT MF, TEIXEIRA MM, CAMARGO EP, MOTTA MC

Biosynthesis of vitamins and cofactors in bacterium-harbouring trypanosomatids depends on the symbiotic association as revealed by genomic

analyses. .PLoS One. 2013 Nov 19;8(11):e79786. 10.1371/journal.pone.0079786

23. LIMA L, ESPINOSA-ÁLVAREZ O, HAMILTON PB, NEVES L, TAKATA CS, CAMPANER M, ATTIAS M, DE SOUZA W, CAMARGO EP,

TEIXEIRA MM. Trypanosoma livingstonei: a new species from African bats supports the bat seeding hypothesis for the Trypanosoma cruzi clade.

Parasit Vectors. 2013 Aug 3;6(1):221. 10.1186/1756-3305-6-221

24. LOPES TORRES EJ, DE SOUZA W, MIRANDA K. Comparative analysis of Trichuris muris surface using conventional, low vacuum,

environmental and field emission scanning electron microscopy. Vet Parasitol. 2013 Sep 23;196(3-4):409-16. 10.1016/j.vetpar.2013.02.026

25. LUCENA SA, MORAES CS, COSTA SG, DE SOUZA W, AZAMBUJA P, GARCIA ES, GENTA FA. Miniaturization of hydrolase assays in

thermocyclers. Anal Biochem. 2013 Mar 1;434(1):39-43. 10.1016/j.ab.2012.10.032

26. MAIA-BRIGAGÃO C, GADELHA AP, DE SOUZA W. New associated structures of the anterior flagella of Giardia duodenalis. Microsc Microanal.

2013 Oct;19(5):1374-6 10.1017/S1431927613013275

27. MANCHESTER T, CAVALCANTI DP, ZOGOVICH M, DE SOUZA W, MOTTA MC. Acriflavine treatment promotes dyskinetoplasty in

Trypanosoma cruzi as revealed by ultrastructural analysis. Parasitology. 2013 Sep;140(11):1422-31. 10.1017/S0031182013001029

28. MARTINS-DUARTE ÉS, DE SOUZA W, VOMMARO RC. Toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and

pyrimethamine against acute toxoplasmosis in murine model. Exp Parasitol. 2013 Mar;133(3):294-9.10.1016/j.exppara.2012.12.011

29. MOTTA MC, MARTINS AC, DE SOUZA SS, CATTA-PRETA CM, SILVA R, KLEIN CC, DE ALMEIDA LG, DE LIMA CUNHA O, CIAPINA

LP, BROCCHI M, COLABARDINI AC, DE ARAUJO LIMA B, MACHADO CR, DE ALMEIDA SOARES CM, PROBST CM, DE MENEZES

CB, THOMPSON CE, BARTHOLOMEU DC, GRADIA DF, PAVONI DP, GRISARD EC, FANTINATTI-GARBOGGINI F, MARCHINI FK,

RODRIGUES-LUIZ GF, WAGNER G, GOLDMAN GH, FIETTO JL, ELIAS MC, GOLDMAN MH, SAGOT MF, PEREIRA M, STOCO PH, DE

MENDONÇA-NETO RP, TEIXEIRA SM, MACIEL TE, DE OLIVEIRA MENDES TA, ÜRMÉNYI TP, DE SOUZA W, SCHENKMAN S, DE

VASCONCELOS AT. Predicting the proteins of Angomonas deanei, Strigomonas culicis and their respective endosymbionts reveals new aspects of

the trypanosomatidae family. PLoSOne. 2013;8(4):e60209. 10.1371/journal.pone.0060209

30. OLIVEIRA DM, GOMES FM, CARVALHO DB, RAMOS I, CARNEIRO AB, SILVA-NETO MA, DE SOUZA W, LIMA AP, MIRANDA K,

MACHADO EA. Yolk hydrolases in the eggs of Anticarsia gemmatalis hubner (Lepidoptera: Noctuidae): a role for inorganic polyphosphate towards

yolk mobilization. J InsectPhysiol. 2013 Dec;59(12):1242-9. 10.1016/j.jinsphys.2013.09.008

31. ORSINGER-JACOBSEN SJ, PATEL SS, VELLOZZI EM, GIALANELLA P, NIMRICHTER L, MIRANDA K, MARTINEZ LR. Use of a stainless

steel washer platform to study Acinetobacter baumannii adhesion and biofilm formation on abiotic surfaces. Microbiology. 2013 Dec;159(Pt

12):2594-604. 10.1099/mic.0.068825-0

32. PAREDES-SANTOS TC, MARTINS-DUARTE ES, VITOR RW, DE SOUZA W, ATTIAS M, VOMMARO RC. Spontaneous cystogenesis in vitro

of a Brazilian strain of Toxoplasma gondii. Parasitol Int. 2013 Apr;62(2):181-8 10.1016/j.parint.2012.12.003

33. PATEL D, DESAI GM, FRASES S, CORDERO RJ, DELEON-RODRIGUEZ CM, EUGENIN EA, NOSANCHUK JD, MARTINEZ LR.

Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain. MBio. 2013 Jul 30;4(4). pii: e00400-

13. 10.1128/mBio.00400-13.

34. PAUER H, CAVALCANTI SN, TEIXEIRA FL, SANTOS-FILHO J, VOMMARO RC, OLIVEIRA AC, FERREIRA EO, DOMINGUES RR.

Inactivation of a fibronectin-binding TonB-dependent protein increases adhesion properties of Bacteroides fragilis. J Med Microbiol. 2013

;62(Pt 10):1524-30. 10.1099/jmm.0.054692-0

35. PISSINATE K, DOS SANTOS MARTINS-DUARTE E, SCHAFFAZICK SR, DE OLIVEIRA CP, VOMMARO RC, GUTERRES SS,

POHLMANN AR, DE SOUZA W. Pyrimethamine-loaded lipid-core nanocapsules to improve drug efficacy for the treatment of toxoplasmosis

Parasitol Res. 2013 Nov 29.

36. ROCHA DA, DE ANDRADE ROSA I, DE SOUZA W, BENCHIMOL M. Evaluation of the effect of miltefosine on Trichomonas vaginalis.

Parasitol Res. 2013

37. RODRIGUES ML, FRANZEN AJ, NIMRICHTER L, MIRANDA K.Vesicular mechanisms of traffic of fungal molecules to the extracellular space.

Curr Opin Microbiol. 2013 Aug;16(4):414-20. 10.1016/j.mib.2013.04.002

38. SANT'ANNA C, COSTA LT, ABUD Y, BIANCATTO L, MIGUENS FC, DE SOUZA W. Sugarcane cell wall structure and lignin distribution

investigated by confocal and electron microscopy. Microsc Res Tech. 2013 Aug;76(8):829-34. 10.1002/jemt.22235

39. SANT'ANNA V, VOMMARO RC, DE SOUZA W. Caenorhabditis elegans as a model for the screening of anthelminthic compounds: ultrastructural

study of the effects of albendazole. ExpParasitol. 2013 Sep;135(1):1-8. 10.1016/j.exppara.2013.05.011

40. TEIXEIRA DE, BENCHIMOL M, RODRIGUES JC, CREPALDI PH, PIMENTA PF, DE SOUZA W The cell biology of Leishmania: how to teach

using animations. PLoS Pathog.2013;9(10):e1003594. 10.1371/journal.ppat.1003594

41. VILA TV, ISHIDA K, DE SOUZA W, PROUSIS K, CALOGEROPOULOU T, ROZENTAL S.Effect of alkylphospholipids on Candida albicans

biofilm formation and maturation. J Antimicrob Chemother. 2013 Jan;68(1):113-25. 10.1093/jac/dks353


104

AL 10 - Associated Laboratory of Genomic, Proteomic,

Modeling and Nanoscopy of Biological Systems

- Coodinator:

Paulo Mascarello Bisch - Instituto de Biofísica Carlos Chagas Filho (IBCCF/UFRJ)

- Researchers from national institutions: Ana Beatriz Furlanetto Pacheco –IBCCF/UFRJ

Gilberto Weissmuller – IBCCF/UFRJ

Wanda Maria Almeida von Kruger –IBCCF/UFRJ


Carolina Lage Goulart (UFRJ)

Gustavo Miranda Rocha (UFRJ)

Livia de Carvalho Barbosa (UFRJ)


Allan Amorim Santos (UFRJ)

Daniel Moreira da Costa Leite (UFRJ)

Iamê Alves Guedes (UFRJ)

Leandro de Oliveira Santos (UFRJ)

Maira Arruda Cardoso (UFRJ)


Cristóvão Antunes de Lanna (UFRJ)

Daniel Vinicius Neves de Lima (UFRJ)

Luiz Fernando Hill de Moura Abicair

(UFRJ)


Brenda Barros Fabricio (UFRJ)

Carla Nathália Rodrigues Teixeira (UFRJ)

Dian Souza Garcia (UFRJ)

Julia Cristina da Silva Telles (UFRJ)

Matheus Luchetta da Fonseca (UFRJ)

Thamires de Oliveira Lourenço (UFRJ)

The Laboratory is focused on the

development of new tools, comprising

computational and experimental advanced

methods, aiming to improve the

understanding of biological processes at

molecular level. Those methods are mainly

applied to investigate microorganism vs.

environment (host) relationships. Some other

biological models are also under study, for

instance, prokaryote gene expression and

developmental biology.

Our research topics combine bioinformatics,

molecular biology tools to explore gene

expression regulation and protein

biochemistry and biophysics.


results obtained during the four years’ period

covered by this report (2013 to 2016):

A novel model for the complete RND

system

RND (resistance-nodulation-division)

transporters are found in several Gram-

negative bacteria species. These proteins

form a complex along with membrane fusion

proteins and outer membrane factors. This

complex acts as an efflux pump, transporting

several different molecules directly from the

cytoplasm to the extracellular medium.

Although the crystallographic structure of

each protein of the complex is known, the

complete complex assembly is not yet fully

characterized. In 2016, we proposed a new

model for the complete system that also

satisfies the volume obtained from the

cryoelectron-microscopy assay. In this

model, the AcrA helical domains are

interleaved to the helical domains of the

TolC protein, increasing the diameter of the


105

formed pore (Figure 1). We believe that this

model represents a better model for RND-

type efflux pump and might contribute to the

characterization of this system.

Figure 1. (a) Contact interface between the TolC

protomers (in yellow) and the AcrA protomers (in

green). The hydrophobic residues that form this

interface are highlighted in a sphere representation.

Residues that belong to the TolC protomers are

colored in dark grey, whilst residues that belong to

the AcrA protomers are colored in white. The

interface region was modeled using the

crystallographic structure of MacA (PDB code

4DK0), which consists of a homododecameric

assembly presenting a tip-to-tip interaction between

the helical domains; (b) superposition of the TolC

trimers: the crystallographic structure under PDB

ID 2XMN (represented as grey surface) and the

new proposed model, colored by chain (in green,

magenta and cyan spheres). The pore diameter was

measured as the distance from the β-carbon of

V370 from chains A (green) and B (cyan); (c)

complete structure of AcrB-AcrA-TolC complex

superimposed to the Cryo-EM map volume. The

AcrB are colored in red, AcrA in green and TolC in

yellow. The tip-to-tip arrangement between AcrA

and TolC helical domains is compatible with the

bulge in the Cryo-EM map, located at the interface

region. This superimposition was achieved using

the Chimera software; (d) schematic representation

of the different spatial arrangement of the helical

domains of AcrA (green) and TolC (yellow). On the

left, the representation of the model proposed by

Du et al.6 and on the right the model proposed in

this work.

MDeNM: a new method to analyse

proteins samples

Proteins are found in solution as ensembles

of conformations in dynamic equilibrium.

Exploration of functional motions occurring

on µs-ms time scales by Molecular

Dynamics (MD) simulations still remains

computationally challenging. Alternatively,

normal mode (NM) analysis is a well suited

method to characterize intrinsic slow

collective motions, often associated to

protein function, but the absence of

anharmonic effects preclude a proper

characterization of conformational

distributions in a multidimensional NM

space. Using both methods jointly appears as

an attractive approach that allows an

extended sampling of the conformational

space. In line with this view the MDeNM

(Molecular Dynamics with excited Normal

Modes) method presented here consists in

multiple-replicas short MD simulations in

which motions described by a given subset

of low frequency NMs are kinetically

excited. This is achieved by adding

additional atomic velocities along several

randomly determined linear combinations of

NM vectors, thus allowing an efficient

coupling between slow and fast motions.

The relatively high-energy conformations

generated with MDeNM are further relaxed

with standard MD simulations enabling to

determine free energy landscapes. Two

widely studied proteins were selected as

examples: hen egg lysozyme and HIV-1

protease. In both cases, MDeNM provides a

larger extent of sampling in a few

nanoseconds, outperforming long standard

MD simulations (Figure 2). It was noticed a

high degree of correlation with motions

inferred from experimental sources (X-ray,

EPR and NMR), and with free energy

estimations obtained by metadynamics.

Finally, the large sets of conformations

obtained with MDeNM can be used in a

better characterization of relevant dynamical

populations, allowing a better interpretation

of experimental data such as SAXS and

NMR spectra.


106

Figure 2: Quantitative analyses of flap dynamics.

The distance between K55Nζ atoms from each

monomer was used to measure the extent of

opening/closing. Normalized distributions obtained

with MDeNM conformational exploration protocol

and from EPR of a spin labeled PR are shown in

black and red, respectively. The distribution

obtained from a 200 ns standard MD simulation

starting from a closed conformation is presented in

green. Two extreme conformations obtained by 1.5

Å MRMS displacements along both directions of

the CM3 are given in the upper part of the graph.

Transcriptomes and proteomic analyses in

Chagas disease

The bloodsucking hemipteran Rhodnius

prolixus is a vector of Chagas’ disease,

which affects 7–8 million people today in

Latin America. In contrast to other

hematophagous insects, the triatomine gut is

compartmentalized into three segments that

perform different functions during blood

digestion. Therefore, we reported an analysis

of transcriptomes for each of the segments

using pyrosequencing technology.

Comparison of transcript frequency in

digestive libraries with a whole-body library

was used to evaluate expression levels.

Together, our findings presented a new view

of the triatomine digestive apparatus and will

help us understand trypanosome interaction

and allow insights into hemipteran metabolic

adaptations to a blood-based diet.

Furthermore, Trypanosoma cruzi proteins

with molecular weight between 30-34 kDa

have shown high reactivity in western blot

assays with serum samples from chagasic

individuals. However, in-depth analysis of

the constituents of these protein fractions has

not been performed. Therefore, we

performed the first report of an

immunoaffinity proteomic approach to

identify these immunodominant proteins.

The use of different sample preparation

methods allowed the identification of a

relatively high number of proteins. Seven

immunodominant proteins were identified by

coimmunoprecipitation with purified IgGs

from chagasic serum samples. Moreover, six

reactive peptide epitopes were detected in

four of these proteins by excision-epitope

mapping/mass spectrometry. Three-

dimensional structural models were obtained

for the immunoreactive peptides, which

correlated well with the linear B-cell epitope

prediction tools. These proteins represent

potential candidates for use as diagnostic

markers for Chagas disease.

Structural characterization of SmZF1 in

S. mansoni

Zinc finger proteins are widely found in

eukaryotes, representing an important class

of DNA-binding proteins frequently

involved in transcriptional regulation. In

Schistosoma mansoni, these regulatory

proteins are known to modulate

morphological and physiological changes,

having crucial roles in parasite development.

A previously described C2H2 zinc finger

protein, SmZF1, was shown to be present in

cell nuclei of different life stages of S.

mansoni and to activate gene transcription in

a heterologous system. Therefore, we

structurally characterized the protein using a

combination of experimental and in silico

methodologies and, unexpectedly, we found

an inconsistency on the originally reported

SmZF1 cDNA sequence. Our findings

revealed a larger coding sequence than

previously considered and also four instead

of three zinc finger motifs (figure3). Here we

characterize the new SmZF1 tridimensional

structure with comparative modeling

followed by molecular dynamics

simulations. Further, we identified new

putative DNA binding sites with sequence

analysis and obtained a putative complex

with docking. Finally, we investigated

potential genes under SmZF1 control. Taken

together, these results present a consistent

base to the structural and functional

characterization of SmZF1. Thus, proteins

capable of regulating gene transcription,

such as SmZF1, are extremely important for


107

the maintenance of the complex parasite life

cycle and can be useful in the search for new

potential drugs against schistosomiasis.

Figure 3. SmZF1 molecular model confirms the

presence of four zinc finger motifs. (A) The

proposed tridimensional structure of SmZF1 was

obtained by comparative modeling using

MODELLER with the Aart protein (PDB ID: 2I13)

as a structural template and visualized with

PyMOL. The DNA binding zinc fingers are colored

in red, green, and blue. (B) Detailed view of the zinc

ion coordination by the histidine and cysteine

residues in the third zinc finger from the SmZF1

model. (For interpretation of the references to color

in this figure legend, the reader is referred to the

web version of the article.)


1. PACHECO, ANA B.F.; GUEDES, I. A. ; Azevedo, S.M.F.O. . Is qPCR a Reliable Indicator of Cyanotoxin Risk in Freshwater?. Toxins, v. 8,

p. 172, 2016. http://dx.doi.org/10.3390/toxins8060172

2. TORRES, PEDRO HENRIQUE MONTEIRO ; PASCUTTI, PEDRO GERALDO* ; BISCH, PAULO MASCARELLO ; SILVA,

MANUELA LEAL DA . Alternative Model for RND-Type Efflux Pump. Journal of the Brazilian Chemical Society (Impresso), v. 27, p.

2383-2387, 2016. http://dx.doi.org/10.5935/0103-5053.20160125


1. COSTA, MAURICIO GARCIA DE SOUZA ; BATISTA, PAULO RICARDO ; BISCH, PAULO MASCARELLO ; PERAHIA, DAVID .

Exploring free energy landscapes of large conformational changes: Molecular Dynamics with Excited Normal modes. Journal of Chemical

Theory and Computation, v. 11, p. 150420160913007-2767, 2015. http://dx.doi.org/10.1021/acs.jctc.5b00003

2. DE SOUZA ALBERNAZ, MARTA ; WEISSMULLER, GILBERTO ; LINHARES ROSSI, ANDRE ; MALTA ROSSI, ALEXANDRE ;

SANTOS-OLIVEIRA, RALPH . Polymeric nano-hydroxyapatite coated with polylactic acid (PLA): Considering new possibilities for

radiopharmacy. Journal of Diagnostic Imaging In Therapy, V. 2, P. 9-17, 2015. http://dx.doi.org/10.17229/jdit.2015-0210-012

3. FLOQUET, NICOLAS ; COSTA, MAURICIO G.S. ; BATISTA, PAULO R. ; RENAULT, PEDRO ; BISCH, PAULO M. ; RAUSSIN,

FLORENT ; MARTINEZ, JEAN ; MORRIS, MAY C. ; PERAHIA, DAVID . Conformational Equilibrium of CDK/Cyclin Complexes by

Molecular Dynamics with Excited Normal Modes. Biophysical Journal (Print), v. 109, p. 1-11, 2015.

http://dx.doi.org/10.1016/j.bpj.2015.07.003

4. GOULART, CAROLINA L. ; BISCH, PAULO M. ; VON KRÜGER, WANDA M.A. ; HOMBLÉ, FABRICE . VCA1008: An Anion-

Selective Porin of Vibrio Cholerae. Biochimica et Biophysica Acta. Biomembranes, v. 1848, p. 680-687, 2015.



1. COSTA, MAURICIO GS ; BENETTI-BARBOSA, TÉCIO G ; DESDOUITS, NATHAN ; BLONDEL, ARNAUD ; BISCH, PAULO M ;

PASCUTTI, PEDRO G* ; BATISTA, PAULO R . Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates:

insights from molecular dynamics. BMC Genomics, v. 15, p. S5, 2014. http://dx.doi.org/10.1186/1471-2164-15-s7-s5

2. DE MEDEIROS, LUCIANO NEVES ; DOMITROVIC, TATIANA ; DE ANDRADE, PAULA CAVALCANTE ; FARIA, JANE ;

BARRETO BERGTER, ELIANA ; WEISSMÜLLER, GILBERTO ; KURTENBACH, ELEONORA . Ps d1 binding affinity towards fungal

membrane components as assessed by SPR: The role of glucosylceramide in fungal recognition and entry. Biopolymers (New York. Print), v.

102, p. n/a-n/a, 2014. http://dx.doi.org/10.1002/bip.22570

3. DE PATRICIO, BEATRIZ FERREIRA CARVALHO ; DE ALBERNAZ, MARTA SOUZA ; SARCINELLI, MICHELLE ALVARES ; DE

CARVALHO, SAMIRA MARQUES ; SANTOS-OLIVEIRA, RALPH ; WEISSMÜLLER, GILBERTO . Development of Novel

Nanoparticle for Bone Cancer. Journal of Biomedical Nanotechnology, v. 10, p. 1242-1248, 2014. http://dx.doi.org/10.1166/jbn.2014.1812

4. GUEDES, IAMÊ ALVES ; DA COSTA LEITE, DANIEL MOREIRA ; MANHÃES, LARISSA ALVES ; BISCH, PAULO MASCARELLO

; AZEVEDO, SANDRA M.F.O.E. ; PACHECO, ANA BEATRIZ FURLANETTO . Fluctuations in microcystin concentrations, potentially

toxic Microcystis and genotype diversity in a cyanobacterial community from a tropical reservoir. Harmful Algae, v. 39, p. 303-309, 2014.

http://dx.doi.org/10.1016/j.hal.2014.09.001

5. ISHIDA, KELLY ; CIPRIANO, TALITA FERREIRA ; ROCHA, G. M. ; WEISSMULLER, G. ; GOMES, FABIO ; Miranda, Kildare ;

ROZENTAL, SONIA . Silver nanoparticle production by the fungus Fusarium oxysporum: nanoparticle characterisation and analysis of

antifungal activity against pathogenic yeasts. Memórias do Instituto Oswaldo Cruz (Impresso), v. 109, p. 220-228, 2014.

http://dx.doi.org/10.1590/0074-0276130269

6. PEREIRA, GABRIELA GARRASTAZU ; SANTOS-OLIVEIRA, RALPH ; ALBERNAZ, MARTHA S. ; CANEMA, DANIEL ;

WEISMÜLLER, GILBERTO ; BARROS, EDUARDO BEDE ; MAGALHÃES, LUCIANA ; LIMA-RIBEIRO, MARIA HELENA

MADRUGA ; POHLMANN, ADRIANA RAFFIN ; GUTERRES, SILVIA S. . Microparticles of Aloe vera/vitamin E/chitosan: Microscopic,

a nuclear imaging and an in vivo test analysis for burn treatment. European Journal of Pharmaceutics and Biopharmaceutics, v. 86, p. 292-

300, 2014. http://dx.doi.org/10.1016/j.ejpb.2013.10.011

7. RIBEIRO, JOSÉ M. C. GENTA, FERNANDO A. SORGINE, MARCOS H. F. LOGULLO, RAQUEL MESQUITA, RAFAEL D. PAIVA-

SILVA, GABRIELA O. MAJEROWICZ, DAVID MEDEIROS, MARCELO KOERICH, LEONARDO TERRA, WALTER R. FERREIRA,

CLÉLIA PIMENTEL, ANDRÉ C. BISCH, PAULO M. LEITE, DANIEL C. DINIZ, MICHELLE M. P. JUNIOR, JOÃO LÍDIO DA S. G. V.

DA SILVA, MANUELA L. ARAUJO, RICARDO N. GANDARA, ANA CAROLINE P. BROSSON, SÉBASTIEN SALMON, DIDIER

BOUSBATA, SABRINA GONZÁLEZ-CABALLERO, NATALIA SILBER, ARIEL MARIANO ALVES-BEZERRA, MICHELE , KATIA

C. GONDIM, MARIO ALBERTO C. SILVA-NETO, GEORGIA C. ATELLA, HELENA ARAUJO, FELIPE A. DIAS, CARLA

POLYCARPO, RAQUEL J. VIONETTE-AMARAL, PATRICIA FAMPA, ANA CLAUDIA A. MELO, APARECIDA S. TANAKA,

http://dx.doi.org/10.3390/toxins8060172

http://dx.doi.org/10.5935/0103-5053.20160125

http://dx.doi.org/10.1021/acs.jctc.5b00003

http://dx.doi.org/10.17229/jdit.2015-0210-012

http://dx.doi.org/10.1016/j.bpj.2015.07.003


http://dx.doi.org/10.1186/1471-2164-15-s7-s5

http://dx.doi.org/10.1002/bip.22570

http://dx.doi.org/10.1166/jbn.2014.1812

http://dx.doi.org/10.1016/j.hal.2014.09.001

http://dx.doi.org/10.1590/0074-0276130269

http://dx.doi.org/10.1016/j.ejpb.2013.10.011


108

CARSTEN BALCZUN, JOSE HENRIQUE M. OLIVEIRA, RENATA L. S. GONC¸ALVES, CRISTIANO LAZOSKI, ROLANDO

RIVERA-POMAR, LUIS DIAMBRA, GU¨NTER A. SCHAUB, ELOI S. GARCIA, PATRICIA AZAMBUJA, GLORIA R. C. BRAZ,

PEDRO L. OLIVEIRA. An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus. PLoS

Neglected Tropical Diseases (Online), v. 8, p. e2594, 2014. http://dx.doi.org/10.1371/journal.pntd.0002594

8. SEGURA C ; CUESTA-ASTROZ, Y. ; BATISTA, C. N. ; ZALIS, M. ; VON KRUGER, W. M. A. ; BISCH, PAULO M . Partial

characterization of Plasmodium falciparum trophozoite proteome under treatment with quinine, mefloquine and the natural antiplasmodial

diosgenone. Biomédica (Bogotá), v. 34, p. 20-29, 2014. DOI: 10.1590/S0120-41572014000200010


1. BITAR, MAINÁ ; DRUMMOND, MARCELA GONÇALVES ; COSTA, MAURICIO GARCIA SOUZA ; LOBO, FRANCISCO PEREIRA

; CALZAVARA-SILVA, CARLOS EDUARDO ; BISCH, PAULO MASCARELLO ; MACHADO, CARLOS RENATO ; MACEDO,

ANDRÉA MARA ; PIERCE, RAYMOND J. ; FRANCO, GLÓRIA REGINA . Modeling the zing finger protein SmZF1 from Schistosoma

mansoni: Insights into DNA binding and gene regulation. Journal of Molecular Graphics & Modelling, v. 39, p. 29-38, 2013.

http://dx.doi.org/10.1016/j.jmgm.2012.10.004

2. CARNEIRO, R. L. ; PACHECO, ANA BEATRIZ FURLANETTO ; AZEVEDO, SANDRA MARIA FELICIANO DE OLIVEIRA . Growth

and Saxitoxin Production by Cylindrospermopsis raciborskii (Cyanobacteria) Correlate with Water Hardness. Marine Drugs, v. 11, p. 2949-

2963, 2013. http://dx.doi.org/10.3390/md11082949

3. FELÍCIO, DEISE FONSECA ; VIDAL, LEONARDO DA SILVA ; IRINEU, ROBERTO SILVA ; LEITÃO, ALVARO COSTA ; VON

KRUGER, WANDA ALMEIDA ; BRITTO, CONSTANÇA DE PAOLI ; CARDOSO, ANGÉLICA ; CARDOSO, JANINE SIMAS ; LAGE,

CLAUDIA . Overexpression of Escherichia coli nucleotide excision repair genes after cisplatin-induced damage. DNA Repair (Print), v. 12,

p. 63-72, 2013. http://dx.doi.org/10.1016/j.dnarep.2012.10.009

4. LERY, LETÍCIA M.S. ; GOULART, CAROLINA L. ; FIGUEIREDO, FELIPE R. ; VERDOORN, KARINE S. ; EINICKER-LAMAS,

MARCELO ; GOMES, FABIO M. ; MACHADO, EDNILDO A. ; BISCH, PAULO M. ; VON KRUGER, WANDA M.A. . A comparative

proteomic analysis of Vibrio cholerae O1 wild-type cells versus a phoB mutant showed that the PhoB/PhoR system is required for full growth

and rpoS expression under inorganic phosphate abundance. Journal of Proteomics (Print), v. 86, p. 1-15, 2013.


5. SEGURA, CESAR ; CUESTA-ASTROZ, YESID ; NUNES BATISTA, CAMILA ; ZALIS, MARIANO ; DE ALMEIDA VON KRÜGER,

WANDA MARIA ; MASCARELLO BISCH, PAULO . Caracterización parcial del proteoma del trofozoito de Plasmodium falciparum bajo

tratamiento con quinina, mefloquina y el antiplasmodial natural diosgenona. Biomédica (Bogotá), v. 34, p. 237-249, 2013.

http://dx.doi.org/10.7705/biomedica.v34i2.1700

6. VERISSIMO DA COSTA, GIOVANI CARLO ; LERY, LETICIA MIRANDA SANTOS ; DA SILVA, MANUELA LEAL ; MOURA,

HÉRCULES ; PERALTA, REGINA HELENA SARAMAGO ; VON KRÜGER, WANDA MARIA ALMEIDA ; BISCH, PAULO

MASCARELLO ; BARR, JOHN R. ; PERALTA, JOSÉ MAURO . The identification and characterization of epitopes in the 30 34kDa

Trypanosoma cruzi proteins recognized by antibodies in the serum samples of chagasic patients. Journal of Proteomics (Print), v. 80, p. 34-

42, 2013. http://dx.doi.org/10.1016/j.jprot.2012.11.001


http://dx.doi.org/10.1016/j.jmgm.2012.10.004

http://dx.doi.org/10.3390/md11082949

http://dx.doi.org/10.1016/j.dnarep.2012.10.009


http://dx.doi.org/10.7705/biomedica.v34i2.1700



109

LA 11- Associated Laboratory of Microscopy

Coordinator: Thais Cristina Baeta Soares Souto Padrón* – IMPPG/UFRJ

*With deep sadness we inform that Professor Thais Souto-Padrón passed away in July 2016.

Professor Ulysses Lins took over the administrative functions of the AL 11.


Ulysses Garcia Casado Lins

Fernanda de Ávila Abreu


Adam P. Hitchcock, Canada Research Chair in Materials Research CLS-CCRS, B.I.M.R,

McMaster University, Canada

Bechara Kachar, M.D. Section on Structural Cell Biology, NICDC, NIH, EUA.

Dennis A. Bazylinski, School of Life Sciences, University of Nevada, Las Vegas, USA.


Camila Marques Adade,

Moara Lemos,

Anne Cristine Silva Fernandes,

Roberta Cura das Neves,

Ana Carolina Vieira Araujo,

Lia Cardoso Rocha Saraiva Teixeira


Moara Lemos,

Anne Cristine Silva Fernandes,

Thiago Luiz Alves e Silva,

Roberta Cura das Neves,

Pedro Ernesto Lopes Leão,

Jefferson Bomfim Silva Cypriano


Luciana Cunha da Silveira Lobo,

Natália Nascimento Vieira,

Clarissa Werneck Ribeiro,

Marina Chao Campello


Camila Menezes Laudeauzer,

Dayanne Fernandes Medeiros,

Pamela Caroline do Nascimento Dias,

Daiana dos Santos Condé,

Carolina Rosas Ferreira,

Sidcley Silva de Lyra,

Luiza Toledo de Oliveira Figueira,

Mayara Gil de Castro Santos,

Eduardo Monteiro de Resende,

Renata Dupret de Roseira

- Technicians:

Venício Féo da Veiga

Tarcísio Nascimento Correa

Project: Surface of pathogenic

microorganisms: ultrastructure and role

in the parasite-host interaction.

This project consists of three sub-projects: 1)

Cell surface components analysis and its role

in parasite-host interaction; 2) Use of natural

compounds as alternative for chemotherapy

of leishmaniasis and Chagas' disease; 3)

Isolation, culture and characterization of

trypanosomes parasites of fish and

amphibians: Molecular, phylogenetic and

ultrastructural characterization.

In subproject 1 the main results were the

standardization of isolation methods for

extracellular vesicles (EVs) derived of

epimastigotes and trypomastigotes of

Trypanosoma cruzi and Leishmania

amazonensis promastigotes,

immunocytochemistry analysis of isolated

vesicles; detection of enzymatic activity in

EVs; participation of EVs in the process of


110

parasite-host interaction and the role of

phospholipase A2 independent of calcium in

control of vesicle fusion of endocytic

pathway / exocytic of parasites. We also

analyze the signaling process that mediate

the release of EVs by trypomastigotes of T.

cruzi belonging to the Y strain and clone

CL-Brener and observed that the release of

EVs by these two parasite samples is

controlled by intracellular signaling

pathways apparently distinct. In sub-project

2 use toxins of animal origin and their by-

products and synthetic drugs to assess their

potential use in experimental chemotherapy

for control of diseases caused by protozoa.

We have analyzed the trypanocidal activity

of an isolated peptide from the CRISP

protein family, of the brut poison of

Crotallus viridis viridis snail which we call

crovirina and also the action of the venom of

Apis mellifera and its by-product melittin.

We observed that these compounds trigger

distinct cell death processes in the different

developmental forms of T. cruzi and

Leishmania and that the IC50 value for the

amastigotes of T. cruzi is usually lower than

the values observed for the trypomastigote

form which encourages more further analysis

of these types of compounds. In the third

subproject the results were the development

of culture media that provided the first in

vitro culture in Brazil of parasites of fish

trypanosomes, the description of a new

species of parasites of fish trypanosome, the

first in Brazil to be described based on

structural and molecular data from blood

forms, and culture forms established in vitro

in the laboratory and the endosymbionts

description in the cytoplasm of

trypanosomes of frogs whose number and

arrangement differ from other symbionts

previously described in other

trypanosomatids.

Figure 1. Three-dimensional reconstruction of frog trypanosomes containing endosymbionts in their cytoplasm

by FIB-SEM. (A) Model showing an dividing epimastigote presenting two flagella (F1 and F2) and containing 9

bacteria in their cytoplasm. Bacteria are located near the kinetoplast (white arrow in B), the flagellar pocket

(white arrows in C), the nucleus (white arrows D and E) or near the cell membrane (black arrows B and C).

Acidocalcisomes (Ac), Bacterium-like organisms (BLO) Flagellar pocket (FP), Flagelum (F), Old Flagellum (F1),

New Flagelum (F2) kinetoplast (k) Nucleus (N). Scale bars = 2μm.


111

Project: Biology, diversity and

biomineralization in magnetotactic

bacteria.

The main subjects are:

1) Biology and diversity of magnetotactic

bacteria.

During the period, we advanced in the

description of magnetotactic bacteria in

extreme environments. To achieve that goal

we analyzed samples collected from

sediments with extreme conditions: high

temperature, low temperature, high salinity

and high sulfur content. At least four new

types of magnetotactic bacteria were

discovered and their morphological

(ultrastructure, mineral analysis of the

magnetosomes) and phylogenetic (16S

rDNA sequencing) characteristics were

described.

2) Cultivation of magnetotactic bacteria.

Magnetotactic bacteria are fastidious

microorganisms. But, to advance in the

understanding of the cell biology it is

mandatory to grow these cells in pure

cultures. For that we established a

collaboration effort with Professor Dennis

Bazylinski from University of Nevada, LV,

EUA. Dr. Bazylinski is one of the world

leading experts in magnetotactic

microorganisms. We have been able to

cultivate at least three strains of marine and

freshwater magnetotactic bacteria. We

isolated the first magnetotactic bacterium

capable of biomineralization of greigite

(Fe3S4) magnetosomes (see Figure below).

Also, we have been able to isolate and

cultivate one strain from sediments collected

in Brazil.

Figure 2. TEM images of strain BW-1. (A) Darkfield scanning TEM image of a magnetosome chain containing

both greigite (labeled B) and magnetite (labeled C). (B). High-magnification TEM image of greigite crystal

labeled in (A). (inset) SAED of crystal viewed along the [0-11] zone axis. Pattern is consistent with greigite. (C)

High-magnification TEM image of magnetite crystal labeled in (A). (inset) SAED pattern of crystal viewed along

the [-1-12] zone axis. (D) TEM image of a stained thin-section of a cell of BW-1 showing several magnetosomes

aligned in the cell. Dark, intracellular, electron-dense mass represents large inclusion that is also visible by use

of light microscopy. (E) High-magnification TEM image of magnetosomes in (D) showing that an electron-dense

layer surrounds the greigite crystals, suggesting the presence of a magnetosome membrane.


112


1. ABREU, FERNANDA ; ARAUJO, ANA CAROLINA V. ; LEÃO, PEDRO ; SILVA, KAREN TAVARES ; MARQUES DE CARVALHO,

FABÍOLA ; DE LIMA CUNHA, OBERDAN ; ALMEIDA, LUIZ GONZAGA ; GEURINK, COREY ; FARINA, MARCOS ; RODELLI,

DANIEL ; JOVANE, LUIGI ; PELLIZARI, VIVIAN H. ; DE VASCONCELOS, ANA TEREZA ; BAZYLINSKI, DENNIS A. ; LINS,

ULYSSES. Culture-independent characterization of novel psychrophilic magnetotactic cocci from Antarctic marine sediments.

Environmental Microbiology (Print), v. 1, p. 1-16, 2016. http://dx.doi.org/10.1111/1462-2920.13388

2. ARAUJO, ANA CAROLINA VIEIRA ; MORILLO, VIVIANA ; CYPRIANO, JEFFERSON ; TEIXEIRA, LIA CARDOSO ROCHA

SARAIVA ; LEÃO, PEDRO ; LYRA, SIDCLEY ; ALMEIDA, LUIZ GONZAGA DE ; BAZYLINSKI, DENNIS A. ; VASCONCELLOS,

ANA TEREZA RIBEIRO DE ; ABREU, FERNANDA ; LINS, ULYSSES . Combined genomic and structural analyses of a cultured

magnetotactic bacterium reveals its niche adaptation to a dynamic environment. BMC Genomics, v. 17, p. 726, 2016.

http://dx.doi.org/10.1186/s12864-016-3064-9

3. BRASIL, P. F., DE FREITAS, J. A., BARRETO, A. L. S., ADADE, C. M., DE SÁ, L. F. R., CONSTANTINO-TELES, P., TOLEDO, F. T.,

DE SOUSA, B. A, GONÇALVES, A. C., ROMANOS, M. T. V., COMASSETO, J. V., DOS SANTOS, A. A., TESSIS, A. C., SOUTO-

PADRÓN, T, SOARES, R. M. A., FERREIRA-PEREIRA, A. (2016). Antiproliferative and ultrastructural effects of phenethylamine

derivatives on promastigotes and amastigotes of Leishmania (Leishmania) infantum chagasi. Parasitology International.

4. COSTA, D. C. M., AZEVEDO, M. M. B. D., SILVA, D. O. E., ROMANOS, M. T. V., SOUTO-PADRÓN, T. C. B. S., ALVIANO, C. S., &

ALVIANO, D. S. (2016). In vitro anti-MRSA activity of Couroupita guianensis extract and its component Tryptanthrin. Natural Product

Research.

5. LEÃO, PEDRO ; TEIXEIRA, LIA C. R. S. ; CYPRIANO, JEFFERSON ; FARINA, MARCOS ; ABREU, FERNANDA ; BAZYLINSKI,

DENNIS A. ; LINS, ULYSSES . North-seeking magnetotactic in the Southern Hemisphere. Applied and Environmental Microbiology (Print),

p. AEM.01545-16-5602, 2016. http://dx.doi.org/10.1128/AEM.01545-16

6. TRUBITSYN, D. ; ABREU, F. ; WARD, B. ; TAYLOR, T. ; HATTORI, M. ; KONDO, S. ; TRIVEDI, U. ; STANILAND, S. ; LINS, U. ;

BAZYLINSKI, DENNIS . Draft Genome Sequence of Strain MV-1, a Marine Vibrioid Magnetotactic Bacterium. Genome Announcements,

v. 4, p. e01330-16, 2016. http://dx.doi.org/10.1128/genomeA.01330-16

7. ZHU, XIAOHUI ; HITCHCOCK, ADAM P. ; BAZYLINSKI, DENNIS A. ; DENES, PETER ; JOSEPH, JOHN ; LINS, ULYSSES ;

MARCHESINI, STEFANO ; SHIU, HUNG-WEI ; TYLISZCZAK, TOLEK ; SHAPIRO, DAVID A. . Measuring spectroscopy and

magnetism of extracted and intracellular magnetosomes using soft X-ray ptychography. Proceedings of the National Academy of Sciences of

the United States of America, v. 1, p. 201610260, 2016. http://dx.doi.org/10.1073/pnas.1610260114


1. ARAUJO, ANA ; ABREU, FERNANDA ; SILVA, KAREN ; BAZYLINSKI, DENNIS ; LINS, ULYSSES . Magnetotactic Bacteria as

Potential Sources of Bioproducts. Marine Drugs, v. 13, p. 389-430, 2015. http://dx.doi.org/10.3390/md13010389

2. BARROS EM, LEMOS M, SOUTO-PADRÓN T, GIAMBIAGI-DEMARVAL M. Phenotypic and genotypic characterization of biofilm

formation in Staphylococcus haemolyticus. Elaine M Barros, Moara Lemos, Thais Souto-Padrón, Marcia Giambiagi-deMarval. Current

Microbiology 70(6): 829-834, 2015. doi: 10.1007/s00284-015-0794-x.

3. LEMOS M, FERMINO BR, SIMAS-RODRIGUES C, HOFFMANN L, SILVA R, CAMARGO EP,TEIXEIRA MG, SOUTO-PADRÓN T.

Phylogenetic and morphological characterization of trypanosomes from Brazilian armoured catfishes and leeches reveal high species

diversity, mixed infections and a new fish trypanosome species. Parasite & Vectors, 8(1):573, 2015. doi: 10.1186/s13071-015-1193-7.

AL 11 main publications in 2014: 1. ABRAÇADO, LEIDA G, WAJNBERG, ELIANE, ESQUIVEL, DARCI M S, KEIM, CAROLINA N, SILVA, KAREN T, MOREIRA,

EMÍLIO T S, LINS, ULYSSES, FARINA, MARCOS. Ferromagnetic resonance of intact cells and isolated crystals from cultured and

uncultured magnetite-producing magnetotactic bacteria. Physical Biology (Online)., v.11, p.036006 - , 2014. doi: 10.1088/1478-

3975/11/3/036006.

2. ADADE C, CARVALHO AL, TOMAZ M, COSTA T, GODINHO J, MELO P, LIMA, AP, RODRIGUES J, ZINGALI R*, SOUTO-

PADRÓN T*. Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against trypanosomes and

Leishmania. Plos Negleted Tropical Dis. 8(10): e3252, 2014. doi: 10.1371/journal.pntd.0003252.*IN COLLABORATION WITH

ZINGALI [AL 4]

3. ARAUJO, ANA, ABREU, FERNANDA, SILVA, KAREN, BAZYLINSKI, DENNIS, LINS, ULYSSES. Magnetotactic Bacteria as Potential

Sources of Bioproducts. Marine Drugs. , v.13, p.389 - 430, 2015. doi: 10.3390/md13010389.

4. CURVELO JAR, PORTELA MB, ALVIANO DS, BARRETO ALS, SOUTO-PADRÓN T*, HOLANDINO C, SOARES RMA. Effect of

secretory leukocyte proteinase inhibitor (SLPI) on Candida albicans biological processes: a therapeutic alternative? Archives of Oral Biology.

59(9): 928–937, 2014. doi: 10.1016/j.archoralbio.2014.05.007.

5. DIAS FA, VASCONCELLOS LRC, ROMEIRO A, ATTIAS M*, SOUTO-PADRÓN T, LOPES AH. Transovum transmission of

trypanosomatid cysts in the milkweed bug, Oncopeltus fasciatus. Plos One. 9(9):e108746, 2014. doi: 10.1371/journal.pone.0108746. *IN

COLLABORATION WITH ATTIAS [AL 9]

6. GARCIA-SILVA MR, CABRERA-CABRERA F, NEVES RFC, SOUTO-PADRÓN T, DE SOUZA W, CAYOTA A. Gene expression

changes induced by Trypanosoma cruzi shed microvesicles in mammalian host cells. Relevance of tRNA-derived halve. BioMed Research

International 2014:305239, 2014. doi: 10.1155/2014/305239. *IN COLLABORATION WITH DE SOUZA (AL 9)

7. GARCIA-SILVA MR, NEVES RFC, FLORENCIA CABRERA-CABRERA F, SANGUINETTI J, MEDEIROS LC, ROBELLO C, NAYA

H, FERNANDEZ-CALERO T, SOUTO-PADRÓN T, DE SOUZA W, CAYOTA A. Extracellular vesicles shed by Trypanosoma cruzi are

linked to small RNA pathways, life cycle regulation and susceptibility to infection of mammalian cells. Parasitology Research. 113(1): 285-

304, 2014. doi: 10.1007/s00436-013-3655-1. *IN COLLABORATION WITH DE SOUZA (AL 9)

8. GAZOS-LOPES F, OLIVEIRA MM, HOELZ LVB, VIEIRA DP, MARQUES AF, NAKAYASU ES, GOMES MT, PASCUTTI PG*,

SOUTO-PADRÓN T, MONTEIRO RQ, LOPES AH, ALMEIDA IC. Purification and Structural Characterization of a Platelet-Activating

Lysophosphatidylcholine of Trypanosoma cruzi. Plos Negleted Tropical Dis. 8(8): e3077, 2014. doi: 10.1371/journal.pntd.0003077.

9. KOELLER CM, VAN DER WEL H, FEASLEY CL, ABREU FA, MONTALVÃO F, FAMPA P, DOS REIS FCG, ATELLA GC, SOUTO-

PADRÓN T, WEST CM, HEISE N. Golgi UDP-GlcNAc: polypeptide O-α-N-acetyl-D-glucosaminyltransferase-2 (TcOGNT2) regulates

trypomastigote production and function in Trypanosoma cruzi. Eukaryotic Cell - 13(10): 1312-1327, 2014. doi: 10.1128/EC.00165-14.

10. LEMOS M & SOUTO-PADRÓN T. Isolation and in vitro maintenance of trypanosomes from naturally infected and commercially important

Brazilian fish. Journal of Parasitology 100(5): 687-691, 2014. doi: 10.1645/14-502.1.

11. MORILLO, VIVIANA, ABREU, FERNANDA, ARAUJO, ANA C., DE ALMEIDA, LUIZ G. P., ENRICH-PRAST, ALEX, FARINA,

MARCOS, DE VASCONCELOS, ANA T. R., BAZYLINSKI, DENNIS A., LINS, ULYSSES, Isolation, cultivation and genomic analysis of

magnetosome biomineralization genes of a new genus of South-seeking magnetotactic cocci within the Alphaproteobacteria. Frontiers in

Microbiology (Online). , v.5, p.1 - , 2014. doi: 10.3389/fmicb.2014.00072. eCollection 2014.

12. NEVES RFC, FERNANDES ACS, MEYER-FERNANDES JR*, SOUTO-PADRÓN T. Trypanosoma cruzi secreted vesicles have acid and

alkaline phosphatase activities capable of increasing parasite adhesion and infection. Parasitology Research 113(8): 2961-2972, 2014. doi:

10.1007/s00436-014-3958-x. *IN COLLABORATION WITH MEYER-FERNANDES [AL17]


113


1. ABREU, FERNANDA, MORILLO, VIVIANA, NASCIMENTO, FABRÍCIA F, WERNECK, CLARISSA, CANTÃO, MAURICIO

EGIDIO, CIAPINA, LUCIANE PRIOLI, DE ALMEIDA, LUIZ GONZAGA PAULA, LEFÈVRE, CHRISTOPHER T, BAZYLINSKI,

DENNIS A, DE VASCONCELOS, ANA TEREZA RIBEIRO, LINS, ULYSSES. Deciphering unusual uncultured magnetotactic

multicellular prokaryotes through genomics. The ISME Journal (Print). , v.1, p.1 - 14, 2013. doi: 10.1038/ismej.2013.203

2. ABREU, FERNANDA, SILVA, KAREN TAVARES, LEÃO, PEDRO, GUEDES, IAME ALVES, KEIM, CAROLINA NEUMANN,

FARINA, MARCOS, LINS, ULYSSES. Cell Adhesion, Multicellular Morphology, and Magnetosome Distribution in the Multicellular

Magnetotactic Prokaryote Candidatus Magnetoglobus multicellularis. Microscopy and Microanalysis (Print). , p.535 - 543, 2013. doi:

10.1017/S1431927613000329.

3. ADADE CM, OLIVEIRA IRS, PAIS JAR, SOUTO-PADRÓN T.Melittin peptide kills Trypanosoma cruzi parasites generating different cell

death phenotypes. Toxicon. 69:227-239, 2013. doi: 10.1016/j.toxicon.2013.03.011.

4. ALMEIDA, FERNANDO P., VIANA, NATHAN B., LINS, ULYSSES, FARINA, MARCOS, KEIM, CAROLINA N. Swimming behaviour

of the multicellular magnetotactic prokaryote `Candidatus Magnetoglobus multicellularis¿ under applied magnetic fields and ultraviolet light.

Antonie Van Leeuwenhoek (Dordrecht. Online). , v.103, p.845 - 857, 2013. doi:10.1007/s10482-012-9866-0

5. ALVES E SILVA TL, VASCONCELOS LR, LOPES AH & SOUTO-PADRÓN T. The immune response of hemocytes of the insect

Oncopeltus fasciatus against the flagellate Phytomonas serpens. Plos One 8(8):e72076, 2013. doi: 10.1371/journal.pone.0072076.

6. DE SOUZA, W.; CARVALHO, T. M. U.; SOUTO-PADRÓN, T. Trypanosoma cruzi e Doença de Chagas. In: Wanderley de Souza. (Org.).

Protozoologia Médica. 1ed.Rio de Janeiro: Rubio, 2013, v. 1, p. 63-123. [CHAPTER BOOK] *IN COLLABORATION WITH DE

SOUZA (AL 9)

7. FERNANDES ACS, SOARES DC, SARAIVA EM, MEYER-FERNANDES JR & SOUTO-PADRÓN T. Different secreted phosphatase

activities in Leishmania amazonensis. FEMS Microbiol Lett 340: 117-128, 2013. doi: 10.1111/1574-6968.12080*IN COLLABORATION

WITH AL 17

8. HAGLER, A. N., RIBEIRO, J. R. A., PINOTTI, T., BRANDAO, L. R., PIMENTA, R. S., LINS, U., LEE, C.-F., HSIEH, C.-W.,

LACHANCE, M.-A., ROSA, C. A. Wickerhamiella slavikovae sp. nov. and Wickerhamiella goesii sp. nov., two yeast species isolated from

natural substrates. International Journal of Systematic and Evolutionary Microbiology (Print). , v.63, p.3099 - 3103, 2013.

doi: 10.1099/ijs.0.051953-0

9. KORENBLUM, ELISA, REGINA DE VASCONCELOS GOULART, FÁTIMA, DE ALMEIDA RODRIGUES, IGOR, ABREU,

FERNANDA, LINS, ULYSSES, ALVES, PÉRICLES, BLANK, ARIE, VALONI, ÉRIKA, SEBASTIÁN, GINA V, ALVIANO, DANIELA,

ALVIANO, CELUTA, SELDIN, LUCY. Antimicrobial action and anti-corrosion effect against sulfate reducing bacteria by lemongrass

(Cymbopogon citratus) essential oil and its major component, the citral. AMB Express. , v.3, p.44 - , 2013. doi: 10.1186/2191-0855-3-44.

10. LEFÈVRE, CHRISTOPHER T., TRUBITSYN, DENIS, ABREU, FERNANDA, KOLINKO, SEBASTIAN, JOGLER, CHRISTIAN, DE

ALMEIDA, LUIZ GONZAGA PAULA, DE VASCONCELOS, ANA TEREZA R., KUBE, MICHAEL, REINHARDT, RICHARD, LINS,

ULYSSES, PIGNOL, DAVID, SCHÜLER, DIRK, BAZYLINSKI, DENNIS A., GINET, NICOLAS. Comparative Genomic Analysis of

Magnetotactic Bacteria from the Deltaproteobacteria Provides New Insights into Magnetite and Greigite Magnetosome Genes

Required for Magnetotaxis. Environmental Microbiology (Print)., v.15, p.2712 - 2735, 2013. doi: 10.1111/1462-2920.12128

11. LEFÈVRE, CHRISTOPHER T., TRUBITSYN, DENIS, ABREU, FERNANDA, KOLINKO, SEBASTIAN, DE ALMEIDA, LUIZ

GONZAGA PAULA, DE VASCONCELOS, ANA TEREZA R., LINS, ULYSSES, SCHÜLER, DIRK, GINET, NICOLAS, PIGNOL,

DAVID, BAZYLINSKI, DENNIS A. Monophyletic Origin of Magnetotaxis and the First Magnetosomes. Environmental Microbiology

(Print), 15(8): 2267-2274. 2013. doi: 10.1111/1462-2920.12097.

12. LEMOS M, SOUZA CSF, COSTA SC, SOUTO-PADRÓN T, D’AGOSTO M. Isolation and in vitro culture of trypanosomes from

Leptodactylus ocellatus frogs from the Atlantic Forest. Journal of Parasitology 99(1): 164-167, 2013. doi: 10.1645/GE-2949.1. 13. MARINHO FA, OLIVEIRA SSC, GONÇALVES DS, MATTEOLI FP, SEABRA SH, OLIVEIRA ACS, BELLIO M, OLIVEIRA SS,

SOUTO-PADRÓN T, D’AVILA-LEVY CM, SANTOS ALS, BRANQUINHA MH. The calpain inhibitor MDL28170 induces apoptosis in

Leishmania amazonensis promastigotes. Plos One 9(1):e87659, 2014. doi: 10.1371/journal.pone.0087659. 14. PACHECO DA ROSA, JULIANA, KORENBLUM, ELISA, FRANCO-CIRIGLIANO, MARCELLA NOVAES, ABREU, FERNANDA,

LINS, ULYSSES, SOARES, ROSÂNGELA M. A., MACRAE, ANDREW, SELDIN, LUCY, COELHO, ROSALIE R. R. Streptomyces

lunalinharesii Strain 235 Shows the Potential to Inhibit Bacteria Involved in Biocorrosion Processes. BioMed Research International. ,

v.2013, p.1 - 10, 2013. doi: 10.1155/2013/309769

15. SILVA, K. T., LEAO, P. E., ABREU, F., LOPEZ, J. A., GUTARRA, M. L., FARINA, M., BAZYLINSKI, D. A., FREIRE, D. M. G., LINS,

U. Optimized magnetosome production and growth by the magnetotactic vibrio Magnetovibrio blakemorei strain MV-1 using statistical

experimental design. Applied and Environmental Microbiology (Print). , v.79, p.2823 - 2827, 2013. doi: 10.1128/AEM.03740-12

16. SOUTO-PADRÓN, T. Métodos de Diagnóstico de Doenças causadas por Protozoários. In: Wanderley de Souza. (Org.). Protozoologia

Médica. 1ed.Rio de Janeiro: Rubio, 2013, v. 1, p. 343-375. [CHAPTER BOOK] *IN COLLABORATION WITH DE SOUZA (AL 9)



114

AL 12 - Associated Laboratory of Cellular Ultrastructure - Coodinator:

Marlene Benchimol – IBCCF/UFRJ and Unigranrio


Antonio Pereira Neves- Fiocruz Pernambuco - Centro de pesquisas Aggeu Magalhães.


Natalia de Miguel- Argentina-CONICET

- Postdoctoral fellows: Victor do Valle Midlej - UFRJ

Caroline Spitz - UFRJ


Leidiane Coelho de Lima - Unigranrio


Priscila Laviola - Unigranrio


Felipe Louzada Rubim - USU

Our group studies four important parasites:

Trichomonas vaginalis, Tritrichomonas foetus,

Trichomonas tenax and Giardia intestinalis.

Tritrichomonas foetus is a serious veterinary

pathogen that causes bovine trichomoniasis, a

sexually transmitted disease that results in

reproductive failure and considerable economic

losses in areas of natural breeding. Evidences

suggest that plasma membrane lipids are

nonhomogeneously distributed and that

microdomains with specialized functions exist in

the plasma membrane. a lipid raft, is a highly

ordered, less-fluid and tightly packaged

membrane domain enriched in cholesterol (or

other sterols), glycosphingolipids, and

phospholipids with a higher degree of saturated

fatty acyl chains than those of the rest of the

membrane. We demonstrated the presence of the

lipid rafts in plasma membrane of the T. foetus,

showing that these microdomains are cholesterol

enriched and possess GM1 molecules. Moreover,

we have shown that lipid rafts do not have

participation on adhesion to host cells. In

addition, we used agents that disrupt and

disorganize the plasma membrane showing that

these procedures affected cell division of the

parasite and induced of the formation of the

endoflagellar forms of the T. foetus. We

demonstrated that trophozoites and endoflagellar

forms present a different plasma membrane

organization. We identified and characterized

raft-like domains in this pathogen and verified if

there is a participation of these domains on

interaction of this parasite with host-cells in

vitro.

There are very few studies concerning the Golgi

in trichomonads. We have used monoclonal

antibodies raised against Golgi of T. foetus and

used as a tool on morphologic and biochemical

studies of this organelle. Among the antibodies

produced, one was named mAb anti-Golgi 20.3,

which recognized specifically the Golgi complex

by fluorescence and electron microscopy (Figure

1).


115

Fig. 1. (a–d) Tritrichomonas foetus labelled with mAb anti-Golgi 20.3 conjugated with Alexa 546 secondary antibody and

with the lectin HPA-Alexa 488 conjugated. (a) DIC; (b) immunofluorescence with mAb anti-Golgi 20.3-Alexa 546; (c)

fluorescence with HPA-Alexa 488; (d) Merge. Note that the Golgi complex of T. foetus is labelled with both compounds.

By immunoblotting this antibody recognized two

proteins with 60 kDa and 66 kDa that were

identified as putative beta-tubulin and adenosine

triphosphatase, respectively. The mAb 20.3 also

recognized the Golgi complex of the

Trichomonas vaginalis, a human parasite. In

addition, the nucleotide coding sequences of

these proteins were identified and included in the

T. foetus database, and the 3D structure of the

proteins was predicted. In conclusion, this study

indicated: (1) adenosine triphosphatase is present

in the Golgi, (2) ATPase is conserved between T.

foetus and T. vaginalis, (3) there is new

information concerning the nucleic acid

sequences and protein structures of adenosine

triphosphatase and beta-tubulin from T. foetus

and (4) the mAb anti-Golgi 20.3 is a good Golgi

marker and can be used in future studies.

T. foetus contains organelles that are common to

all eukaryotic cells as well as uncommon cell

structures such as hydrogenosomes and a

complex and elaborate cytoskeleton that

constitutes the mastigont system. The mastigont

system is mainly formed by several

proteinaceous structures that are associated with

basal bodies, the pelta-axostylar complex and the

costa. Although the structural organization of

trichomonad cytoskeletons has been analyzed

using several techniques, observation using a

new generation of scanning electron microscopes

with a resolution of 0.8 nm has allowed more

detailed visualization of the three-dimensional

organization of the mastigont system. Moreover,

we revealed the presence of new structures, such

as the costa accessory filament, and the presence

of two groups of microtubules that form the

pelta-axostylar system using ultra-high resolution

scanning electron microscopy. More importantly,

a new accessory was observed running along the

right-hand side of the costa. Similarly the costa,

the accessory filament forms a striated pattern,

but these structures are originated in sites with

opposite directions. To the best of our

knowledge, this report is the first description of

this structure.

Changes in the structural organization of the

cytoskeleton of T. foetus during trophozoite-

pseudocyst transformation was observed in our

analyses using high resolution scanning electron

microscopy and thus we were able to observe

changes that took place during trophozoite-

pseudocyst transformation. The results obtained

confirm previous studies and add new structural

information on the organization of cytoskeletal

structures. We observed that the axostyle and

costa of pseudocysts modify and acquired a

curved shape. In addition, in

multinucleated/polymastigont pseudocysts the

organization of the cytoskeleton revealed that the

costa presents variable conformation being even

curved (Figure 2). The costa accessory structure

as well as a network of filaments connecting this

structure to the region where the recurrent

flagellum associates to the protozoan body, were

not seen in pseudocysts. Moreover, the axostyle

was fragmented during trophozoite-pseudocyst

transformation.


116

Figure 2. Cytoskeleton of the pseudocyst as seen by high

resolution SEM. Note that the axostyle (Ax) is seen

around the nucleus (N) as well the flagella (F) and the

costa (C) displays a curved appearance.

We also were able to improve the knowledge on

the ultrastructure and biochemistry of the costa

of T. foetus. The cell fractionation technique was

performed to obtain an enriched fraction of the

costa, which was analyzed by negative staining,

revealing three distinct regions named as head,

neck and body, according to the shape and

periodicity pattern. The structure complexity was

proved by Fourier transform that demonstrated

that the eletronlucent bands present sub bands

with regular patterns. In addition, protein

composition of the costa was evaluated by uni-

and two-dimensional electrophoresis and liquid

chromatography coupled with tandem mass

spectrometry (LC-MS/MS) that allowed the

identification of 42 hypothetical proteins of

which fourteen are majority in the fraction and

present potential to compose the costa structure.

These proteins exhibit uncharacterized domains,

showing that the costa structure would be formed

by a new class of proteins, different from those

previously described in other organisms.

However, the knowledge of these protein

sequences obtained here, will be help in future

studies to determine their actual locations and

functions.

We also studied the proteasomes, which are

intracellular complexes that control selective

protein degradation in organisms ranging from

Archaea to higher eukaryotes. These structures

have multiple proteolytic activities that are

required for cell differentiation, replication and

maintaining cellular homeostasis. Here, we

document the presence of the 20S proteasome in

the protist parasite Tritrichomonas foetus.

Complementary techniques, such as a

combination of whole genome sequencing

technologies, bioinformatics algorithms, cell

fractionation and biochemistry and microscopy

approaches were used to characterise the 20S

proteasome of T. foetus. The 14 homologues of

the typical eukaryotic proteasome subunits were

identified in the T. foetus genome. Alignment

analyses showed that the main regulatory and

catalytic domains of the proteasome were

conserved in the predicted amino acid sequences

from T. foetus-proteasome subunits.

Immunofluorescence assays using an anti-

proteasome antibody revealed a labelling

distributed throughout the cytosol as punctate

cytoplasmic structures and in the perinuclear

region. Electron microscopy of a T. foetus-

proteasome-enriched fraction confirmed the

presence of particles that resembled the typical

eukaryotic 20S proteasome. Fluorogenic assays

using specific peptidyl substrates detected

presence of the three typical peptidase activities

of eukaryotic proteasomes in T. foetus. As

expected, these peptidase activities were

inhibited by lactacystin, a well-known specific

proteasome inhibitor, and were not affected by

inhibitors of serine or cysteine proteases. During

the transformation of T. foetus to endoflagellar

form (EFF), also known as pseudocyst, we

observed correlations between the EFF formation

rates, increases in the proteasome activities and

reduced levels of ubiquitin-protein conjugates.

The growth, cell cycle and EFF transformation of

T. foetus were inhibited after treatment with


117

lactacystin in a dose-dependent manner.

Lactacystin treatment also resulted in an

accumulation of ubiquitinated proteins and

caused increase in the amount of endoplasmic

reticulum membranes in the parasite. Taken

together, our results suggest that the ubiquitin-

proteasome pathway is required for cell cycle

and EFF transformation in T. foetus.

In addition, we investigated the effects of

gliotoxin, a proteasome inhibitor, on the cell

growth, replication, ultrastructure, DNA integrity

and proteasomal proteolytic activity of the protist

parasite Tritrichomonas foetus. The effect of

gliotoxin on the transformation of T. foetus to

endoflagellar form (EFF), also known as

pseudocyst, was investigated. Gliotoxin inhibited

the culture growth, arrested cell cycle, and

provoked a trichomonacidal effect in a dose-

dependent manner. Parasites treated with

gliotoxin displayed features typical of cell death,

such as membrane blebbing, concentric

membrane whorls containing remnants of

organelles, intense cytosolic and nuclear

vacuolization, chromatin condensation, DNA

fragmentation, cytoplasmic disintegration and

plasma membrane disruption. The proteasomal

peptidase activity was inhibited by gliotoxin in a

dose-dependent manner. Gliotoxin-treatment also

induced an irreversible EFF transformation in a

dose/time-dependent manner. We compared

morphological characteristics between gliotoxin-

and cold-induced EFF parasites. Our results

suggest that gliotoxin could induce EFF

transformation by a mechanism distinct from that

provoked by cold-temperature. This study further

contribute to a better understanding of the role of

proteasome system in cell cycle, cell death and

EFF transformation in T. foetus.

Trichomonas tenax is considered a commensal

organism found under poor oral hygiene

conditions. T. tenax presents morphological

similarities with T. vaginalis, and there is doubts

concerning whether this protist is a parasite and

whether it is a genetic variant of T. vaginalis.

This study aimed to investigate the capacity of T.

tenax to cause mammalian cell damage and

compare its cytotoxicity with that of T. vaginalis.

Protozoan-host cell interaction assays were

performed with Madin-Darby canine kidney,

HeLa, and gum cells and 3D spheroids, which

were examined by scanning electron and

transmission electron microscopy. Cellular

viability experiments were also performed. T.

tenax attached and had different forms when

interacting with mammalian cells and caused

damage with time-dependent host-cell viability.

We observed that T. tenax produced plasma

membrane projections and phagocytosed portions

of the mammalian cells. In addition, T. tenax

caused membrane blebbing and apoptotic bodies

in HeLa cells, thus inducing cell death. Spheroids

were used in experiments interaction with T.

tenax wich provoked damage to these cells

(Figure 3). This study shows that T. tenax fulfills

the requisites of a parasite, causing damage to

different mammalian cells and behaving

similarly to T. vaginalis when in contact with

target cells in vitro.

Figure 3. Scanning electron microscopy of the

interaction between 3D spheroids (composed of gum

epithelial cells and fibroblasts) and Trichomonas tenax

(a, c, e) or T. vaginalis JT (b, d, f). After 2 h of

interaction (a, b), the protozoa are seen attached to the

spheroids. (c) After 6 h of interaction, the 3D spheroids

have already been damaged by the T. tenax, while T.

vaginalis JT (d) is adhered to and clustered around the

spheroid. (e) The spheroid is coated by T. tenax after 24

h of interaction. (f) The spheroid has some attached T.

vaginalis cells, but no apparent damage was observed.


118

The parasite Trichomonas vaginalis is the

causative agent of trichomoniasis, a prevalent

sexually transmitted infection. Here, we report

the cellular analysis of T. vaginalis tetraspanin

family (TvTSPs). This family of membrane

proteins has been implicated in cell adhesion,

migration and proliferation in vertebrates. We

observed that the expression of several members

of the family is up regulated upon contact with

vaginal ectocervical cells (VECs). We found that

most TvTSPs are localized on the surface and

intracellular vesicles and that their C-terminal

intracellular tails of surface TvTSPs are

necessary for proper localization. Finally, we

showed that the formation of clumps of T.

vaginalis is mediated, at least in part, by TSP8

suggesting a role for this protein in parasite:

parasite communication.

Giardia lamblia is a protozoan parasite that

presents both trophozoite and cyst forms. Here

the distribution of different sugar residues and

the origin of carbohydrate components of the

cyst wall was studied using transmission electron

microscopy, ultrastructural cytochemistry for

carbohydrate detection and

immunocytochemistry. Immunofluorescence

with anti-CWP1 and several gold- and

fluorescent-labeled lectins, such as WGA, HPA,

WFA, DBA, UEAI, LCA, BSII, and Con A were

also used. In trophozoites an intense labeling was

observed when WGA, WFA and DBA were

probed. Interestingly, an electron lucent cell

compartment (ELVs), positive for carbohydrates,

was found in encysting cells. The ELVs are

distinct from the ESV because: (1) it is electron

lucent, whereas the ESVs are electron dense; (2)

it does not react with antibodies against cyst wall

proteins; (3) its contents is positive for

carbohydrates, whereas the ESVs display a

negative reaction; (4) this cell compartment

exhibits a positive labeling for DBA lectin,

indicating the presence of N-acetyl-

galactosamine, whereas the ESVs are negative.

To test whether the ELVs could be vesicles in the

endocytic pathway endocytic markers were used

showing a negative result. Thus we propose that

the ELVs could represent a new structure

involved in the cyst wall formation.

The success of the Giardia infection is due to its

simple cell cycle that includes two

developmental stages: the trophozoite and the

cyst. The transformation of the trophozoites into

cysts is known as the encystation process,

wherein a number of modifications occur,

including (a) the appearance of large vesicles,

known as encystation specific vesicles (ESVs),

that are rich in proteins that will assemble the

cyst wall; (b) the appearance of the encystation

carbohydrate-containing vesicles (ECVs), also

involved in cyst wall formation; (c) a

reorganization of the internal cytoskeletal

structures; (d) the internalization of the flagella,

and (e) the synthesis of a rigid cyst wall.

The mitosome is a double-membrane bounded

organelle found in few unicellular eukaryotes,

including the human intestinal parasitic

protozoan Giardia intestinalis that also lacks

mitochondria and peroxisomes and has been

considered to be among the earliest branching

eukaryotes. This flagellated protozoan grows in

vitro as trophozoites and under some conditions

differentiates into cysts, characterized by the

absence of flagella, a rounded shape and the

presence of a cyst wall. Using antibodies that

recognize two proteins present in the mitosome,

the heat-shock protein 70 (mitHSP70) and the

giardial chaperonin 60 (giCpn60), we analyzed

the presence and distribution of the mitosomes

during the cell cycle as well as during the process

of trophozoite-cyst transformation by confocal

laser scanning microscopy and Western blotting.

Our observations show that at early stages of the

differentiation process (around 12hs) there is a

significant decrease in the extent of labeling of

the cells and the number of mitosomes, which

almost disappear after 21hs, followed by

recovery in the cyst stage. This information was

confirmed by mRNA expression analysis thus

indicating a process of modulation of formation

of mitosomes during the life cycle of G.

intestinalis. Electron microscopy tomography

allowed the three dimensional reconstruction of

mitosomes revealing the presence of rounded as

well as elongated organelles.


119

AL 12 main publications in 2016: 1. BENCHIMOL, M.; PEREIRA-NEVES, A.; DE SOUZA, W. Pathogenesis of Trichomonas vaginalis in Humans. In: Human Emerging

and Re-emerging Infections: Viral & Parasitic Infections, Volume I, First Edition. Edited by Sunit K. Singh. 2016 John Wiley & Sons,

Inc. Published 2016 by JohnWiley & Sons, Inc. [CHAPTER BOOK] *IN COLLABORATION WITH DE SOUZA (AL 9).

2. CAMPOS, L. M.; RIOS, E.; GUAPYASSU, L.; MIDLEJ V; ATELLA, G.; HERCULANO, S.; BENCHIMOL, M.; MERMELSTEIN, C.

S.; COSTA, M. Alterations in zebrafish development induced by simvastatin: comprehensive morphological and physiological study,

focusing on muscle. Experimental Biology and Medicine (Maywood. Online), v. -, p. 1-11, 2016.

http://dx.doi.org/10.1177/1535370216659944

3. MIDLEJ V ; SILVA, R.; SOUZA, W. ; BENCHIMOL, M. . Mitosomal chaperone modulation during the life cycle of the pathogenic

protist Giardia intestinalis. EUROPEAN JOURNAL OF CELL BIOLOGY, p. pii: S0171-933-17, 2016.

http://dx.doi.org/10.1016/j.ejcb.2016.08.005 *IN COLLABORATION WITH DE SOUZA (AL 9).

4. NETO, E. ; MACHADO, R. ; GAMA, S. ; RIBEIRO, C. ; MIDLEJ V ; BENCHIMOL, M. ; V. MORANDI ; BARJA-FIDALGO C .

'Priming endothelial cells with a melanoma-derived matrix triggers the alpha v beta3/VEGFR2 axis activation. Journal of Cellular

Physiology (Print), v. 1, p. 1-16, 2016.

5. NEVES NETO, A. P.; BENCHIMOL, MARLENE. The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and induces

an irreversible pseudocystic transformation and cell death in Tritrichomonas foetus. Parasitology Research (1987. Print), p. 34-49, 2016.

http://dx.doi.org/10.1007/s00436-016-5061-y

6. PEROBELLI, S. M. ; MERCADANTE, A. C. ; GALVANI, R. G. ; GONÇALVES-SILVA, T. ; ALVES, A. P. G. ; NEVES NETO, A. P.

; BENCHIMOL, MARLENE ; Alberto Nóbrega ; Adriana Bonomo . G-CSF induced suppressor IL-10+ 1 neutrophils promotes Tregs,

which inhibit 2 GVHD on a long lasting and specific way. The Journal of Immunology (1950), 2016.

AL 12 main publications in 2015: 1. CAMPOS, L. M.; MORRIS, EDUARDO A; MIDLEJ, V; ATELLA, GEORGIA; HOUZEL, SUZANA H; BENCHIMOL, M.,

MERMELSTEIN, CLÁUDIA DOS SANTOS; COSTA, MANOEL. Structural Analysis of Alterations in Zebrafish Muscle Differentiation

Induced by Simvastatin and Their Recovery with Cholesterol. The Journal of Histochemistry and Cytochemistry. , v.63, p.427 - 437,

2015.

2. COCERES, V., NIEVAS, Y., MIDLEJ V, FRONTERA, L, BENCHIMOL, M., JOHNSON, P., DE MIGUEL, N.The C-terminal tail of

tetraspanin proteins regulates their intracellular distribution in the parasite <i>T</i> <i>richomonas vaginalis</i>. Cellular Microbiology

(Print). , p.n/a - n/a, 2015.

3. DE ANDRADE ROSA, IVONE, DESOUZA, W., BENCHIMOL, M. Changes in the structural organization of the cytoskeleton of

Tritrichomonas foetus during trophozoite-pseudocyst transformation. Micron (Oxford. 1993). , v.73, p.28 - 35, 2015. *IN

COLLABORATION WITH DE SOUZA (AL 9).

4. ESDRAS-TEIXEIRA, DIRCEU; RIBEIRO, LUIZ CARLOS DOS SANTOS; CASSIANO, KEILA MARA; MASUDA, MASAKO OYA;

BENCHIMOL, MARLENE. Avaliação institucional em Ciências Biológicas nas modalidades presencial e a distância: percepção dos

egressos. Ensaio (Fundação Cesgranrio. Impresso). , v.23, p.159 - 180, 2015.

5. GADELHA, A. P.; BENCHIMOL, M., DESOUZA, W. Helium ion microscopy and ultra-high-resolution scanning electron microscopy

analysis of membrane-extracted cells reveals novel characteristics of the cytoskeleton of Giardia intestinalis. Journal of Structural Biology

(Print). p.S1047- - 8477(15)00102-1, 2015. *IN COLLABORATION WITH DE SOUZA (AL 9).

6. NEVES NETO, A. P., GONZAGA, L., MENNA-BARRETO, BENCHIMOL, M. Characterisation of 20S proteasome in Tritrichomonas

foetus and its role during the cell cycle and transformation into endoflagellar form. Plos One. , v.10, p.e0129165 - , 2015.

7. RIBEIRO, L. C. S., SANTOS, C. BENCHIMOL, M. Is Trichomonas tenax a Parasite or a Commensal?. Protist (Jena. Print). , v.166,

p.196 - 210, 2015.

8. SOUZA, D. B., GREGÓRIO, BIANCA MARTINS; BENCHIMOL, M., NASCIMENTO, FERNANDA AMORIM DE MORAIS.

Evaluation of the Glomerular Filtration Barrier by Electron Microscopy In: Evaluation of the Glomerular Filtration Barrier by Electron

Microscopy.1 ed.Rijeka : In Tech, 2015, p. 52-108. [CHAPTER BOOK]

AL 12 main publications in 2014: 1. BENCHIMOL, MARLENE, ENGEL J, TANG KS, DE SOUZA, W. Cell Biology of Pathogenic Protozoa and their interaction with host

cells. Journal of Biomedicine and Biotechnology (Online). , v.2014, p.14318 - , 2014*IN COLLABORATION WITH DE SOUZA (AL

9).

2. COUTINHO, MARIA ALICE DE ALMEIDA; SANTIAGO, M. F., AGUILA, E. M., BENCHIMOL, MARLENE, PASCHOALIN, V. M.

F., SILVA, J. T. International Journal of Current Microbiology and Applied Sciences. International Journal of Current Microbiology and

Applied Sciences. , v.3, p.912 - 927, 2014.

3. ESDRAS-TEIXEIRA, D.; RIBEIRO, L. C. S., MASUDA, MASAKO; CASSIANO, K. M., BENCHIMOL, M. Perfil e destino

ocupacional de egressos graduados em Ciências Biológicas nas modalidades a distância e presencial. Ensaio: Pesquisa em Educação em

Ciências (Impresso). , v.6, p.67 - 84, 2014.

4. FERNANDES, FELIPE; ESDRAS-TEIXEIRA, D. BENCHIMOL, MARLENE A Malária e o plasmódio. Rio de Janeiro-RJ : INMETRO,

2014, v.1. p.36. [BOOK]

5. NEVES NETO, A. P., FERNANDES, J. R. M., ENCINA, J., BENCHIMOL, M. Tritrichomonas foetus: Characterisation of ecto-

phosphatase activities in the endoflagelar form and their possible participation on the parasite¿s transformation and cytotoxicity.

Experimental Parasitology. , v.2, p.78 - 88, 2014.

6. POSSIDONIO, A. C.; SOARES, C.P.; PORTILHO, D.; MIDLEJ, V.; BENCHIMOL, M.; BUTLER-BROWNE, G.; COSTA, M.;

MERMELSTEIN, C.S.Differences in the expression and distribution of flotillin-2 in chick mice and human muscle cells. Plos One. , v.9,

p.e103990 - , 2014.

7. ROCHA D., ROSA, I., SOUZA, W., BENCHIMOL, M. The effect of 3-(biphenyl-4-yl)-3-hydoxyquinuclidine (BPQ-OH) and

metronidazole on Trichomonas vaginalis: a comparative study. Parasitology Research (1987. Print). , v.12, p.13 - 23, 2014. *IN


8. ROSA, IVONE DE ANDRADE, ATELLA, GEORGIA, BENCHIMOL, MARLENE. Tritrichomonas foetus Displays Classical

Detergent-resistant Membrane Microdomains on its Cell Surface. Protist (Jena. Print). , v.187, p.12 - 23, 2014.

AL 12 main publications in 2013: 1. BENCHIMOL, M. Protozoologia Médica In: Trichomonas.1 ed.Rio de Janeiro : RUBIO, 2013, v.1, p. 251-276. [CHAPTER BOOK]

2. BENCHIMOL, M., CARVALHO, H. A Célula. Barueri : Manole, 2013, v.1. p.590. [BOOK]

3. BENCHIMOL, M., MIDLEJ V, MEINIG, ISADORA PEIXOTO; DESOUZA, W. A New Set of Carbohydrate-positive Vesicles in

Encysting Giardia lamblia. Protist (Jena. Print). , v.164, p.261 - 271, 2013. *IN COLLABORATION WITH DE SOUZA (AL 9).

4. BENCHIMOL, M., RENDON-GANDARILLA, F. J., RAMON-LUING, L. L. A., ORTEGA-LOPEZ, J., ARROYO, R., ROSA, I. The

TvLEGU-1, a Legumain-Like Cysteine Proteinase, Plays a Key Role in Trichomonas vaginalis Cytoadherence. BioMed Research

International. , v.2013, p.1 - 18, 2013.

5. CÁRDENAS-GUERRA, ROSA ELENA; ARROYO, R.; ROSA, I.; BENCHIMOL, MARLENE; ORTEGA-LOPEZ, J. The iron-induced

cysteine proteinase TvCP4 plays a key role in Trichomonas vaginalis haemolysis. Microbes and Infection. , v.15, p.958 - 968, 2013.

6. DE ANDRADE ROSA, IVONE, DE SOUZA, WANDERLEY, BENCHIMOL, MARLENE High-resolution scanning electron

microscopy of the cytoskeleton of Tritrichomonas foetus. Journal of Structural Biology (Print). , v.183, p.412 - 418, 2013. *IN



120

7. ESDRAS-TEIXEIRA, D.; BENCHIMOL, M., RODRIGUES, J. C. F., CREPALDI, P. H., PIMENTA, P. P., DESOUZA, W. Atlas

didático-Ciclo de Vida da Leishmania. Rio de Janeiro : Fundação Cecierj, 2013, v.1. p.64. [BOOK] *IN COLLABORATION WITH

DE SOUZA (AL 9).

8. ESDRAS-TEIXEIRA, D.; BENCHIMOL, M.; RODRIGUES, J. C. F.; CREPALDI, P. H.; PIMENTA, P. F. DESOUZA, W. The Cell

Biology of Leishmania: How to Teach Using Animations. PLoS Pathogens. , v.9, p.e1003594 - , 2013. *IN COLLABORATION WITH

DE SOUZA (AL 9).

9. ROCHA D., DE ANDRADE ROSA, IVONE, SOUZA, W., BENCHIMOL, MARLENE. Evaluation of the effect of miltefosine on

Trichomonas vaginalis. Parasitology Research (1987. Print). , p.12 - , 2013. *IN COLLABORATION WITH DE SOUZA (AL 9).

10. ROSA, I., CARUSO, M. B., RODRIGUES, S. P., GERALDO, R. B., KIST, L. W., BOGO, M., GONZAGA, L., VASCONCELOS, A. T.

R., MORGADO, J. D., ZINGALI RB, BENCHIMOL, M. New insights in the Golgi complex of Tritrichomonas foetus. Parasitology

(Cambridge. Online). , v.18, p.1 - 13, 2013.

11. SOUZA, D. B.; COSTA, W.; CARDOSO, L. E. M.; BENCHIMOL, M.; SAMPAIO, M.; SAMPAIO, F. IBJU-747-12-Does prolonged

pneumoperitoneum affect the kidney? Oxidative stress, stereological and electron microscopy study in a rat model. International Braz J

Urol (Impresso). , v.39, p.30 - 36, 2013.

12. VILELA, R.; BENCHIMOL, M. “IL-10 release by bovine epithelial cells cultured with Trichomonas vaginalis and Tritrichomonas foetus.

Memórias do Instituto Oswaldo Cruz (Impresso). , v.107, p.1 - 9, 2013.


121

AL 13 - Associated Laboratory of Structural

Biothecnology

- Coodinator:

Celso B. Sant'Anna Filho - Instituto Nacional de Metrologia (INMETRO)

- Researchers from national institutions: Ana Paula Gadelha – INMETRO.

Danielle Pereira Cavalcanti – INMETRO.

Emile Santos Barrias – INMETRO.

Rafael de Cássio Bernardi – INMETRO.

Roberta Fernandes Pinto – INMETRO.


Ana Paula Gomes Braga de Azevedo. (INMETRO)

Nathalia Vieira Müller. (INMETRO)

Rafael Mesquita Stoque. (INMETRO)

Veronica da Silva Ferreria. (Unigranrio)

Yuri Komatsu Damas Abud. (Unigranrio)

Camila Silva Gonçalves (UFRJ)

Lissa Catherine Reignault de Souza Barros Moreira (UFRJ)


Chayenne Correia dos Santos (INMETRO)

Mateus Ferreira Conz Eugenio (Unigranrio)

Juliana Martins Marteleto Novo (UFRJ)

Thayane Rita de Farias (INMETRO)


Jessica de Araujo Paula (UFF)

João Vitor Mayrinck(Unigranrio)

Jualiana Alves (UFRJ)

The Structural Biology Laboratory, at

National Institute of Metrology, Quality

and Technology– INMETRO, has a group

composed by biologists and physicists. The

focus of our group is mainly based on

bionanometrological and biofuels studies.


results obtained during the four years’


2016):

Development of new nanosensors

Many portable instruments have been made

possible by the use of clever designs

incorporating smaller components and

miniature gratings for use in spectrometers.

Furthermore they take up less space in a

laboratory, many of them can work off

batteries, often cost less than conventional

benchtop instruments, require less sample

and reagents producing less waste, and are

often simpler to use. Also, low-cost

powerful microcontrollers are being

included as control-processing units in

many types of portable and hand-held

instrumentation. In 2015, we developed a

new microcontrolled photometer based on

lightemitting-diodes (LED) for detection of

Pb2+ using gold nanoparticles (AuNPs).

The photometer based on sensor TCS230


122

and an Arduino electronic card as

acquisition system was a simple and low-

cost assembly. These features may enable

the proposed approach to be used as a

stand-alone setup for Pb2+ determination in

water. In addition, we believe that this

approach may serve as a foundation for the

preparation of practical nanosensors for the

rapid determination of Pb2+ concentrations

in aqueous samples, having the features

required to become a field instrument.

Nanoparticles and antibiotics

Silver has long been known to prevent

antimicrobial activity, but the advent of

antibiotics has severely reduced its use for

bactericidal purposes. The ability of various

microorganisms to adapt to antimicrobial

drugs and the improper administration of

antibiotics have enabled emergence of

multi-drug-resistant pathogens, for which

treatment with broad-spectrum antibiotics is

less effective, more toxic, and expensive.

This has led to the renaissance of silver-

based bactericidal agents, especially in the

nanoregime, which display considerable

broad-spectrum antimicrobial activity. An

interesting approach is the combination of

nanoparticles and antibiotics to yield a

more potent antimicrobial agent.

In this context, we combined silver

nanoparticles (AgNPs) with doxycycline

(DO), an antibiotic from the class of

tetracyclines, to evaluate the potentiality of

this hybrid as a bactericidal agent against E.

coli. Polyvinylpyrrolidone (PVP) was used

as a stabilizer to prevent the excessive

growth and agglomeration of AgNPs.

Interestingly, DO bound directly to PVP

and had its concentration increased around

the particle as a consequence of this

interaction. As a result, the AgNPs/DO

conjugates presented enhanced bactericidal

properties compared to the individual

components (Figure 1). Stabilizing agents

are generally unwanted on the surfaces of

nanoparticles because of their potential to

block adsorption surface sites. However, we

have shown that PVP played a paramount

role in concentrating DO around the

particle, which culminated in an increased

bactericidal activity towards E. coli.

Figure 1. TEM images with respective size distributions of PVP and Ag+ on UV-vis spectra of the AgNPs


123

Also, the biogenic (“green”) synthesis of

AgCl-NPs can be performed in

physiological conditions of pH, temperature

and pressure, is eco-friendly and

comparatively inexpensive; thus, green

synthesis is preferable to physical/chemical

4 methods for AgCl-NP production for

biomedical purposes. We investigated the

biosynthesis of AgCl-NPs by conditioned

medium from cultures of the commercially

valuable green microalgae Chlorella

vulgaris, which has been extensively used

in industrial applications and food products.

The composition, structure and morphology

of AgCl-NPs were characterized by a

variety of spectroscopic and electron

microscopy approaches. In addition, we

investigated the antimicrobial activity of C.

vulgaris-derived AgCl-NPs against Gram-

positive (Staphylococcus aureus) and

Gram-negative (Klebsiella pneumonia)

bacteria (Figure 2). Our findings strongly

indicated that the AgCl-NPs from C.

vulgaris conditioned medium is a promising

‘green’ alternative for biomedical

application as antimicrobials.

Figure 2. – Ultrastructural analysis of Staphylococcus aureus and Klebsiella pneumoniae treated with AgCl-

NPs. Ultrathin transmission electron microscopy (TEM) sections of untreated S. aureus (Fig. 2A) and K.

pneumoniae (Fig. 2D) cells, showing the typical cell morphology of these pathogens, with electron-dense

cytoplasmic material homogeneously distributed. Ultrathin section of S. aureus (Fig. 2B, C) and K.

pneumoniae (Fig. 2E, F) cells treated with IC50 concentrations (157 and 247μg/mL, for S. aureus and K.

pneumoniae, respectively) of purified AgCl-NPs, showing the loss of chromosomal DNA (asterisks), generating

an cytoplasmic electronlucent area. Big arrows in Fig. 2B, C (S. aureus) and Fig. 2 E, F (K. pneumoniae)

indicate filamentous structures likely corresponding to stretched DNA fibers and small arrows indicate the

interaction of AgCl-NPs with bacterial surface. Fig. 2C and Fig. 2F show the accumulation of AgCl-NPs inside

the treated Staphylococcus aureus and Klebsiella pneumonia, respectively.

HCA into screening for biodiesel

production

Biodiesel from oleaginous microorganisms

is a viable substitute for a fossil fuel.

Current methods for microorganism lipid

productivity evaluation do not analyze lipid

dynamics in single cells. Here, we

described a high-content image analysis

(HCA) as a promising strategy for

screening oleaginous microorganisms for

biodiesel production, while generating

single-cell lipid dynamics data in large cell

density. Rhodotorula slooffliae yeast were

grown in standard (CTL) or lipid trigger

medium (LTM), and lipid droplet (LD)

accumulation was analyzed in deconvolved

confocal microscopy images of cells stained

with the lipophilic fluorescent Nile red

(NR) dye using automated cell and LD

segmentation. The ‘vesicle segmentation’

method yielded valid morphometric results

for limited lipid accumulation in smaller

LDs (CTL samples) and for high lipid

accumulation in larger LDs (LTM

samples)(Figure 3), and detected LD

localization changes (Figure 4). Thus, HCA

can be used to analyze the lipid

accumulation patterns likely to be

encountered in screens for biodiesel

production.


124

Figure 3. Representation of the total lipid volume relative to the cell body volume in Rhodotorula slooffiae

yeast cells as calculated from automated images analysis. Images represent mean cell body volume (CB, black

spheres) and mean lipid volume (L, grey spheres) values per cell, after growth for 3, 6 and 10 days in control

(CTL) or lipid trigger medium (LTM). L values were calculated as the mean volume of individual LDs

multiplied by the mean number of LDs per cell. All values were calculated based on automated imaging using

the vesicle segmentation method. The graphical representation was constructed by plotting the mean value

data of the measured total LD and cell body volume.

Figure 4. Proportion of lipid droplets (LDs) in the center of the cell compared with the periphery. A – Low

(left) and high (right) magnification images of Rhodotorula slooffiae yeast cells cultured for 3 days in ‘lipid

trigger’ medium (LTM), and then subjected to segmentation of lipid droplets (LDs) (green) located within

center of the cell (red) and cell body (purple) 28 boundaries. The ‘center of the cell’ mask was defined using

the same vesicle segmentation method used for the cell body segmentation, but with a more stringent post-

processing erosion parameter (Kernel size = 19, rather than the size 3 used for cell body segmentation). B - LD

counts in the cell body and ‘center of the cell’ segmented regions were performed in CTL and LTM images by

automated image analysis, and LDs whose 100% of the drop contour was located in the center of the cell's

mask. The proportion of LDs situated in the periphery of the cell was calculated by subtracting the number of

LDs in the center of the cell from the total number of LDs in the cell body.


125


1. ARAUJO JUNIOR, R. F. ; ARAUJO, A. A. ; PESSOA, J. B. ; FREIRE NETO, F. P. ; SILVA, G. R. ; OLIVEIRA, A. L. C. L. ;

CARVALHO, T. G. ; SILVAF, H. F. ; EUGÊNIO, MATEUS ; SANT'ANNA, C. ; GASPAROTTO, L. H. S. . Anti-inflammatory,

analgesic and anti-tumor properties of gold nanoparticles. Pharmacological Reports, v. 69, p. 119-129, 2016.

http://dx.doi.org/10.1016/j.pharep.2016.09.017

2. BRIENZO, Michel ; ABUD, YURI ; FERREIRA, SOLANGE ; CORRALES, ROBERTA C.N.R ; FERREIRA-LEITÃO, VIRIDIANA S.

; SOUZA, WANDERLEY DE *; SANT'ANNA, C. . Characterization of anatomy, lignin distribution, and response to pretreatments of

sugarcane culm node and internode. Industrial Crops and Products (Print), v. 84, p. 305-313, 2016. *IN COLLABORATION WITH DE

SOUZA (AL 9). http://dx.doi.org/10.1016/j.indcrop.2016.01.039

3. CAPUS, A. ; MONNERAT, M. ; RIBEIRO, L. C. ; DE SOUZA, WANDERLEY* ; SANT'ANNA, CELSO . Application of high-content

image analysis for quantitatively estimating lipid accumulation in oleaginous yeasts with potential for use in biodiesel production.

Bioresource Technology, v. 203, p. 309-317, 2016 *IN COLLABORATION WITH DE SOUZA (AL 9).


4. CEOTTO-VIGODER, H. ; MARQUES, S. L. S. ; SANTOS, I. N. S. ; ALVES, M. D. B. ; BARRIAS, E. S. ; ALVIANO, D. S. ;

BASTOS, M. C. F. . Nisin and lysostaphin activity against pre-formed biofilm of Staphylococcus aureus involved in bovine mastitis.

Journal of Applied Microbiology (Print), v. n/a, p. n/a-n/a, 2016. http://dx.doi.org/10.1111/jam.13136

5. DE S. ARAÚJO, GLAUBER R. ; FONTES, GISELLE N. ; LEÃO, DANIELA ; ROCHA, GUSTAVO MIRANDA ; PONTES, BRUNO ;

SANT’ANNA, CELSO ; DE SOUZA, WANDERLEY *; FRASES, SUSANA . Cryptococcus neoformans capsular polysaccharides form

branched and complex filamentous networks viewed by high-resolution microscopy. Journal of Structural Biology (Print), v. 193, p. 75-

82, 2016. *IN COLLABORATION WITH DE SOUZA (AL 9). http://dx.doi.org/10.1016/j.jsb.2015.11.010

6. EUGÊNIO, MATEUS ; MULLER, NATHALIA ; FRASÉS, SUSANA ; PAES, RODRIGO ; MAURÍCIO, LUIZ ; LEMGRUBER,

LEANDRO ; FARINA, MARCOS ; DE SOUZA, WANDERLEY* ; SANT'ANNA, CELSO . Yeast-derived biosynthesis of silver/silver

chloride nanoparticles and their antiproliferative activity against bacteria. RSC Advances: an international journal to further the chemical

sciences, v. 6, p. 9893-9904, 2016. *IN COLLABORATION WITH DE SOUZA (AL 9). http://dx.doi.org/10.1039/c5ra22727e

7. FERREIRA, V. S. ; CELSO SANT'ANNA . The effect of physicochemical conditions and nutrient sources on maximizing the growth and

lipid productivity of green microalgae. PHYCOLOGICAL RESEARCH, v. 65, p. 3-13, 2016. http://dx.doi.org/10.1111/pre.12160

8. FERREIRA, V. S. ; EUGÊNIO, MATEUS ; LIMA, L. M. T. R. E. ; FRASÉS, S. ; SOUZA, WANDERLEY DE* ; SANT?ANNA,

CELSO . Green production of microalgae-based silver chloride nanoparticles with antimicrobial activity against pathogenic bacteria.

Enzyme and Microbial Technology, v. 97, p. 114-121, 2016. *IN COLLABORATION WITH DE SOUZA (AL 9).


9. MATADAMAS-MARTÍNEZ, FÉLIX ; CASTILLO, RAFAEL ; HERNÁNDEZ-CAMPOS, ALICIA ; MÉNDEZ-CUESTA, CARLOS ;

DE SOUZA, WANDERLEY* ; Gadelha, Ana Paula ; NOGUEDA-TORRES, BENJAMÍN ; HERNÁNDEZ, JOSÉ MANUEL ; YÉPEZ-

MULIA, LILIÁN . Proteomic and ultrastructural analysis of the effect of a new nitazoxanide-N-methyl-1H-benzimidazole hybrid against

Giardia intestinalis. Research in Veterinary Science, v. 105, p. 171-179, 2016. *IN COLLABORATION WITH DE SOUZA (AL 9).

http://dx.doi.org/10.1016/j.rvsc.2016.02.006


1. AH, I. ; ROJAS, R. L. G. ; MANTILLA, B. S. ; SANT'ANNA, C. ; PRAL, E. M. F. ; SILBER, A. M. . The Uptake of GABA in

Trypanosoma cruzi. The Journal of Eukaryotic Microbiology, v. 62, p. 629-636, 2015. http://dx.doi.org/10.1111/jeu.12219

2. BRAGA, R ; ALMEIDA, L ; GUERREIRO, LH ; TINOCO, P ; MIRANDA, KR ; BRAGA, C ; GADELHA, AP ; GARCIA, S ; LIMA,

LMTR . Molecular confinement of human amylin in lipidic nanoparticles. Journal of Liposome Research, v. 4, p. 1-11, 2015.

https://doi.org/10.3109/08982104.2015.1076462

3. DE CARVALHO, TECIA M. U. ; BARRIAS, EMILE S. ; DE SOUZA, WANDERLEY* . Macropinocytosis: a pathway to protozoan

infection. Frontiers in Physiology, v. 6, p. 106, 2015. http://dx.doi.org/10.3389/fphys.2015.00106 *IN COLLABORATION WITH DE

SOUZA (AL 9)

4. FERREIRA, VERONICA ; PINTO, ROBERTA FERNANDES ; SANT'ANNA, CELSO . Low light intensity and nitrogen starvation

modulate the chlorophyll content of Scenedesmus dimorphus. Journal of Applied Microbiology (Print), v. 120, p. n/a-n/a, 2015.

http://dx.doi.org/10.1111/jam.13007

5. GADELHA, ANA PAULA ROCHA; BENCHIMOL, MARLENE* ; DE SOUZA, WANDERLEY* . Helium ion microscopy and

ultra-high-resolution scanning electron microscopy analysis of membrane-extracted cells reveals novel characteristics of the cytoskeleton

of Giardia intestinalis. Journal of Structural Biology (Print), v. 190, p. 271-278, 2015. *IN COLLABORATION WITH DE SOUZA

(AL 9) AND BENCHIMOL (AL 12) http://dx.doi.org/10.1016/j.jsb.2015.04.017

6. LEMGRUBER , LEANDRO ; SANT'ANNA, C. ; GRIFFTH, C. ; ABUB, Y. ; MHLANGA, M. ; WALLICH, R. ; FRISCHKNECHT, F. .

Nanoscopic Localization of Surface-Exposed Antigens of Borrelia burgdorferi. Microscopy and Microanalysis (Print), v. 21, p. 680-688,

2015. http://dx.doi.org/10.1017/s1431927615000318

7. MORAIS, C. ; CARVALHO, J. ; NASCIMENTO, P. ; SANT'ANNA, CELSO ; EUGÊNIO, MATEUS ; GASPAROTTO, LUIZ H.S. ;

LIMA, C. . A low-cost microcontrolled photometer with one color recognition sensor for selective detection of Pb2+ using gold

nanoparticles. Analytical Methods (Print), v. 7, p. 7917-7922, 2015. http://dx.doi.org/10.1039/c5ay01762a

8. SILVA, HELOIZA F ; DE LIMA, K. M. G. ; CARDOSO, MATEUS BORBA ; DE OLIVEIRA, JESSICA FERNANDA AFFONSO ;

MELO, MARIA ; SANT’ANNA, CELSO ; EUGÊNIO, MATEUS ; GASPAROTTO, LUIZ H.S. . Doxycycline conjugated with

polyvinylpyrrolidone-encapsulated silver nanoparticles: a polymer?s malevolent touch against Escherichia coli. RSC Advances: an

international journal to further the chemical sciences, v. 5, p. 66886-66893, 2015. http://dx.doi.org/10.1039/c5ra10880b


1. BRIENZO, MICHEL ; FERREIRA, SOLANGE ; VICENTIM, MARCOS P. ; DE SOUZA, WANDERLEY* ; SANT’ . Comparison

Study on the Biomass Recalcitrance of Different Tissue Fractions of Sugarcane Culm. BioEnergy Research, v. 7, p. 1454-1465, 2014. *IN

COLLABORATION WITH DE SOUZA (AL 9). http://dx.doi.org/10.1007/s12155-014-9487-8

2. REIGNAULT, LISSA CATHERINE ; BARRIAS, EMILE SANTOS ; SOARES MEDEIROS, LIA CAROLINA ; DE SOUZA,

WANDERLEY* ; DE CARVALHO, TECIA MARIA ULISSES . Structures containing galectin-3 are recruited to the parasitophorous

vacuole containing Trypanosoma cruzi in mouse peritoneal macrophages. Parasitology Research (1987. Print), v. 113, p. 2323-2333, 2014.

*IN COLLABORATION WITH DE SOUZA (AL 9) http://dx.doi.org/10.1007/s00436-014-3887-8

3. ROCHA, G. M. ; CAVALCANTI, D. P. ; DE SOUZA, W. . Avances de la tecnología en microscopía de fuerza atómica: nuevas

posibilidades para analizar la organización estructural de los protozoos patógenos. In: Luis Germán Rodríguez L.. (Org.). las TIC en el

combate de las enfermedades desatendidas: una visión latinoamericana. 1ed.Barcelona- Espanha: Editorial Ariel, S.A, 2014, v. 1, p. 123-

135. IN COLLABORATION WITH DE SOUZA (AL 9) - [BOOK CHAPTER].

http://dx.doi.org/10.1016/j.pharep.2016.09.017

http://dx.doi.org/10.1016/j.indcrop.2016.01.039




http://dx.doi.org/10.1039/c5ra22727e

http://dx.doi.org/10.1111/pre.12160


http://dx.doi.org/10.1016/j.rvsc.2016.02.006

http://dx.doi.org/10.1111/jeu.12219

https://doi.org/10.3109/08982104.2015.1076462

http://dx.doi.org/10.3389/fphys.2015.00106



http://dx.doi.org/10.1017/s1431927615000318

http://dx.doi.org/10.1039/c5ay01762a

http://dx.doi.org/10.1039/c5ra10880b

http://dx.doi.org/10.1007/s12155-014-9487-8

http://dx.doi.org/10.1007/s00436-014-3887-8


126

4. SANT'ANNA, C.; FERREIRA, V. S. ; MONNERAT, M. M. ; PINTO, R. F. ; SOUZA, WANDERLEY DE* ; MARTINS, J. L. .

Microscopy approaches to screening oleaginous microorganisms and evaluating their potential as feedstock for biodiesel production. In:

A. Méndez-Vilas. (Org.). Microscopy approaches to screening oleaginous microorganisms and evaluating their potential as feedstock for

biodiesel production. 13ed.: Formatex Research Center, 2014, v. 1, p. 484-491. *IN COLLABORATION WITH DE SOUZA (AL 9) -

[BOOK CHAPTER].

5. SANT'ANNA, C.; SOUZA, WANDERLEY DE ; BRIENZO, M. . The influence of the heterogeneity, physicochemical and structural

properties on the recalcitrance and conversion of sugarcane bagasse. In: Eleanore Webb. (Org.). The influence of the heterogeneity,

physicochemical and structural properties on the recalcitrance and conversion of sugarcane bagasse. 1ed.Nova Iorque: Nova Science

Publisher, Inc, 2014, v. 1, p. 1-33. *IN COLLABORATION WITH DE SOUZA (AL 9) - [BOOK CHAPTER]

6. ZUMA, ALINE ARAUJO ; CAVALCANTI, DANIELLE PEREIRA ; ZOGOVICH, MARCELO ; MACHADO, ANA CAROLINA

LOYOLA ; MENDES, ISABELA CECÍLIA ; THIRY, MARC ; GALINA, ANTONIO ; DE SOUZA, WANDERLEY* ; MACHADO,

CARLOS RENATO ; MOTTA, MARIA CRISTINA MACHADO . Unveiling the effects of berenil, a DNA-binding drug, on

Trypanosoma cruzi: implications for kDNA ultrastructure and replication. Parasitology Research (1987. Print), v. Oct, p. 1-12, 2014. *IN

COLLABORATION WITH DE SOUZA (AL 9) http://dx.doi.org/10.1007/s00436-014-4199-8


1. ABUB, Y. ; COSTA, L. ; SOUZA, WANDERLEY DE* ; SANT'ANNA, CELSO . Revealing the microfibrillar arrangement of the cell

wall surface and the macromolecular effects of thermochemical pretreatment in sugarcane by atomic force microscopy. Industrial Crops

and Products (Print), v. 51, p. 62-69, 2013. *IN COLLABORATION WITH DE SOUZA (AL 9).


2. BARRIAS, EMILE SANTOS; DE CARVALHO, TECIA MARIA ULISSES ; DE SOUZA, WANDERLEY* . TRYPANOSOMA

CRUZI: ENTRY INTO MAMMALIAN HOST CELLS AND PARASITOPHOROUS VACUOLE FORMATION. FRONTIERS IN

IMMUNOLOGY (ONLINE), V. 4, P. 10.3389/FIMMU.2, 2013. IN COLLABORATION WITH DE SOUZA (AL 9)

HTTP://DX.DOI.ORG/10.3389/FIMMU.2013.00186

3. CAVALCANTI, DANIELLE PEREIRA; GONÇALVES,D.L. ; PEDROSA, BR ; ZOGOVICH, M ; COSTA, L.T. . DNA preparation for

AFM imaging in air: differences in physical parameters. Atomic Force Microscopy (AFM): Principles, Modes of Operation and

Limitations. 1ed.: , 2013, v. , p. 1-10. [BOOK CHAPTER].

4. GADELHA, ANA PAULA ROCHA; CUNHA-E-SILVA, NARCISA LEAL ; DE SOUZA, WANDERLEY* Assembly of the

Leishmania amazonensis flagellum during cell differentiation. Journal of Structural Biology (Print), v. 184, p. 280-292, 2013. *IN

COLLABORATION WITH DE SOUZA (AL 9) http://dx.doi.org/10.1016/j.jsb.2013.09.006

5. MAIA-BRIGAGÃO, CLAUDIA ; GADELHA, ANA PAULA ROCHA ; DE SOUZA, WANDERLEY* . New Associated Structures of

the Anterior Flagella of Giardia duodenalis. Microscopy and Microanalysis (Print), v. 19, p. 1374-1376, 2013. *IN COLLABORATION

WITH DE SOUZA (AL 9) http://dx.doi.org/10.1017/s1431927613013275

6. MELLO, T.M. ; CAVALCANTI, D. P. ; ZOGOVICH, M ; DE SOUZA, W*. ; MOTTA, M. C. M. . Acriflavine treatment promotes

dyskinetoplasty in Trypanosoma cruzi as revealed by ultrastructural analysis. Parasitology (London. Print), v. 140, p. 1422-1431, 2013.

*IN COLLABORATION WITH DE SOUZA (AL 9) http://dx.doi.org/10.1017/s0031182013001029

7. REIS, V. M. ; OLIVEIRA, L. S. ; PASSOS, R. M. F. ; VIANA, N. B. ; MERMELSTEIN, C. ; SANT'ANNA, C. ; PEREIRA, R. C. ;

PARADAS, W. C. ; THOMPSON, F. L. ; AMADO-FILHO, G. M. ; SALGADO, L. T. . Traffic of Secondary Metabolites to Cell Surface

in the Red Alga Laurencia dendroidea Depends on a Two-Step Transport by the Cytoskeleton. Plos One, v. 8, p. e63929, 2013.


8. SANT'ANNA, C.; COSTA, L. ; ABUB, Y. ; BIANCATTO, L. ; MIGUENS, F. ; SOUZA, WANDERLEY DE* . Sugarcane cell wall

structure and lignin distribution investigated by confocal and electron microscopy. Microscopy Research and Technique (Print), v. 76, p.

829-834, 2013. *IN COLLABORATION WITH DE SOUZA (AL 9).http://dx.doi.org/10.1002/jemt.22235

http://dx.doi.org/10.1007/s00436-014-4199-8


http://dx.doi.org/10.3389/fimmu.2013.00186


http://dx.doi.org/10.1017/s1431927613013275

http://dx.doi.org/10.1017/s0031182013001029


http://dx.doi.org/10.1002/jemt.22235


127

AL 14 - Associate Laboratory of Structural Biology

- Coordinator:

Edilene Oliveira da Silva – UFPA.


Ana Paula Drummond Rodrigues –INSTITUTO EVANDRO CHAGAS (IEC)


Alexandre Escher Boger – ICB/UPA

Amanda Anastácia Pinto Hage ICB/UFPA

Bruno José Martins da Silva ICB/UFPA

Davi Marcos Souza de Oliveira ICB/UFPA

Jorge Augusto Leão Pereira ICB/UFPA

Josineide Pantoja da Costa ICB/UFPA

Lienne Silveira de Moraes ICB/UFPA

Luis Henrique Seabra de Farias ICB/UFPA


Celice Shirley Alvares Xavier


Dara da Costa Soares ICB/UFPA,

Vanessa Ingrid Cardoso Pereira ICB/UFPA

Letícia Cristina Dalzy Castro ICB/UFPA

Ingrid Melo Rocha ICB/UFPA

Sandro Wilson Gomes Pereira ICB/UFPA

- Technicians:

Heyder Coutinho Almeida

Fernanda Lobo Brasil

"Considering the geographic and scientific isolation of the LA 14, INBEB's support favored a

technical-scientific advance, representing a qualitative and quantitative leap in personnel

training and publications in journals of international circulation. In addition, it favored an

expressive participation of the LA 14 members in activities of education and dissemination of

science in the basic education of students from poor municipalities of the Amazon region. "

- Professor Edilene Oliveira da Silva.

Bioproducts as microbicidal agent source

and immunomodulatory activity.

Our research focuses on the development of

new strategies for treatment of different

infectious diseases based on bioproducts

from Amazon's biodiversity. Natural

products from plants, microorganisms and

animals represent an important alternative

source of new microbicidal agents. Our

research is focused on the treatment of

leishmaniasis and fungal infections, which

the chemotherapy is the only effective

treatment for these diseases. Besides being

expensive, the drugs used are in general

toxic and require long-term treatment.

Leishmania is an intracellular parasite of

macrophages, and is responsible for over 12

million leishmaniasis cases in more than 98

countries. Depending on the species, the

protozoan can promote different clinical

manifestations that are associated with

cutaneous and visceral pathologies.

Leishmania (L.) amazonensis is an

important agent that induces cutaneous


128

leishmaniasis and is responsible for the

inhibition of the immune system, which

promotes a high rate of parasite

proliferation.

The filamentous fungus Curvularia

pallescens is an entophytic fungi and

melanin producer that occasionally causes a

variety of human infections. Nowadays, the

effectiveness of bioproducts on pathogenic

fungi has been widely studied. Melanin is

an important virulence factor and the use of

melanogenesis inhibitors can be used as a

potential antifungal drug representing a new

pharmacological target. Kojic acid (KA), a

secondary metabolite synthesized by

Aspergillus fungi, has several applications,

including fungistatic activity and it

synergistically activity with conventional

antifungal drugs (amphotericin B). This

substance is a specific inhibitor of the

enzyme tyrosinase, which is involved in

melanin synthesis. Thus, KA showed

fungistatic action upon Curvularia

pallescens fungi and promoted significant

changes in cell morphology and decreased

cell viability (Figure 1).

Figure 1: Transmission eletron microscopy of Curvularia pallescens, treated with differents concentration of

AK. (A) control without treatment. (B-E) treated with 25, 50, 100 e 200 µg/mL of AK, respectively. Note

fibrillar structure disruption of the cell wall (long arrows B-E), compared with the control. Scale bar 2 µm.


129

These results suggested that KA had

fungistatic activity. Additionally, KA also

promoted an immunomodulatory effect on

murine bone marrow cells, human

monocytes and human neutrophils (Figure

2), stimulating cell differentiation and

activation through morphological changes.

This next step will be developed an AK

topical formulation in non-human primates

infected with Leishmania (L.) amazonensis.

Figure 2: Morphological analysis of neutrophils treated with KA (50 µg/mL) for one hour. (A-C) Light

microscopy. (A) Untreated cells. (B) Neutrophils activated with 100 nM PMA. Note the presence of

cytoplasmic projections and vacuoles. (C) Neutrophil treated with KA, observe pseudopod extension, high

spreading ability and increase of cell volume. Bars: 10 µM. (D-F) The morphological analysis by scanning

electron microscopy. (D) Control cells with typical morphology. (E) Neutrophils treated with 100 nM PMA. (F)

Neutrophils treated with 50 µg/mL KA. Treated cells showed pseudopod extension and increase of cell volume.

Bars: 15 µm.

Other bioproduct analyzed is the aqueous

extract of Physalis angulata (AEPa), which

promotes the differentiation of bone

marrow cells into macrophages, activation

of macrophage through the production of

superoxide anions and has antileishmanial

properties. The group also has studied the

activity of (+)-phyllanthidine, an alkaloid

obtained from Margaritaria nobilis. This

alkaloid presents effects against

promastigotes (Figure 3) and amastigotes

forms from Leishmania amazonensis.


130

Figure 3: Effect of (+)-Phyllanthidine on ultrastructure of promastigotes of Leishmania (L.) amazonensis,

observed by scanning (A, C and E) and transmission (B, D and F) electron microscopy. MEV (A) Control

promastigote form without treatment; (C) Promastigote treated with 50µg/mL, showing septation of the cell

body and shortening of the flagellum (arrows); (E) Promastigote treated with 100µg/mL, observe cellular

debris and formation of rosettes. MET (B) Control without treatment, showing the characteristic structure of

kinetoplastids; (D) Promastigote forms treated with 50 µg/mL of alkaloid. Note swelling of the kinetoplast; (D)

Increased the number of acidocalcisomes (asteristics). N – nucleus; FP– flagelar pocket; K – kinetolast; F –

flagellum; M – Mitochondria (*) acidocalcisomes. Scale bars 1µm.


131

In addition, our group has studied the

action of Crotoxin, a toxin derived from

Crotalus durissus terrificus snake venom,

during the infection of L. amazonensis.

Animal venoms and their purified

compounds are known to exhibit a variety

of pharmacological activities, including

activities against pathogens. Crotoxin is the

main component of C. durissus terrificus

venom, and it has several biological effects.

Nevertheless, there is no report of crotoxin

activity during macrophage - Leishmania

interactions. It was observed that CTX

inhibited parasite growth (Figure 4) and

also acted as a modulator of the immune

response during infection of macrophages

(Figure 5). These results demonstrated that

bioproducts effectively inhibits the growth

of pathogens, present immunomodulatory

activity and does not have cytotoxic effects

on the host cells.

Fig. 4 – Macrophages were infected with L. amazonensis and treated with Crotoxin (CTX) for 24 hours (A)

and 48 hours (B). A1: The phagocytic index of host cells that were treated with CTX for 24 hours. Note the

significant increase in phagocytosis after treatment with 2.4 µg/mL of CTX. A2 and A3: Giemsa staining of

macrophages that were infected (CTL) and or infected and treated with 2.4 µg/mL of CTX, respectively. Note

the higher amount of amastigotes inside the macrophages (large arrows). B1 The phagocytic index of host cells

that were treated with CTX for 48 hours. B2 and B3: Giemsa staining of macrophages that were infected

(CTL) or infected and treated with 2.4 µg/mL of CTX, respectively. **p<0.01.


132

Fig. 5 – Cytokine concentrations in macrophage that were infected with Leishmania and treated with CTX.

Treated and infected macrophages produced a higher concentration of IL-6 (A) and TNF-α (B) compared to

the untreated controls. *p< 0.05.

AL14 publications in 2016: 1. DA SILVA, BJM ; SILVA, R.R.P. ; RODRIGUES, A.P.D. ; FARIAS, L. H. S. DE ; DO NASCIMENTO, JOSE LUIZ ; SILVA, E. O.

Physalis angulata induces death of promastigotes and amastigotes of Leishmania (Leishmania) amazonensis via the generation of reactive

oxygen species. Micron (Oxford. 1993), v. 2016, p. 25-32, 2016. doi: 10.1016/j.micron.2015

2. DE OLIVEIRA, DAVI MARCOS SOUZA ; MARTINS DA SILVA, BRUNO JOSÉ ; DE SENA, CHUBERT BERNARDO CASTRO ;

LIMA, JOSÉ APRÍGIO NUNES ; VASCONCELOS DOS SANTOS, THIAGO ; SILVEIRA, FERNANDO TOBIAS ; SILVA, EDILENE

OLIVEIRA . Comparative analysis of carbohydrate residues in the midgut of phlebotomines (Diptera: Psychodidae) from colony and field

populations from Amazon, Brazil. Experimental Parasitology, v. 168, p. 31-38, 2016. http://dx.doi.org/10.1016/j.exppara.2016.06.002

AL14 publications in 2015: 1. DA SILVA, RAQUEL RAICK P. ; DA SILVA, BRUNO J. M. ; RODRIGUES, ANA PAULA D. ; FARIAS, LUIS HENRIQUE S. ; DA

SILVA, MILTON N. ; ALVES, DANILA TERESA V. ; BASTOS, GILMARA N. T. ; DO NASCIMENTO, JOSÉ LUIZ M. ; SILVA,

EDILENE O. In vitro biological action of aqueous extract from roots of Physalis angulata against Leishmania (Leishmania) amazonensis.

BMC Complementary and Alternative Medicine (Online), v. 15, p. 249, 2015. Doi: 10.1186/s12906-015-0717-1.

2. MORAES, L.S. ; DONZA, M. ; RODRIGUES, ANA PAULA DRUMMOND ; DA SILVA, BJM ; DAVI S. B. BRASIL ; ZOGHBI, M.

G. ; ANDRADE, E. ; GUILHON, G. M. ; SILVA, E. O. Leishmanicidal Activity of (+) - Phyllanthidine and the Phytochemical profile of

Margaritaria nobilis (Phyllanthaceae). Molecules (Basel. Online), v. 20, p. 22157-22169, 2015. doi: 10.3390/molecules201219829.

AL14 publications in 2014: 1. DA SILVA, BRUNO JOSÉ MARTINS; RODRIGUES, ANA PAULA D.; FARIAS, LUIS HENRIQUE S.; HAGE, AMANDA

ANASTÁCIA P.; DO NASCIMENTO, JOSE LUIZ M.; SILVA, EDILENE O. Physalys angulata induces in vitro differentiation of

murine bone marrow cells into macrophages. BMC Cell Biology 15:37, 2014 Qualis B1. doi: 10.1186/1471-2121-15-37.

2. LIMA, CARLYLE RIBEIRO; SILVA, JOSÉ ROGÉRIO A.; CARDOSO, ÉRICA DE TÁSSIA CARVALHO; SILVA, EDILENE O.;

LAMEIRA, JERÔNIMO; DO NASCIMENTO, JOSÉ LUIZ MARTINS; BRASIL, DAVI DO SOCORRO BARROS AND ALVES,

CLÁUDIO N. Combined Kinetic Studies and Computational Analysis on Kojic Acid Analogous as Tyrosinase Inhibitors. Molecules 19,

9591-9605, 2014 Qualis B1. doi: 10.3390/molecules19079591.

3. RODRIGUES, ANA PAULA D. ; FARIAS, LUIS HENRIQUE S. ; CARVALHO, ANTONIO SÉRGIO C.; SANTOS, ALBERDAN S. ;

DO NASCIMENTO, JOSÉ LUIZ M. ; SILVA, EDILENE O. A Novel Function for Kojic Acid, a Secondary Metabolite from Aspergillus

Fungi, as Antileishmanial Agent. Plos One 9, p. e91259, 2014 Qualis A2. Doi: 10.1371/journal.pone.0091259.

AL14 publications in 2013: 1. FARIAS, LUIS HENRIQUE S. RODRIGUES, ANA PAULA D.; SILVEIRA, FERNANDO T.; SEABRA, SÉRGIO H.; DAMATTA,

RENATO A.; SARAIVA, ELVIRA M. AND SILVA, EDILENE O. Phosphatidylserine Exposure and Surface Sugars in Two Leishmania

(Viannia) braziliensis Strains Involved in Cutaneous and Mucocutaneous Leishmaniasis. Revista: The Journal of Infectious Diseases

207:537-543, 2013 Qualis A1. doi: 10.1093/infdis/jis689.








133

AL 15 - Associated Laboratory of Microscopy CETENE

- Coodinator:

Christina Alves Peixoto - Fundação Oswaldo Cruz

- Researchers from national institutions: Ana Célia Oliveira Santos – UFPE.


Maria Eduarda Rocha de França (UFPE)

Wilma Helena de Oliveira (UFPE)

Laise Aline Martins dos Santos (Fiocruz)

José Luiz de Oliveira Magalhães (UFPE)

Gabriel Barros Rodrigues (UFPE)

Deniele Bezerra Lós (UFPE)

José Luiz de Oliveira Magalhães (UFPE)


Rodrigo Barros Ramos (UFPE)

Amanda Costa Oliveira (UFPE)


Eduardo Pereira Duarte da Silva (UFPE)

This report will focus mainly on the two

years (2013 and 2014) that the AL 15

received funding from INBEB:

anti-inflammatory activity of

Diethylcarbamazine

Diethylcarbamazine (DEC) is an antifilarial

drug with potent anti-inflammatory

properties as a result of its interference with

the metabolism of arachidonic acid. The

aim of the present study was to evaluate the

anti-inflammatory activity of DEC in a

mouse model of acute inflammation

(carrageenan-induced pleurisy). The

injection of carrageenan into the pleural

cavity induced the accumulation of fluid

containing a large number of

polymorphonuclear cells (PMNs) as well as

infiltration of PMNs in lung tissues (Figure

1) and increased production of nitrite and

tumor necrosis factor-α and increased

expression of interleukin-1β,

cyclooxygenase (COX-2), and inducible

nitric oxide synthase. Carrageenan also

induced the expression of nuclear factor-

κB. The oral administration of DEC

(50 mg/Kg) three days prior to the

carrageenan challenge led to a significant

reduction in all inflammation markers. The

present findings demonstrate that DEC is a

potential drug for the treatment of acute

lung inflammation (Ribeiro et. al.,

Mediators of Inflammation, 2014).

a)

b)

c) Figure 1: Ultrastructural analysis of lung after

carrageenan-induced injury and DEC treatment;

(a) and (b) lung sections from mice with

carrageenan-induced pleurisy showing enhanced

thickness of the interstitial space filled with

collagen fibers (thin arrows), myelin bodies

(arrowheads), vacuoles (asterisks), and lamellar

bodies containing electrodense granules (short

arrows); (c) lung treated with DEC presenting

preserved pneumocytes; bar = 2000 nm.


134

This study investigated the anti-

inflammatory effects of DEC on the CCl4-

induced hepatotoxicity in C57BL/6 mice.

Chronic inflammation was induced by i.p.

administration of CCl4 0.5 μL/g of body

weight through two injections a week for 6

weeks. DEC (50 mg/kg) was administered

by gavage for 12 days before finishing the

CCl4 induction. Histological analyses of

the DEC-treated group exhibited reduced

inflammatory process and prevented liver

necrosis and fibrosis. Immunohistochemical

and immunofluorescence analyses of the

DEC-treated group showed reduced COX-

2, IL1, MDA, TGF-, and SMA

immunopositivity, besides exhibiting

decreased IL1, COX-2, NFB, IFN, and

TGF expressions in the western blot

analysis. The DEC group enhanced

significantly the IL-10 expression. The

reduction of hepatic injury in the DEC-

treated group was confirmed by the COX-2

and iNOS mRNA expression levels. Based

on the results of the present study, DEC can

be used as a potential anti-inflammatory

drug for chronic hepatic inflammation

(Rocha et. al., Mediators of Inflammation,

2014).

We also reported the effects of DEC

pretreatment on NF-κB regulation using the

pleurisy model induced by carrageenan.

Swiss male mice (Mus musculus) were

divided into four experimental groups:

control (SAL); carrageenan (CAR);

diethylcarbamazine (DEC) and curcumin

(CUR). The animals were pretreated with

DEC (50 mg/kg, v.o), CUR (50 mg/kg, i.p)

or distilled water for three consecutive days

before pleurisy. One way analysis of

variance (ANOVA) was performed by

Tukey post-hoc test, and values were

considered statistically significant when p <

0.05. DEC pretreatment reduced tissue

damage (Figure 2) and the production of

inflammatory markers, such as NO, iNOS,

PGE2, COX-2, and PARP induced by

carrageenan. Similarly, a known inhibitor

of NF-κB pathway (curcumin) was also

able to reduce these parameters. Like

curcumin, DEC prevents NF-κB activation

by reducing NF-κB p65 phosphorylation

and IκBα degradation. DEC prevented NF-

κB activation via p38 MAPK, but did not

interfere in the ERK pathway in this

experimental model. However, further

studies should be developed to confirm this

hypothesis. These findings suggest that

DEC could be a promising drug for

inflammatory disorders, especially in

pulmonary diseases such as Acute Lung

Inflammation, due its high anti-

inflammatory potential which prevents NF-

κB activation (Santos et. al., International

Immunopharmacology, 2014).

Fig. 2. Effects of DEC on histological alterations

and cell migration. Representative analysis of the

CAR group (b) revealed areas of alveolar

thickening (white arrow), edema (asterisk) and

PMN infiltration (black arrow). The DEC

pretreatment reduced these abnormalities (c).

Similarly, CUR induced similar effects (d). No

pathologic changes were found in the control

group (SAL) (a). Intense cell migration was

observed in the CAR group (e), mainly

neutrophils, which were confirmed by MPO

assays (f). Blood vessel (v), alveolar space (a), scale

bars 50 μm, H&E stained. The data were

representative of at least three independent

experiments. The results are expressed as the

means ± s.e.m. of ten mice in each group. # P b

0.001 CAR vs. control (SAL); ** P b 0.0001 DEC

vs. CAR group; ** P b 0.0001 CUR vs. CAR

group.

Induction of NF-κB-mediated gene

expression has been identified in the

pathogenesis of alcoholic liver disease

(ALD). The present study was designed to

evaluate the effect of DEC on NF-κB

pathways in mice undergoing alcoholism

induced hepatic inflammation. Forty male

C57BL/6 mice were divided equally into

four groups: control group (C); DEC-


135

treated group, which received 50 mg/kg

(DEC50); alcoholic group (EtOH),

submitted to chronic alcohol consumption

and the alcohol-DEC treated group

(EtOH50), submitted to chronic alcoholism

consumption plus DEC treatment.

Histological analysis of the alcoholic group

showed evident hepatocellular damage

which was reduced in EtOH50 group

(Figure 3). Immunohistochemistry and

western blot results showed elevated

expression of inflammatory markers such as

MDA, TNF-α, IL-1β, COX-2 and iNOS in

hepatocytes of EtOH group. However, low

immunopositivity for these markers was

detected following DEC treatment. In the

EtOH group the activation of NF-κB was

observed by an increase in the expression of

both NF-κB and pNF-κB in hepatocytes.

This expression was significantly reduced

in livers of EtOH50 group. Protein

expression of Iκβα was measured to

determine whether activation of NF-κB

might be the result of Iκβα degradation. It

was observed that expression of this protein

was low in EtOH group, while animals

treated with DEC had a high expression of

Iκβα. The results of the present study

indicate that DEC alleviates alcoholic liver

injury, in part by the inhibiting activation of

NF-κB and by suppressing the induction of

NF-κB-dependent genes (Silva et. al.,

Tissue and Cell, 2014).

Fig. 3. Micrograph of hepatocytes. (A) Liver parenchyma from control group showing typical morphology, (B)

Group treated with 50 mg/kg DEC (DEC50), (C) Alcoholic group (EtOH), (D) Alcoholic plus DEC group

(EtOH50). Hepatic venule (V), lipid droplets (arrow), inflammatory infiltrates (star), necrosis (arrowheads),

cords of hepatocytes (asterisk). HE staining. Bars = 20 μm

anti-inflammatory action of a novel

synthetic thiazolidine derivative

LPSF/RA-4

A number of studies have demonstrated the

biological activities of peroxisome

proliferator-activated receptors. However,

few studies have addressed the effects of

the agonists of these receptors on lung

diseases. The aim of the present study was

to evaluate the anti-inflammatory action of

a novel synthetic thiazolidine derivative

(5Z)-3-benzyl-5-(1H-indol-3-ylmethylene)-

thiazolidine-2,4-dione (LPSF/RA-4) on

acute lung inflammation (pleurisy) induced

by carrageenan. Forty mice were randomly

allocated to the following groups: (I) saline

control group (sham); (II) carrageenan

(CAR) group; (III) CAR+LPSF/RA-4


136

group treated with LPSF/RA-4 (60

μmol/kg); and (IV) INDO group treated

with indometacin (5 mg/kg). Total cell

counts and the measure of nitric oxide (NO)

were performed in pleural exudates. Lung

fragments were processed for light

microscopy, transmission electron

microscopy, immunohistochemistry and

Western blotting. The influx of leucocytes

and NO levels were significantly reduced

following treatment with LPSF/RA-4 and

INDO. Histopathological and ultrastructural

analyses of the CAR group revealed evident

tissue alterations, such as oedema,

infiltrates of inflammatory cells and

emphysema (Figure4). These alterations

were significantly reduced in the groups

treated with LPSF/RA-4 or INDO.

Immunohistochemistry revealed an increase

in inflammatory markers (COX-2, iNOS,

TNF-α and IL-1β) in the lung tissue of the

CAR group, whereas the groups treated

with LPSF/RA-4 and INDO exhibited

significant reductions in such

immunomarkers. Western blot analysis

revealed an increased expression of COX-2

and IL-1 in the CAR group, which was

reduced by treatment with LPSF/RA-4. The

present findings demonstrate the potent

anti-inflammatory action of the novel

derivative thiazolidinedione LPSF/RA-4 in

acute lung injury induced by carrageenan

(Barbosa et. al., Eur. J. of Pharmacology,

20013).

Figure 4: Ultrastructural analysis of lung after carrageenan-induced injury and LPSF/RA-4 treatment. (A)

Lung sections from mice in sham group (note preserved lung architecture). (B) Lung with carrageenan-

induced pleurisy showing inflammatory cells (asterisk) and activated alveolar epithelial cells (arrows) (note

cellular debris). (C) Lung treated with LPSF/RA-4 exhibiting well-preserved pneumocytes and alveoli. (D)

Ultrathin sections of lungs from INDO group demonstrating reduction in lung injury. Bar = 5 μm.

Folicular development

The effects of varying concentrations of

EGF were evaluated in terms of in vitro

follicular development and the mRNA

expression levels of EGF, EGF-R, FSH-R

and P450 aromatase. After 6 days, the

addition of 50 ng/mL of EGF to the culture

medium increased the antrum formation

rates in comparison to cultured control and

after 18 days of culture produced oocytes

with higher rates of meiosis resumption

when compared to the other treatments

(P<0.05) (Figure 5). The daily follicular

growth rates in presence of EGF (50 or

100) were increased in comparison to the

cultured control (P<0.05) (Figure 6).

Treatment with EGF 50 stimulated the

expression of EGF mRNA but reduced

EGF-R mRNA expression and estradiol

secretion as compared to the cultured

control (P<0.05). After 18 days of culture,

the mRNA levels for FSH-R and P450


137

aromatase were greater than those of the

non-cultured controls (P<0.05). In

conclusion, the effects of EGF treatment on

the mRNA levels for EGF, EGF-R, FSH-R,

and P450 aromatase varied according to the

stage of follicle development (Silva et. al.,

Res Vet Sci, 2013).

Fig. 5. Goat oocytes generated following the in vitro growth and maturation of secondary follicles. (A) Non-

stained oocyte (diameter P110 lm), (B) viable oocyte labeled with calcein-AM (green), (C) non-viable oocyte

labeled with ethidium homodimer-1 (red), (D) oocyte showing an intact nuclear membrane, germinal vesicle

(GV), (E) oocyte showing germinal vesicle breakdown (GVBD), and (F) oocyte in metaphase I (MI). (For

interpretation of the references to color in this figure legend, the reader is referred to the web version of this

article.)

Fig. 6. Ultrastructural analysis of goat secondary follicle after 18 days of in vitro culture. (A and B) a-MEM+

alone (cultured control). (C and D) a-MEM+ plus EGF at 50 ng/mL (EGF 50). ZP indicates the zona pellucida;

M, mitochondria; R, reticulum; Nu, nucleus.


138


1. AIRES, ANDRÉ DE LIMA ; XIMENES, EULÁLIA CAMELO PESSOA AZEVEDO ; SILVA, RENATA

ALEXANDRE RAMOS ; BARBOSA, VANESSA XAVIER ; GÓES, ALEXANDRE JOSÉ DA SILVA ; Peixoto, Christina Alves ; SOUZA, VALDÊNIA MARIA OLIVEIRA ; ALBUQUERQUE, MÔNICA CAMELO PESSÔA DE

AZEVEDO . Ultrastructural analysis of β-lapachone-induced surface membrane damage in male adult Schistosoma

mansoni BH strain worms. Experimental Parasitology, v. 142, p. 83-90, 2014. http://dx.doi.org/10.1016/j.exppara.2014.04.010

2. ALVES PEIXOTO, CHRISTINA; DA SILVA, BRUNA SANTOS . Anti-inflammatory effects of diethylcarbamazine: A

review. European Journal of Pharmacology, v. 734, p. 35-41, 2014. http://dx.doi.org/10.1016/j.ejphar.2014.03.046 3. ANDR, L. S. BARROS ; JACIANA, S. AGUIAR ; LARISSA, C. C. ARAJO ; CHRISTINA, A. PEIXOTO ; PALOMA,

L. DE MEDEIROS ; MARIA, TERESA J. A. CATANHO ; TERESINHA, GONALVES DA SILVA . Synergistic

anticancer effects of valproic acid, atorvastatin and pioglitazone in human malignant and murine cells. African Journal of Pharmacy and Pharmacology, v. 8, p. 31-39, 2014. http://dx.doi.org/10.5897/AJPP2013.3797

4. DOS SANTOS, LAISE ALINE MARTINS ; RIBEIRO, EDLENE LIMA ; BARBOSA, KARLA PATRÍCIA SOUSA ;

FRAGOSO, INGRID TAVARES ; GOMES, FABIANA OLIVEIRA DOS SANTOS ; DONATO, MARIANA ARAGÃO MATOS ; DA SILVA, BRUNA SANTOS ; SILVA, AMANDA KAROLINA SOARES ; ROCHA, SURA

WANESSA SANTOS ; DE FRANÇA, MARIA EDUARDA ROCHA ; RODRIGUES, GABRIEL BARROS ; SILVA,

TERESINHA GONÇALVES ; Peixoto, Christina Alves . Diethylcarbamazine inhibits nuclear factor-κb activation in

acute lung injury induced by carrageenan in mice. International Immunopharmacology (Print), v. 23, p. 153-162, 2014.

http://dx.doi.org/10.1016/j.intimp.2014.08.017

5. GOMES, FABIANA OLIVEIRA DOS SANTOS ; CARVALHO, MARIA DA CONCEIÇÃO ; Saraiva, Karina Lidianne Alcântara ; RIBEIRO, EDLENE LIMA ; E SILVA, AMANDA KAROLINA SOARES ; DONATO, MARIANA

ARAGÃO MATOS ; ROCHA, SURA WANESSA SANTOS ; E SILVA, BRUNA SANTOS ; Peixoto, Christina Alves .

Effect of chronic Sildenafil treatment on the prostate of C57Bl/6 mice. Tissue & Cell, v. 46, p. 439-449, 2014. http://dx.doi.org/10.1016/j.tice.2014.08.001

6. LEMOS, ANA JANAINA JEANINE M. ; Peixoto, Christina A. ; TEIXEIRA, ÁLVARO AGUIAR C. ; LUNA,

RAYANA LEAL A. ; ROCHA, SURA WANESSA S. ; SANTOS, HILDA MICHELLY P. ; SILVA, AMANDA KAROLINA S. ; NUNES, ANA KAROLINA S. ; WANDERLEY-TEIXEIRA, VALÉRIA . Effect of the combination of

metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and

histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome. Toxicology and Applied Pharmacology, v. 280, p. 159-168, 2014. http://dx.doi.org/10.1016/j.taap.2014.05.015

7. RAPÔSO, CATARINA ; LUNA, RAYANA LEAL DE ALMEIDA ; NUNES, ANA KAROLINA SANTANA ; THOMÉ, RODOLFO ; Peixoto, Christina Alves . Role of iNOS-NO-cGMP signaling in modulation of inflammatory and

myelination processes. Brain Research Bulletin, v. 104, p. 60-73, 2014.

http://dx.doi.org/10.1016/j.brainresbull.2014.04.002 8. RIBEIRO, EDLENE LIMA ; BARBOSA, KARLA PATRICIA DE SOUZA ; FRAGOSO, INGRID TAVARES ;

DONATO, MARIANA ARAGÃO MATOS ; OLIVEIRA DOS SANTOS GOMES, FABIANA ; SILVA, BRUNA

SANTOS DA ; SILVA, AMANDA KAROLINA SOARES E ; ROCHA, SURA WANESSA SANTOS ; AMARO DA SILVA JUNIOR, VALDEMIRO ; Peixoto, Christina Alves . Diethylcarbamazine Attenuates the Development of

Carrageenan-Induced Lung Injury in Mice. Mediators of Inflammation, v. 2014, p. 1-12, 2014.

http://dx.doi.org/10.1155/2014/105120 9. RIBEIRO, REGISLANE P. ; PORTELA, ANTONIA M.L.R. ; SILVA, ANDERSON W.B. ; COSTA, JOSÉ J.N. ;

PASSOS, JOSÉ R.S. ; CUNHA, ELLEN V. ; SOUZA, GLAUCINETE B. ; SARAIVA, MÁRCIA V.A. ; DONATO,

MARIANA A. M. ; PEIXOTO, CHRISTINA. A. ; VAN DEN HURK, ROBERT ; SILVA, JOSÉ R.V. . Effects of jacalin and follicle-stimulating hormone on in vitro goat primordial follicle activation, survival and gene expression.

Zygote (Cambridge. Print), v. 29, p. 1-13, 2014. http://dx.doi.org/10.1017/s0967199414000173

10. ROCHA S.W.A. ; PEIXOTO, C.A. . Arachidonic Acid, Cyclooxygenase and Hepatic Inflammation. In: Jason M. O'Keefe. (Org.). Arachidonic Acid: Sources, Biosynthesis and Health Effects. 1ed.New York: , 2014, v. , p. 127-134.

[BOOK CHAPTER]

11. ROCHA, SURA WANESSA SANTOS ; FRANÇA, MARIA EDUARDA ROCHA DE ; RODRIGUES, GABRIEL BARROS ; BARBOSA, KARLA PATRÍCIA SOUSA ; NUNES, ANA KAROLINA SANTANA ; PASTOR, ANDRÉ

FILIPE ; OLIVEIRA, ANNE GABRIELLE VASCONCELOS ; OLIVEIRA, WILMA HELENA ; LUNA, RAYANA

LEAL ALMEIDA ; Peixoto, Christina Alves . Diethylcarbamazine Reduces Chronic Inflammation and Fibrosis in Carbon Tetrachloride- (CCl 4 -) Induced Liver Injury in Mice. Mediators of Inflammation (Print), v. 2014, p. 1-15, 2014.

http://dx.doi.org/10.1155/2014/696383

12. SILVA, ANEKÉCIA ; OLIVEIRA, SHEILLA ; OLIVEIRA, JAMERSON ; SANTIAGO, EDNA ; JÚNIOR, ANTÔNIO ; JACOBI, ÍRIS ; PEIXOTO, CHRISTINA ; ROCHA, VINÍCIUS ; SOARES, MILENA ; PITTA, IVAN ; LIMA,

MARIA . Tegumental Changes in Adult Schistosoma mansoni Induced by a New Imidazolidinic Derivative. British

Journal of Pharmaceutical Research, v. 4, p. 1988-2005, 2014. http://dx.doi.org/10.9734/bjpr/2014/12511 13. SILVA, BRUNA SANTOS DA ; RODRIGUES, GABRIEL BARROS ; ROCHA, SURA WANESSA SANTOS ;

RIBEIRO, EDLENE LIMA ; GOMES, FABIANA OLIVEIRA DOS SANTOS ; SILVA, AMANDA KAROLINA

SOARES E ; Peixoto, Christina Alves . Inhibition of NF-κB activation by Diethylcarbamazine prevents alcohol-induced liver injury in C57BL/6 mice. Tissue & Cell, v. 14, p. S0040-s0047, 2014. http://dx.doi.org/10.1016/j.tice.2014.06.008

14. SOARES, A. T. ; SILVA, S. V. ; BATISTA, A. M. ; ALMEIDA, F. C. ; NUNES, J. F. ; PEIXOTO, C. A. ; GUERRA,

M. M. P. . Ultrastructure evaluation of goat spermatozoa after freezing in a skim milk-based extender with Trolox supplementation. Andrologia (Berlin), v. 2, p. n/a-n/a, 2014. http://dx.doi.org/10.1111/and.12279


1. ALBUQUERQUE COUTO, JANAÍNA ; SARAIVA, KARINA LIDIANNE ALCÂNTARA ; BARROS, CLEITON

DINIZ ; UDRISAR, DANIEL PEDRO ; PEIXOTO, CHRISTINA ALVES ; VIEIRA, JULIANY SILVEIRA BRAGLIA CÉSAR ; CARMO ALVES DE LIMA, MARIA ; GALDINO, SUELY LINS ; ROCHA PITTA, IVAN ; WANDERLEY,

MARIA INÊS . Effect of chronic treatment with new benzylidene-thiazolidine-2,4-dione (LPSF/GQ-06) with potential

hypoglycemic on rat Leydig cell steroidogenesis. Medicinal Chemistry Research (Print), v. 22, p. 617-716, 2013. http://dx.doi.org/10.1007/s00044-012-0024-z


139

2. BARBOSA, KARLA P.S. ; SANTOS, LAISE A.M. ; RIBEIRO, EDLENE L. ; FRAGOSO, INGRID T. ; ROCHA,

SURA W.S. ; NUNES, ANA K.S. ; FRANÇA, MARIA E.R. ; SILVA, BRUNA S. ; SILVA, AMANDA K.S.E. ;

DONATO, MARIANA A.M. ; GOMES, FABIANA O.S. ; SILVA, TERESINHA G. ; PITTA, IVAN R. ; PITTA,

MARINA R. ; LIMA, MARIA C.A. ; UCHÔA, FLÁVIA D.T. ; GALDINO, SUELY L. ; Peixoto, Christina A. .

Reduction of carrageenan-induced acute pulmonary inflammation in mice by novel thiazolidinedione derivative LPSF/RA-4. European Journal of Pharmacology, v. 11, p. 1, 2013. http://dx.doi.org/10.1016/j.ejphar.2013.08.033

3. CAMPOS, INGRID ARAÚJO ; XIMENES, EULÁLIA AZEVEDO ; CARVALHO JÚNIOR, CARLSON HELDER R. ;

DE MESQUITA, AMANDA RAFAELA C. ; SILVA, JOSÉ BRUNO N.F. ; MAIA, MARIA BERNADETE S. ; FRANCO, ERYVELTON SOUZA ; MEDEIROS, PALOMA LYS ; Peixoto, Christina A. ; DA SILVA, TERESINHA

GONÇALVES . Zymomonas mobilis culture protects against sepsis by modulating the inflammatory response,

alleviating bacterial burden and suppressing splenocyte apoptosis. European Journal of Pharmaceutical Sciences, v. 48, p. 1-8, 2013. http://dx.doi.org/10.1016/j.ejps.2012.10.011

4. CUNHA, E. V. ; CUNHA, J. J. ; ROSSI, R. O. ; SILVA, A. W. ; PASSOS, J. R. ; PORTELA, A. M. ; PEREIRA, D. C. ; Donato, M. A. M. ; Campello, C.C. ; Silva J.R.V. ; Peixoto, Cristina ; Saraiva M.V. ; SANTOS, R. P. .

Phytohemagglutinin improves the development and ultrastructure of in vitro-cultured goat (Capra hircus) preantral

follicles.. Brazilian Journal of Medical and Biological Research on line, v. 19, p. 245-252, 2013. 5. Donato, M. A. M. ; Ribeiro E.L. ; SILVA, Y. J. A. ; PEIXOTO, C.A. . Além da disfunção erétil. Cadernos de Graduação

Ciências Biológicas e da Saúde - FACIPE, v. 1, p. 11-21, 2013.

6. MOURA, C.S. ; NUNES, A.K.S. ; SILVA, B.S. ; PEIXOTO, C.A. ; SILVA, A.R. ; SILVA, S.V. ; GUERRA, M.M.P. . Efeito da temperatura de descongelação na integridade de espermatozoides criopreservados de cães. Arquivo Brasileiro

de Medicina Veterinária e Zootecnia, v. 65, p. 1057-1064, 2013. http://dx.doi.org/10.1590/S0102-09352013000400017

7. PASSOS, M.J. ; VASCONCELOS, G.L. ; SILVA, A.W.B. ; BRITO, I.R. ; SARAIVA, M.V.A. ; MAGALHÃES, D.M. ; COSTA, J.J.N. ; Donato, M.A.M. ; RIBEIRO, R.P. ; CUNHA, E.V. ; PEIXOTO, C.A. ; Campello, C.C. ; Figueiredo,

J.R. ; VAN DEN HURK, R. ; SILVA, J.R.V. . Accelerated growth of bovine preantral follicles in vitro after stimulation

with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia. Theriogenology, v. 79, p. 1269-1277, 2013. http://dx.doi.org/10.1016/j.theriogenology.2013.02.023

8. RAPOSO, CATARINA ; NUNES, ANA KAROLINA DE SANTANA ; LUNA, RAYANA LEAL DE ALMEIDA ;

ARAÚJO, SHYRLENE MEIRY DA ROCHA ; DA CRUZ-HÖFLING, MARIA ALICE ; Peixoto, Christina Alves . Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory

Demyelination Model. Mediators of Inflammation (Print), v. 2013, p. 1-11, 2013. http://dx.doi.org/10.1155/2013/321460

9. SILVA, A.W.B. ; BEZERRA, F.T.G. ; COSTA, J.J.N. ; ROSSI, R.O.D.S. ; PASSOS, M.J. ; VASCONCELOS, G.L. ; ROSSETTO, R. ; Donato, M.A.M. ; MAGALHÃES-PADILHA, D.M. ; Campello, C.C. ; SARAIVA, M.V.A. ;

Figueiredo, J.R. ; PEIXOTO, C.A. ; VAN DEN HURK, R. ; SILVA, J.R.V. . Differential effects of activin-A and FSH

on growth, viability and messenger RNA expression in cultured bovine preantral follicles. Livestock Science (Print), v. 160, p. 199-207, 2013. http://dx.doi.org/10.1016/j.livsci.2013.12.003

10. SILVA, C.M.G. ; CASTRO, S.V. ; FAUSTINO, L.R. ; Rodrigues, G.Q. ; BRITO, I.R. ; ROSSETTO, R. ; SARAIVA,

M.V.A. ; Campello, C.C. ; LOBO, C.H. ; SOUZA, C.E.A. ; MOURA, A.A.A. ; Donato, M.A.M. ; PEIXOTO, C.A. ; Figueiredo, J.R. . The effects of epidermal growth factor (EGF) on the in vitro development of isolated goat secondary

follicles and the relative mRNA expression of EGF, EGF-R, FSH-R and P450 aromatase in cultured follicles. Research

in Veterinary Science, v. 94, p. 453-461, 2013. doi: 10.1016/j.rvsc.2012.12.002 11. SILVA, SILDIVANE VALCÁCIA ; SOARES, ADRIANA TRINDADE ; BATISTA, ANDRÉ MARIANO ;

ALMEIDA, FELIPE COSTA ; NUNES, JOSÉ FERREIRA ; Peixoto, Christina Alves ; GUERRA, MARIA

MADALENA PESSOA . Vitamin E (Trolox) addition to Tris-egg yolk extender preserves ram spermatozoon structure and kinematics after cryopreservation. Animal Reproduction Science (Print), v. 137, p. 37-44, 2013.

http://dx.doi.org/10.1016/j.anireprosci.2012.12.002

12. SOARES E SILVA, AMANDA KAROLINA ; DE OLIVEIRA CIPRIANO TORRES, DILÊNIA ; SANTOS ROCHA, SURA WANESSA ; DOS SANTOS GOMES, FABIANA OLIVEIRA ; DOS SANTOS SILVA, BRUNA ; DONATO,

MARIANA ARAGÃO MATOS ; RAPOSO, CATARINA ; SANTOS, ANA CÉLIA OLIVEIRA ; De Lima, Maria do

Carmo Alves ; LIMA, M. C. A. ; Galdino, Suely Lins ; da Rocha Pitta, Ivan ; DE SOUZA, JOSÉ ROBERTO BOTELHO ; PEIXOTO, C. A. . Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic

lesions in LDL receptor-deficient mice (LDLR−/−). Cardiovascular Pathology, v. 22, p. 81-90, 2013.

http://dx.doi.org/10.1016/j.carpath.2012.05.006 13. TENORIO, BRUNO MENDES ; FERREIRA FILHO, MOISÉS BONIFACIO ALVES ; JIMENEZ, GEORGE CHAVES

; MORAIS, ROSANA NOGUEIRA DE ; PEIXOTO, C. A. ; NOGUEIRA, ROMILDO DE ALBUQUERQUE ; SILVA

JUNIOR, V. A. ; SILVA JUNIOR, VALDEMIRO AMARO DA . Extremely low-frequency magnetic fields can impair spermatogenesis recovery after reversible testicular damage induced by heat. Electromagnetic Biology and Medicine, v.

na, p. 1-8, 2013. http://dx.doi.org/10.3109/15368378.2013.795156

14. WANDERLEY, MARIA I. ; SARAIVA, KARINA L. A. ; CÉSAR VIEIRA, JULIANY S. B. ; PEIXOTO, CHRISTINA A. ; UDRISAR, DANIEL P. . Foetal exposure to Panax ginseng extract reverts the effects of prenatal dexamethasone in the synthesis of testosterone by Leydig cells of the adult rat. International Journal of Experimental Pathology (Print), v.

94, p. 230-240, 2013. http://dx.doi.org/10.1111/iep.12026


140

AL 16 - Associate Laboratory of Molecular And Cellular

Cardiology

- Coordinator:

Antonio Campos de Carvalho – IBCCF/UFRJ.


Adriana Bastos Carvalho - IBCCF/UFRJ

Emiliano Horacio Medei - Xerém/UFRJ

Regina Coeli dos Santos Goldenberg - IBCCF/UFRJ

- Researchers from international institutions:

Antonio Carlos Campos de Carvalho - Albert Einstein College of Medicine - NY/USA


Bruno da Rocha Azevedo (IBCCF/UFRJ),

Camila Hochman Mendez (IBCCF/UFRJ),

Camila Iansen Irion (IBCCF/UFRJ),

Danubia Silva dos Santos (IBCCF/UFRJ),

Debora Bastos Mello (IBCCF/UFRJ),

Fernanda Cristina Paccola Mesquita

(IBCCF/UFRJ),

Gustavo Monnerat Cahli (IBCCF/UFRJ),

Karina Dutra Asensi (IBCCF/UFRJ),

Tais Hanae K. Brunswick (IBCCF/ UFRJ),

Vivian Miranda Lago (IBCCF/UFRJ).


Ainhoa Rodriguez Y. Guirao (IBCCF/UFRJ),

Alan Cesar Nunes de Moraes

(HUCFF/UFRJ),

Andreza Bastos Martins (IBCCF/UFRJ),

Bernardo Jorge da S. Mendes (IBCCF/UFRJ),

Bruna Farjun (IBCCF/UFRJ),

Danubia Silva dos Santos (IBCCF/UFRJ),

Dayana da Silva de Araújo (IBCCF/UFRJ),

Isalira Peroba Rezende Ramos

(HUCFF/UFRJ),

Janaína José S. Machado (HUCFF /UFRJ),

Lanuza Alaby P. Faccioli (HUCFF /UFRJ),

Marcus Vinicius Naghetini dos Santos

(IBCCF/UFRJ),

Maria Julieta F. Ruocco (IBCCF /UFRJ),

Maria Micaela L. Alarcon (IBCCF /UFRJ),

Rafael Serafim Pinto (IBCCF/UFRJ),

Raiana Andrade Q. Barbosa (IBCCF/UFRJ),

Suzana Kelly Abreu (IBCCF/UFRJ).


Ataide Mendonça (IBCCF/UFRJ),

Beatriz Toja de Miranda (IBCCF/UFRJ),

Eduardo B. de Carvalho (IBCCF/UFRJ),

Elias Sandro T. da Silva (IBCCF/UFRJ), Madellon Melo de Assis (IBCCF/UFRJ),

Michelle Lopes Araujo (IBCCF/UFRJ),

Rosana de Almeida Santos (IBCCF/UFRJ).


Bruno Simas de Queiroz (UFRJ),

Cibele Ferreira Pimentel (UFRJ),

Gabriela Corrêa Gorga (UFRJ),

Hugo Justino Branda (IBCCF/UFRJ),

Isabela de Carvalho Leitão (UFRJ),

Isabelle Alves Ramos (UFRJ),

Joyce Cristina Guimarães de Oliveira (UFRJ),

Júlia do Carmo Silveira (UFRJ),

Julia Helena Oliveira de Barros (UFRJ),

Larissa Milani (UFRJ), Luana Ker

(IBCCF/UFRJ),

Lucas dos Santos Silva (UFRJ),

Mariana Fernandes de Lima (UFRJ),

Teby Melo da Silva (UFRJ),

Úrsula Maria Coelho Bastos (UFRJ),

Victor Hoff (UFRJ),

Vitoria Santorio (IBCCF/UFRJ),

Ygor Schleier (IBCCF/UFRJ).

- Technicians:

Ana Célia Sá de Carvalho (IBCCF/UFRJ),

Cíntia Marina Paz Batista (IBCCF/UFRJ),

Cleusa Schafhauser (IBCCF/UFRJ),

Dilza Balteiro Pereira de Campos

(IBCCF/UFRJ).


141

The Laboratory of Molecular and Cellular

Cardiology developed research lines

encompassing basic, pre-clinical and clinical

research focused on stem cells and cell

therapies.

In basic research, we pursued reprogramming

skin fibroblasts and erythroblasts from

peripheral blood samples into induced

pluripotent stem cells (iPS). The technique is

now established in the laboratory and we have

opted to use the Sendai virus transduction

system, due to its non integrating characteristic

(see Figure 1)

Figure 1: Expressions of pluripotency markers by immunofluorescence: OCT4, SOX2, NANOG, cMYC and LIN28

are shown in red, SSEA4 and TRA-1–60 are shown in green and nuclei are stained in blue.

.

In collaboration with the National Cardiology

Institute we have derived a number of iPS

from patients with Long QT Syndrome

(LQTS) and are now differentiating these iPS

into cardiomyocytes to study their cell

biological and electrophysiological properties.

Some of the patients selected display

mutations that have not yet been described in

the literature and the iPS generated from these

patients will also be corrected by CRISPR-

Cas9 to generate control cardiomyocytes with

the same genetic background.

The establishment of a robust method to

differentiate pluripotent cells into

cardiomyocytes has been another achievement

of the Laboratory. We have been able to

consistently differentiate these cells into

cardiac myocytes and record action potentials

from them using both microelectrodes and

patch techniques.

Currently we are establishing multi-electrode

array (MEA) recordings from these cells,

measuring action potential propagation under

spontaneous and paced conditions. This will

allow us to measure QT intervals (through

filed potentials), and record propagation and

conduction disturbances in embryoid bodies or

monolayers of cardiomyocytes derived from

patient's iPS.

Another line we have been developing in basic

research is the decellularization and

recellularization of heart and liver. We have

succeeded in decellularizing both organs in

rats and pigs and are now characterizing the

composition of the extracellular matrix and its

biophysical properties (in both intact and


142

decellularized states). We are also

investigating the capacity of the matrix to

induce the differentiation of pluripotent cells

into the cell types of the constituting matrix.

In the pre-clinic field, we have tested a number

of different adult and embryonic stem cells in

models of acute and chronic myocardial

infarction, in acute and chronic chagasic

cardiomyopathy and in diabetic

cardiomyopathy. We tested bone marrow and

adipose derived mesenchymal stem cells

(MSC) in murine models of both diseases.

We also developed tools to track these cells by

bioluminescence and fluorescence in whole

animals (see Figure 2).

Figure 2. Tracking of X-Sight-labeled MSCs in control and chagasic mice 2 or 15 days after cell transplantation. The

cells were intravenously injected (tail vein) in control and chagasic animals 1 month after infection for tracking by

IVIS. (A) Representative images showing the distribution of transplanted MSCs viewed from in the ventral surface of

the body. (B) Images of ex vivo organs showing the distribution of labeled MSCs. Note the majority of the signal is

localized in the lung, liver and spleen of the animals. The evaluated organs were (C) heart, (D) bladder, (E) lung, (F)

liver, (G) spleen and (H) kidney. P<0.05

Furthermore, we established echo-guided

intramyocardial injection of stem cells into

mice and rat hearts, thus avoiding the need for

open-chest surgery for the intramyocardial cell

injection. For evaluation of cardiac function

we established protocols for measurement of

ejection fraction by MRI and are now

comparing these results to those obtained by

high resolution echocardiography (using the

VisualSonics Vevo 2100).

We have also explored coupling gene to cell

therapy in myocardial ischemia. Most of the

cell therapy pre-clinical trials using MSC have

been published and are listed in the

Publications of the Laboratory. In addition to

these MSC trials, we tested two additional cell

types in murine models of myocardial

infarction and chronic chagasic

cardiomyopathy - cardiosphere derived cells

(CDC) and cardiomyocytes derived from

embryonic stem cells (ESC), respectively. The

article related to the use of CDC in myocardial

infarction is now submitted to publication and

the one related to the use of ESC derived

cardiomyocytes is being written.


143

Due to the failure of translating the pre-clinical

trials in rodents to humans (see below) we

have invested in medium sized animal models.

In collaboration with the Federal University of

Ouro Preto we are testing MSC cell therapies

in a chronic model of canine Chagas

cardiomyopathy. In this model we have

established that autologous MSC are better

than allogeneic MSC, as measured by

echocardiographic ejection fraction (EF%)

determination.

We are now treating the chagasic dogs with

pharmacologic drugs currently used in heart

failure therapy and will test if the autologous

MSC are capable of improving cardiac

function in drug treated animals. In myocardial

infarction we established a collaboration with

Sírio-Libanes Hospital to test MSC in a pig

model. These experiments are currently

underway.

Finally, in the clinical arena we have

conducted clinical trials using bone marrow

derived mononuclear cells in randomized,

double-blinded and placebo controlled trials.

Although these clinical trials were not an

integral part of this INCT project, all the work

developed in the pre-clinical models had a

clear translational purpose. We have

completed evaluation of the efficacy of the cell

therapy in three cardiac diseases:

- Chagasic cardiomyopathy (published in

Circulation in 2012);

- Dilated cardiomyopathy (published in

European Heart Journal, 2015);

- Acute myocardial infarction (not yet

published).

Unfortunately, in all three diseases, therapy

using the mononuclear cells from bone

marrow did not improve cardiac function, as

measured by EF%. These negative results have

led us to test new cell types and to establish

medium size animal models as described

above, attempting to gather scientific evidence

that would justify proposing a new clinical

trial to the health authorities in Brazil.


1. DE ARAÚJO, C. C. ; Marques, P. S ; SILVA, J. D. ; SAMARY, C. S. ; DA SILVA, A. L. ; HENRIQUES, I. ; ANTUNES, M. A. ; DE OLIVEIRA,

M. V. ; GOLDENBERG, R. C. ; MORALES, M. M. ; ABREU, I. ; DIAZ, B. L. ; ROCHA, N. N. ; CAPELOZZI, V. L. ; ROCCO, P. R. M. .

Regular and moderate aerobic training before allergic asthma induction reduces lung inflammation and remodeling. Scandinavian Journal of

Medicine & Science in Sports , v. x, p. n/a-n/a, 2016. http://dx.doi.org/10.1111/sms.12614

2. GADELHA, CARLOS AUGUSTO GRABOIS ; COSTA, KAREN SARMENTO ; NASCIMENTO JÚNIOR, JOSÉ MIGUEL DO ; SOEIRO,

ORLANDO MÁRIO ; MENGUE, SOTERO SERRATE ; MOTTA, MÁRCIA LUZ DA ; CARVALHO, ANTÔNIO CARLOS CAMPOS DE .

PNAUM: integrated approach to Pharmaceutical Services, Science, Technology and Innovation. Revista de Saúde Pública (Online) , v. 50, p. 1s-8s,

2016. http://dx.doi.org/10.1590/s1518-8787.2016050006153

3. GOLDENBERG, R.C.S.; Mello, D.B. ; ASENSI, K. D. . Mesenchymal Stem/Stromal Cells from Adult Tissues. In: Mariana Garcia; Marcela

Bolontrade. (Org.). Mesenchymal Stromal Cells as Tumor Stromal Modulators. 1ed.: Academic Press, 2016, v. 1, p. 1-. (CHAPTER BOOK)

4. GUIMARÃES, IH ; PADILHA, G. A. ; HUHLE, R. ; WIERZCHON, C. ; MIRANDA, P. ; RAMOS, I. ; ROCHA, N. ; CRUZ FF ; SANTOS, R. S.

; OLIVEIRA, M. V. ; SOUZA, S. ; GOLDENBERG, R. C. S. ; LUIZ, R. R. ; PELOSI P ; ABREU MG ; SILVA, P. L. ; ROCCO, P. . Comparison

between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema. Frontiers in

Physiology , v. 7, p. 1, 2016. http://dx.doi.org/10.3389/fphys.2016.00277

5. JASMIN, . ; SOUZA GT ; LOUZADA RUY A.N ; CASTRO, P. H. R. ; MENDEZ-OTERO, R. ; CAMPOS DE CARVALHO, ANTONIO

CARLOS . Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations. International Journal of

Nanomedicine (Print) , 2016. *IN COLLABORATION WITH MENDEZ-OTERO (AL19).

6. MONNERAT, GUSTAVO ; ALARCÓN, MICAELA L. ; VASCONCELLOS, LUIZ R. ; HOCHMAN-MENDEZ, CAMILA ; BRASIL,

GUILHERME ; BASSANI, ROSANA A. ; CASIS, OSCAR ; MALAN, DANIELA ; TRAVASSOS, LEONARDO H. ; SEPÚLVEDA, MARISA ;

BURGOS, JUAN IGNACIO ; VILA-PETROFF, MARTIN ; DUTRA, FABIANO F. ; BOZZA, MARCELO T. ; PAIVA, CLAUDIA N. ;

CARVALHO, ADRIANA BASTOS ; BONOMO, ADRIANA ; FLEISCHMANN, BERND K. ; DE CARVALHO, ANTONIO CARLOS

CAMPOS ; MEDEI, EMILIANO . Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice. Nature Communications

, v. 7, p. 13344, 2016. http://dx.doi.org/10.1038/ncomms13344

7. PEREIRA, V. ; CARNEIRO VC ; MATA-SANTOS H ; VICENTINO RR ; RAMOS M ; GIAROLA NL ; FEIJÓ DF ; MEYER F ; MEDEI, E. ;

PAULA-NETO HA ; BOZZA MT ; JANES-VIEIRA J ; PAIVA, C. N. . Resveratrol Reverses Functional Chagas' Heart Disease in Mice. PLoS

Pathogens (Online), v. 9, p. 1-19, 2016. http://dx.doi.org/10.1371/journal.ppat.1005947

8. RAFAEL, J. F. ; CRUZ F E S ; CARVALHO, ANTONIO CARLOS C ; GOTTLIEB I ; CAZELLI J G ; SICILIANO A P ; DIAS G M . Myosin

Binding Protein C Double Heterozygous Variant Effect in the Phenotypic Expression of Hypertrophic Cardiomyopathy. Arquivos Brasileiros de

Cardiologia (Impresso) , 2016.

9. SCHERR, CARLOS ; DE CARVALHO, ANTONIO CARLOS ; BELEM, LUCIANO JUAÇABA ; LOYOLA, LUIZ HENRIQUE ; GUERRA,

RENATA LEBORATO ; BLANCO, FERNANDA ; MANGIA, CLAUDIO . Cardiovascular effects of SPARK conducted electrical weapon in

healthy subjects. International Journal of Cardiology (Print) , v. 225, p. 123-127, 2016. http://dx.doi.org/10.1016/j.ijcard.2016.08.321

10. SEPULVEDA, M. ; GONANO, L. A. ; VIOTTI, M. ; BLANCO, P. ; ALARCON, M. L. ; RAMOS, I. P. R. ; CARVALHO, A. B. ; MEDEI, E. H. ;

PETROFF, M. V. . Calcium/Calmodulin Protein Kinase II-Dependent Ryanodine Receptor Phosphorylation Mediates Cardiac Contractile

Dysfunction Associated With Sepsis. Critical Care Medicine, v. 1, p. 1, 2016. http://dx.doi.org/10.1097/CCM.0000000000002101


144


1. ALONSO, HIART ; JULIETA, F. ; GALLEGO, MONICA ; MALAGUETA-VIEIRA L ; RODRÍGUEZ-DE-YURRE A ; MEDEI, E. ; CASIS,

OSCAR . Thyroid stimulating hormone directly modulates cardiac electrical activity. Journal of Molecular and Cellular Cardiology , p. 123-234,

2015.

2. ANDRADE, BRUNO MOULIN ; BALDANZA, M. ; RIBEIRO, K. ; PORTO, A. ; PEÇANHA, RAMON ; FORTES, FABIO S.A. ; SUDO,

GISELE ZAPATA ; CAMPOS DE CARVALHO, A. C. ; GOLDENBERG, R.C.S. ; WERNECK-DE-CASTRO, JOÃO PEDRO S. . Bone Marrow

Mesenchymal Cells Improve Muscle Function in a Skeletal Muscle Re-Injury Model. Plos One, v. 10, p. e0127561, 2015

DOI:10.1371/journal.pone.0127561

3. AZEVEDO-PEREIRA, RL ; MORROT A ; MACHADO G S ; PAREDES, BRUNO DIAS ; RODRIGUES, D. C. ; CAMPOS DE CARVALHO,

ANTONIO C ; MENDEZ-OTERO, R. . Expression of ganglioside 9-O acetyl GD3 in undifferentiated embryonic stem cells. Cell Biology

International (Print) , v. 39, p. 121-127, 2015. http://dx.doi.org/10.1002/cbin.10335*IN COLLABORATION WITH MENDEZ-OTERO

(AL19).

4. CAMPOS DE CARVALHO, A. C. ; CARVALHO, A.B. . Stem Cell-Based Therapies in Chagasic Cardiomyopathy. BIOMED RES INT, v. 2015,

p. 1-5, 2015. DOI: 10.1155/2015/436314

5. DIAS F ; SORGINE M ; GUERRA, BÁRBARA ; MEDEI, E. ; REZENDE L ; PAIVA A ; VOLLU R ; OLIVEIRA S ; ALVES F ; OLIVEIRA PG

; SALMON D . Monitoring of the Parasite Load in the Digestive Tract of Rhodnius prolixus by Combined qPCR Analysis and Imaging Techniques

Provides New Insights into the Trypanosome Life Cycle. PLoS Neglected Tropical Diseases (Online) , v. 9, p. e0004186, 2015.

6. LINDOSO, RAFAEL S. ; SANDIM, VANESSA ; COLLINO, FEDERICA ; CARVALHO, ADRIANA B. ; DIAS, JULIANA ; DA COSTA,

MILENE R. ; ZINGALI, RUSSOLINA B. ; VIEYRA, ADALBERTO . Proteomics of cell-cell interactions in health and disease. Proteomics

(Weinheim. Print), v. 16, p. n/a-n/a, 2015. DOI:10.1002/pmic.201500341 *IN COLLABORATION WITH ZINGALI (AL4) AND VIEYRA

(AL17)

7. MELLO, DEBORA BASTOS ; RAMOS, I. P. ; MESQUITA, F. C. P. ; BRASIL, G. V. ; ROCHA, NAZARETH DE NOVAES ; TAKIYA,

CRISTINA MAEDA ; LIMA, A.P. ; CAMPOS DE CARVALHO, A. C. ; GOLDENBERG, R.C.S. ; CARVALHO, A. B. . Adipose Tissue-Derived

Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

PLoS Neglected Tropical Diseases (Online), v. 9, p. e0003945, 2015. DOI:10.1371/journal.pntd.0003945

8. MESQUITA, FERNANDA CRISTINA PACCOLA ; BRUNSWICK, TAIS HANAE KASAI ; GUBERT, FERNANDA DE MELLO SOUZA

VALENTE ; BORGONOVO, TAMARA ; SANTOS, DANÚBIA SILVA DOS ; DE ARAÚJO, DAYANA DA SILVA ; DE CARVALHO,

ANTONIO CARLOS CAMPOS ; Carvalho, Adriana Bastos . Generation of human iPS cell line ihFib3.2 from dermal fibroblasts. Stem Cell

Research (Amsterdam. Print), v. 15, p. 445-448, 2015. DOI:10.1016/j.scr.2015.09.001

9. MOARES, A. C. N. ; ANDRADE, C. B. V. ; NASCIMENTO, A. L. R. ; Salata, C ; RAMOS, I. P. ; GOLDENBERG, R.C. ; CARVALHO, J. J. ;

MACHADO, A. C. S. . A combination of stereological methods, biochemistry and electron microscopy for the investigation of drug treatment

effects in experimental animals. Journal of Microscopy (Print), p. n/a-n/a, 2015. DOI:10.1111/jmi.12329

10. MORALES, MARCELO MARCOS ; SOUZA, SAL ; LOIVOS, LP ; LIMA, MA ; SZKLO, A ; VAIRO, L. ; KASAI-BRUNSWICK, T. H. ;

GUTFILEN, BIANCA ; LOPES-PACHECO, M. ; ARAUJO, A ; CARDOSO, A ; GOLDENBERG, R.C.S. ; ROCCO, P. ; DA FONSECA, L. M.

B. ; LAPA E SILVA JR . Pilot safety study of intrabronchial instillation of bone marrow-derived mononuclear cells in patients with silicosis. BMC

Pulmonary Medicine (Online), v. 15, p. 1, 2015. DOI:10.1186/s12890-015-0061-8

11. NARAHASHI L ; CAMPOS DE CARVALHO ANTONIO C., ARAUJO, H. P. . Regulamentação das terapias celulares no Brasil. Vigilância

Sanitária em Debate: Sociedade, Ciência & Tecnologia, v. 1, p. 1-6, 2015. http://dx.doi.org/10.3395/2317-269x.00274

12. NOSANCHUK J ; NOSANCHUK M ; RODRIGUES M ; NIMRICHER L ; CAMPOS DE CARVALHO, ANTONIO C ; WEISS, LOUIS M. ;

SPRAY, DAVID C ; TANOWITZ, HERBERT B. . The Einstein-Brazil Fogarty: A decade of synergy. Brazilian Journal of Microbiology (Online) ,

v. 46, p. 945-955, 2015. http://dx.doi.org/10.1590/s1517-838246420140975

13. SONODA M ; DA SILVA R ; KMIT F ; ABRAHÃO M ; MONNERAT G ; VISCONDE BRASIL G ; MUZI-FILHO H ; SILVA PA ; TOVAR-

MOLL F ; VIEIRA A ; MEDEI, E. ; CARNEIRO-RAMOS M . Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-

Induced Cardiac Hypertrophy in Mice. Plos One , v. 10, p. e0139350, 2015. *IN COLLABORATION WITH TOVAR-MOLL (AL1)

14. SUHETT, G ; DE SOUZA, S. A. L. ; CARVALHO, A. B. ; RACHID, R. ; SILVA, NARCISA LEAL DA CUNHA E ; CAMPOS DE

CARVALHO, A. C. ; DA FONSECA, L. M. B. ; GOLDENBERG, R.C.S. ; GUTFILEN, BIANCA . 99m-Technetium binding site in bone marrow

mononuclear cells. Stem cell research & therapy, v. 6, p. 26041023, 2015 DOI: 10.1186/s13287-015-0107-0

15. VAIRO, L. ; MEDEI, E. H. ; SILVA dos SANTOS, D. ; GOLDENBERG, R. C. S. ; GOLDENBERG, RC. ; CAMPOS DE CARVALHO, A. C. .

Functional properties of a Brazilian derived mouse embryonic stem cell line. Anais da Academia Brasileira de Ciências (Impresso), v. 00, p. 00-00,

2015 DOI:10.1590/0001-3765201520140474


1. ASENSI, K. D. ; FORTUNATO, R. S. ; PACHECO, TS ; REZENDE, DF ; SILVA DOS SANTOS, D. ; RODRIGUES, D. C. ; KASAI-

BRUNSWICK, T. H. ; CAMPOS DE CARVALHO, A. C. ; CARVALHO, D. P. ; CARVALHO, A. B. ; GOLDENBERG, R. C. S. ;

GOLDENBERG, RC. . Reprogramming to a pluripotent state modifies mesenchymal stem cell resistance to oxidative stress. Journal of Cellular

and Molecular Medicine (Print), v. 1, p. n/a-n/a, 2014. DOI:10.1111/jcmm.12226

2. CHEUNG, K. ; MARQUES-DA-SILVA, C. ; VAIRO, L. ; SILVA dos SANTOS, D. ; GOLDENBERG, R. C. S. ; GOLDENBERG, RC. ;

COUTINHO-SILVA, C. ; BURNSTOCK, G. . Pharmacological and molecular characterization of functional P2 receptors in rat embryonic

cardiomyocytes. Purinergic Signalling (Print), p. 127-138, 2014. DOI:10.1007/s11302-014-9441-4

3. FIGUEIRA, MIRIAM FRANKENTHAL ; MONNERAT-CAHLI, GUSTAVO ; MEDEI, EMILIANO ; Carvalho, Adriana Bastos ; MORALES,

MARCELO MARCOS ; LAMAS, MARCELO EINICKER ; DA FONSECA, RODRIGO NUNES ; SOUZA-MENEZES, JACKSON .

MicroRNAs: potential therapeutic targets in diabetic complications of the cardiovascular and renal systems. Acta Physiologica (Print), v. 1, p. n/a-

n/a, 2014. DOI:10.1111/apha.12316

4. FIGUEIRA, MIRIAM FRANKENTHAL ; MONNERAT-CAHLI, GUSTAVO ; MEDEI, EMILIANO ; CARVALHO, ADRIANA BASTOS ;

MORALES, MARCELO MARCOS ; LAMAS, MARCELO EINICKER ; DA FONSECA, RODRIGO NUNES ; SOUZA-MENEZES, JACKSON

. MicroRNAs: potential therapeutic targets in diabetic complications of the cardiovascular and renal systems. Acta Physiologica (Print) , v. 6, p.

n/a-n/a, 2014.

5. HOSSNE, N. A. ; CRUZ, E. ; BUFFOLO, E. ; COIMBRA, A. C. T. S. M. D. ; MACHADO, J. ; GOLDENBERG, R. C. S. ; GOLDENBERG, RC.

; REGAZZI, G. ; AZEVEDO, S. ; INVITTI, A. L. ; BRANCO, J. N. R. ; OLIVEIRA, J. S. R. ; STOLF, N. A. G. ; MILLER, L. W. ; SANBERG, P.

R. . Long-term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT (Refractory Angina

Cell Therapy) Clinical Update. Cell Transplantation, v. 1, p. 24819720, 2014. DOI:10.3727/096368914X681595

6. MONNERAT G ; COUTINHO D ; FERREIRA A ; MEDEI, E. . Activation of angiotensin-converting enzyme 2 improves cardiac electrical

changes in ventricular repolarization in streptozotocin-induced hyperglycaemic rats. Europace (London, England) , v. 1, p. 10.1093, 2014.

7. MONNERAT-CAHLI, GUSTAVO ; TRENTIN-SONODA, MAYRA ; GUERRA, BÁRBARA ; MANSO, GABRIEL ; FERREIRA, ANDREA

C.F. ; SILVA, DIORNEY L.S.G. ; COUTINHO, DANIELLE C. ; CARNEIRO-RAMOS, MARCELA S. ; RODRIGUES, DEIVID C. ; CABRAL-

DA-SILVA, MAURICIO C. ; GOLDENBERG, REGINA C.S. ; NASCIMENTO, JOSÉ H.M. ; CAMPOS DE CARVALHO, ANTONIO C. ;


145

MEDEI, EMILIANO . Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats. International

Journal of Cardiology (Print), v. 171, p. 199-208, 2014. DOI:10.1016/j.ijcard.2013.12.013

8. MONNERAT-CAHLI, GUSTAVO ; ALONSO, HIART ; GALLEGO, MONICA ; ALARCÓN, MICAELA LOPEZ ; BASSANI, ROSANA A. ;

CASIS, OSCAR ; MEDEI, EMILIANO . Toll-like receptor 4 activation promotes cardiac arrhythmias by decreasing the transient outward

potassium current (Ito) through an IRF3-dependent and MyD88-independent pathway. Journal of Molecular and Cellular Cardiology , v. 76, p. 116-

125, 2014.

9. PASSIPIERI, J. A. ; BRUNSWICK, T. H. K. ; SUHETT, G.D. ; MARTINS, A. B. ; BRASIL, G. V. ; CAMPOS, D. B. ; ROCHA, NAZARETH N.

; RAMOS, I. P. ; Mello, D.B. ; RODRIGUES, D. C. ; CHRISTIE, B.B. ; Silva, BJ ; BALDUINO, A. ; SA, R. M. ; LOPES, L. M. ;

GOLDENBERG, RC. ; CAMPOS DE CARVALHO, A. C. ; CARVALHO, A. B. . Improvement of cardiac function by placenta-derived

mesenchymal stem cells does not require permanent engraftment and is independent of the insulin signaling pathway. Stem cell research & therapy,

v. 5, p. 102, 2014. DOI:10.1186/scrt490

10. SILVA DOS SANTOS, D. ; PINHO-RIBEIRO, VANESSA ; ASENSI, K. D. ; VAIRO, L. ; CARVALHO, A. B. ; CAMPOS-DE-CARVALHO,

A.C. ; GOLDENBERG, R. C. S. . Human Menstrual Blood Derived Mesenchymal Cells As New Human Feederlayer System For Human

Embryonic Stem Cells. Cell Medicine: Part B, p. 1-1, 2014. DOI:0.3727/215517913X679265

11. SILVA, FA ; RODRIGUES, D. C. ; VAIRO, L. ; DIAS, WB ; ASENSI, K. D. ; GOLDENBERG, R. C. S. ; URMENYI, T. P. ; TODESCHINI, AR

. Evidences for the involvement of cell surface glycans in stem cell pluripotency and differentiation. Glycobiology (Oxford), v. 24, p. 458-468,

2014. DOI:10.1093/glycob/cwu012

12. SILVA, JOHNATAS D. ; PAREDES, BRUNO D. ; ARAÚJO, INDIANARA M. ; LOPES-PACHECO, MIQUÉIAS ; OLIVEIRA, MILENA V. ;

SUHETT, GRAZIELLE D. ; FACCIOLI, LANUZA A. P. ; ASSIS, EDSON ; CASTRO-FARIA-NETO, HUGO C. ; GOLDENBERG, REGINA C.

S. ; CAPELOZZI, VERA L. ; MORALES, MARCELO M. ; PELOSI, PAOLO ; XISTO, DÉBORA G. ; ROCCO, PATRICIA R. M. . Effects of

Bone Marrow-Derived Mononuclear Cells From Healthy or Acute Respiratory Distress Syndrome Donors on Recipient Lung-Injured Mice. Critical

Care Medicine, v. 42, p. 1-524, 2014. DOI10.1097/CCM.0000000000000296

13. SILVA, P. A. ; MONNERAT-CAHLI, G. ; PEREIRA-ACACIO, A. ; LUZARDO, R. ; SAMPAIO, L. S. ; LUNA-LEITE, M. A. ; LARA, L. S. ;

EINICKER-LAMAS, M. ; PANIZZUTTI, R. ; MADEIRA, C. ; VIEIRA-FILHO, L. D. ; CASTRO-CHAVES, C. ; RIBEIRO, V. S. ; PAIXÃO, A.

D. O. ; MEDEI, E. ; VIEYRA, A . Mechanisms Involving Ang II and MAPK/ERK1/2 Signaling Pathways Underlie Cardiac and Renal Alterations

during Chronic Undernutrition. Plos One , v. 9, p. e100410, 2014. * IN COLLABORATION WITH VIEYRA (AL17)


1. GOLDENBERG, R. C. S.; CARVALHO, A. C. C. . Resident Stem Cells and Regenerative Therapy. 1. ed. Amsterdam: Elsevier, 2013. 251p

(BOOK).

2. MONNERAT-CAHLI, GUSTAVO ; TRENTIN-SONODA, MAYRA ; GUERRA, BÁRBARA ; MANSO, GABRIEL ; FERREIRA, ANDREA

C.F. ; SILVA, DIORNEY L.S.G. ; COUTINHO, DANIELLE C.; CARNEIRO-RAMOS, MARCELA S. ; RODRIGUES, DEIVID C. ; CABRAL-

DA-SILVA, MAURICIO C. ; GOLDENBERG, REGINA C.S. ; NASCIMENTO, JOSÉ H.M. ; CAMPOS DE CARVALHO, ANTONIO C. ;

MEDEI, EMILIANO . Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats. International

Journal of Cardiology (Print) , v. 171, p. 199-208, 2013.

3. QUINTANILHA, L. F. ; TAKAMI, T. ; HIROSE, Y. ; FUJISAWA, K. ; MURATA, Y. ; YAMAMOTO, N. ; GOLDENBERG, R. C. S. ; TERAI,

S. ; SAKAIDA, I. . Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injury in vitro and in vivo.

Hepatology Research (Print),, 2013. DOI:10.1111/hepr.12204

4. HADDAD, NF ; TEODORO, AJ ; LEITE, F. O. ; SOARES, N. ; MATTOS, RM ; HECHT, F. ; DEZONNE, R. ; VAIRO, LEANDRO ;

GOLDENBERG, R. C. S. ; ALCANTARA, F. G. ; CARVALHO, D. P. ; GADELHA, M. R. ; NASCIUTTI, LE ; ALVES, LM . Lycopene and

Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells. Plos One, v. 8, p. e62773, 2013.

DOI:10.1371/journal.pone.0062773

5. MARON-GUTIERREZ T ; SILVA, JD ; ASENSI, K. D. ; BAKKER-ABREU, I ; SHAN, Y. ; DIAZ, BL ; GOLDENBERG, R. C. S. ;

GOLDENBERG, RC. ; MEI, S. H. ; STEWART, D. J. ; MORALES, MARCELO MARCOS ; PATRICIA RIEKEN MACEDO ROCCO ;

SANTOS, C. . Effects of Mesenchymal Stem Cell Therapy on the Time Course of Pulmonary Remodeling Depend on the Etiology of Lung Injury

in Mice. Critical Care Medicine, v. 41, p. 319-333, 2013. DOI:10.1097/CCM.0b013e31828a663e

6. CASTRO, P. H. R. ; SCHMIDT, F. R. ; BATTISTELLA, V. ; DE SOUZA, S. A. L. ; GUTFILEN, BIANCA ; GOLDENBERG, R. C. S. ;

GOLDENBERG, RC. ; KASAI-BRUNSWICK, T. H. ; VAIRO, L. ; SILVA RM ; WAJNBERG, E. ; BRASIL, P. E. A. A. ; GASPARETTO ;

MAIOLINO A ; ALVES-LEON, S. V. ; ANDRE, C. ; MENDEZ-OTERO, R. ; DE FREITAS, G. R. ; DA FONSECA, L. M. B. . Biodistribution

of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. Regenerative Medicine (Print), v. 8,

p. 145-155, 2013 DOI:10.2217/rme.13.2 *IN COLLABORATION WITH MENDEZ-OTERO (AL19).

7. TAKIYA, C.M. ; PAREDES, BRUNO DIAZ ; QUINTANILHA, L. F. ; DIAS, GS ; FACCIOLI, L. A. P. ; TAKAMI, T. ; TERAI, S. ; SAKAIDA,

I. ; GOLDENBERG, R. C. S. ; GOLDENBERG, RC. . Liver Resident Stem Cells. In: Regina Coeli dos Santos Goldenberg, Antonio Carlos

Campos de Carvalho. (Org.). Resident Stem Cells and Regenerative Theraphy. 1ed.Oxford, UK: Academic Press, 2013, v. 1, p. 177-203. (BOOK).

146


146

AL 17.- Associated Laboratory of Ion transport

physiology in health and disease

- Coodinator:

Adalberto Ramón Vieyra – Instituto de Biofísica Carlos Chagas Filho/UFRJ

- Researchers from national institutions: Aloa Machado de Souza – Faculdade de farmácia/UFRJ

Ana Acácia Pinheiro Caruso Neves – Instituto de Biofísica Carlos Chagas Filho/UFRJ

Ana Durce Oliveira da Paixão – Centro de Ciências Biológicas/UFPE

Celso Caruso Neves – Instituto de Biofísica Carlos Chagas Filho/UFRJ

Federica Collino – Instituto de Biofísica Carlos Chagas Filho/UFRJ

Jennifer Lowe – Instituto de Biofísica Carlos Chagas Filho/UFRJ

José Roberto Meyer Fernandes – Instituto de Bioquímica Médica Leopoldo de Meis/UFRJ

Leucio Duarte Vieira Filho – Centro de Ciências Biológicas/UFPE

Lucienne da Silva Lara – Instituto de Ciências Biomédicas/UFRJ

Luiz Roberto Leão Ferreira – Instituto de Biologia/UFF

Marcelo Einicker Lamas – Instituto de Biofísica Carlos Chagas Filho/UFRJ

Marcos Romualdo Costa – Instituto do Cérebro/UFRN

Rafael Soares Lindoso – Instituto de Biofísica Carlos Chagas Filho/UFRJ

Rafael Valverde – Instituto de Biofísica Carlos Chagas Filho/UFRJ

- Collaborators from international

institutions:

Elisabeth Mintz – CEA, BIG-LCBM,

CNRS, BIG-LCBM and Université

Grenoble Alpes, BIG-LCBM, Grenoble,

France

Giovanni Camussi – Translational Center of

Regenerative Medicine Unito/Fresenius

Medical Care, Torino, Italy

Martine Cuillel – CEA, BIG-LCBM,

CNRS, BIG-LCBM and Université

Grenoble Alpes, BIG-LCBM, Grenoble,

France

Minolfa Prieto – Department of Physiology,

Tulane University School of Medicine,

New Orleans, USA

Oliver Wessely – Lerner Research Institute

- Cleveland Clinic, Cleveland, Ohio, USA.

Vincenzo di Marzo – Director, Istituto di

Chimica Biomolecolare (ICB), Consiglio

Nazionale delle Ricerche (CNR), Napoli,

Italy.


Aline Marie Fernandes (IBCCF /UFRJ);

André Luiz Araujo dos Santos

(IIBqM/UFRJ);

- Postdoctoral fellows (continuing):

Clara Rodrigues Ferreira (IBCCF /UFRJ);

Claudia F Dick (IBCCF /UFRJ);

Gomes (IBqM/UFRJ);

Daniela Cosentino Gomes (IBqM/UFRJ);

Diogo de Barros Peruchetti (UFRJ);

Edjair Vicente Cabral (UFPE);

Eduardo Bouth Sequerra (UFRN);

Giovane Gomes Tortelote (IBCCF /UFRJ

);

Hellen JV Beiral (IBCCF /UFRJ);

Humberto Muzi Filho (IBCCF /UFRJ);

João Luiz da Silva Filho (UFRJ);

Karine da Silva Verdoorn (IBCCF /UFRJ);

Leandro de Souza Silva (UFRJ);

Lindalva L Malagueta Vieira (Universidad

del Pais Vasco, EHU, Espanha);

Lisvane Paes Vieira (IBqM/UFRJ);

Luiza Villarinho Prereira Mendes (UFRJ);

Luzia da Silva Sampaio (IBCCF /UFRJ);

Michelle Tanny Cunha do Nascimento

(IBqM/UFRJ);

Naira L Giarola (IBqM/UFRJ);

Paulo André da Silva (IBCCF /UFRJ);

Rosilane Taveira da Silva (UFRJ);

Thaís Russo Abrahão (IBqM/UFRJ);

Thiago Pereira de Abreu (UFRJ).

147


147


Andreson Charles de Freitas Silva (UECE);

Anita Leocádio Freitas Mesquita

(IBqM/UFRJ); Bruna Soares Landeira

(UFRN); Cintia Giselle Martins Ferreira

(UFRPE); Daniela Maria de Sousa Moura

(UFRN); Dayana de Souza Freire (UFRJ);

Jéssica Alves de Medeiros Araújo (UFRN);

Juliana Alves Brandão (UFRN); Juliane -

Lopes de Assis (UFRJ);

Juliane Silva de Farias (UFPE);

Julliana Ferreira Sant´Anna (UFRJ);

Laíse de Souza Elias (UFRPE);

Luis Gustavo Farias de Sousa (UECE);

Luiz Fernando Carvalho Kelly (IBqM/

UFRJ);

Luiza Helena Daltro Cardoso (UFRJ);

Nathalia Rocco Machado (IBqM/UFRJ);

Paula Mattos da Silva (UFRJ);

Paula Viegas Signoretti (UFRJ);

Rafael Luzes Pereira (Unigranrio /Inmetro/

Uezo);

Regina Souza Aires (UFPE);

Sabrina Ribeiro Gonsalez (UFRJ);

Thiago Pereira da Silva (UFRJ).


Alana Carolina Costa Veras (UFPE);

Aline Leal Cortes (UFRJ);

Amanda Durval Zeferino da Silva (IBqM/

UFRJ);

Amaury Pereira Acácio (IBqM/UFRJ);

Ayra Diandra Carvalho de Araújo (IMPPG/

UFRJ);

Danielle Guedes Dantas Lira (UFPE);

Edgleyson Chaves dos Santos (UECE);

Jaíne Quinze Dias Barroso de Oliveira

(UFRJ);

Juliana Paiva (IBCCF/UFRJ);

Luiz Filipe Nossar Freire Vital Prisco

(IBCCF/UFRJ);

- Master's students (continuing):

Marco Antonio Lacerda Abreu (IBqM/

UFRJ);

Raquel Costa da Silva (UFRJ);

Thayná da Silva Constantino (UFPE);

Wilka Rosane de Araújo Farias (UFPE).


Bárbara da Silva Aniceto (UERJ);

Bruna Aparecida Bernardes (UFRJ);

Bruna Stephannie Nascimento Ferreira

(IBCCF/UFRJ);

Cinthya Rodrigues (UNIRIO);

Clarissa Carvalho da Motta (UFRJ);

Crisllaine da Cunha Pereira (UFRN);

Dayene Santos Gomes (UFRJ);

Douglas Esteves Teixeira (UFRJ);

Gabriela Batista Oliveira da Silva (UFRJ);

Gabriella Marques Siqueira (UFRJ);

Giovana Fonseca (UFRJ);

Gisele Araújo Rodrigues (UFPE);

Herica Monteiro da Silva (UFRJ);

Jarlene Alécia Lopes (IBCCF/UFRJ);

Laryssa Beatriz Silva Nascimento (UFPE);

Linaldo Francisco da Silva Filho (UFPE);

Luciana Venezziani (IFRJ);

Maicon Landim Vieira (IBCCF /UFRJ);

Miguel Zidan (UFRJ);

Natália Kryzia dos Santos Lima (UFPE);

Natalia Larissa Martins Lisbôa (UFRJ);

Nathalia Cristina Ferreira Bezerra (UFRJ);

Rodrigo Pacheco da Silva de Aguiar

(UFRJ);

Sarana Alves Barros (IBCCF /UFRJ);

Vitoria Gomes Bochner (UFRJ).

- Technicians:

Celso Pereira (IBCCF /UFRJ);

Glória Costa Sarmento (IBCCF /UFRJ);

Rosilane Taveira da Silva (IBCCF /UFRJ).

148


148

The global aim of Laboratory 17 is to study

kinetics, mechanisms and regulation of ion

transport in physiological and pathological

conditions using mammal cells (from

kidney and liver) and parasite cells (mainly

trypanosomatids).

In projects related with ion transport in

kidney, the main achievements in the period

2013-2016 were unraveling cellular and

molecular events related with the

renin/angiotensin/aldosterone system and

its influence in sodium and water transport.

Identification of regulatory sites targeted by

different kinases acting in different network

wiring.

Through an association with the UFPE

group, we were able to identify that an

altered signaling linked to angiotensin II

(Ang II) could be associated with increased

Na+ reabsorption in renal proximal tubules

during chronic undernutrition. These

findings shed light on the mechanisms by

which altered Ang II-associated pathways

can lead to profound modification in the

kinetics and regulation of the renal

proximal tubule Na+-ATPase in chronically

undernourished rats (Figure 1). We propose

that these modifications are key in the

development of renal lesions and

hypertension in countries and regions where

food supply is chronically scarce

Figure 1 - Functional domains of Na+-ATPase that could be potentially regulated by PKC- and PKA-mediated

phosphorylations. (A) The illustration presents the 3D modeled structure of the ATNA (Na+-ATPase) active

site from Cavia Porcellus, in which the predicted nucleotide, kinase and phosphatase domains of the pump are

indicated. The sequence was aligned with the crystalline structure of the nucleotide-binding domain from rat

(Na+ + K+)ATPase α1-subunit. Relevant amino acids in these motifs and the postulated Na+-binding site I

(Glu322) are highlighted. Reproduced with permission from. (B) Predicted 3D structure using the ATNA

sequence and the crystalline structure of wild porcine (Na+ + K+) ATPase α1-subunit resolved in a stable

analog of the transition state E1 ~ P · ADP · 3Na+. Yellow: motifs involved in nucleotide binding. Red:

phosphatase domain. Orange: cation-binding motif in the M4 transmembrane segment. Dark blue: kinase

domain. Green: potentially PKC-phosphorylatable Thr333 and Thr636. Light blue: possible site (Ser462) for

PKA. Thr54 and Thr81 are not represented because the modeling does not cover the N-terminal region. The

green arrow points to the Thr333 residue, which is hidden in the tridimensional representation.

149


149

The laboratory also obtained significant

advances in the field of the mechanism of

repair promoted by stem cells in metabolic

and transport processes impaired in

prevalent pathologies such as acute kidney

injury. Proteomic studies using label free

EM allowed to identify processes and

mechanisms affected and how recovery can

occur and what is the role of microRNAs

and extracellular vesicles secreted, for

example, by mesenchymal cells.

We were able to identify signaling

networks and key proteins involved in the

repair of ischemia by mesenchymal stromal

cells (MSC). Using an in vitro model of

Acute kidney injury (AKI) to investigate

paracrine interactions and label-free high

definition 2D-NanoESI-MSE, differentially

expressed proteins were identified in a

human renal proximal tubule cell lineage

(HK-2) exposed to human MSC (hMSC)

after an ischemic insult. In silico analysis

showed that hMSC stimulated antiapoptotic

activity, normal ROS handling, energy

production, cytoskeleton organization,

protein synthesis, and cell proliferation. The

proteomic data were validated by parallel

experiments demonstrating reduced

apoptosis in HK-2 cells and recovery of

intracellular ATP levels. qRT-PCR for

proteins implicated in the above processes

revealed that hMSC exerted their effects by

stimulating translation, not transcription.

Western blotting of proteins associated with

reactive oxygen species (ROS) and energy

metabolism confirmed their higher

abundance in HK-2 cells exposed to hMSC.

Taken as a whole, these findings suggest

that the effect of hMSC on renal cells is

mediated mainly by the induction of protein

translation—from the mRNA accumulated

during anoxia— rather than transcription, a

process made feasible by a parallel

enhancement of ATP synthesis. The large-

scale shotgun proteomic approach provides

a comprehensive view of events in injured

renal cells during their interaction with

human mesenchymal stromal cells (hMSC),

providing new insights into the molecular

mechanisms involved.

Fourthermore, during the last 4 years, the

Laboratory also has developed internal

collaborations and interactions with

researchers from Laboratories 1, 2, 4, 7, 9,

11, 12 and 16 of the INBEB (See the list of

publications below).

Our partnership with Laboratory 16 has

enabled us to elucidate that AMPK

activation and ROS neutralization are key

strategies to induce tolerance to Chagas

heart disease. Despite all tissue damage

observed in established Chagas heart

disease, we found that a physiological

dysfunction can still be reversed by

treatment with resveratrol, metformin and

tempol, resulting in improved heart

function and representing a starting point to

develop innovative therapies in Chronic

chagasic cardiomyopathy.

In another paper, which had the

collaboration of AL 16 (Professor Emiliano

Medei - UFRJ) and AL 1 (Professor

Fernanda Tova-Moll – IDOR/UFRJ), we

investigated whether the pathways linked to

Toll-like receptors 2 and 4 (TLRs) are

involved in renal ischemia-reperfusion

(I/R)-induced cardiac hypertrophy. We

conclude: (i) TLRs are involved in renal

I/R-induced cardiac hypertrophy; (ii)

absence of TLRs prevents I/R-induced

cardiac hypertrophy, despite renal lesions

seeming to evolve towards those of chronic

disease; (iii) TLR2 and TLR4 selectively

regulate the systemic inflammatory profile

and NF- κB activation.

The Collaboration with Laboratory 2

(Professor Martha Sorenson – UFRJ) has

enabled us to demonstrate some key

findings that shed light on the mechanisms

that explain, at the mitochondrial level, how

stem cells prevent damage by

ischemia/reperfusion. The action of BMSCs

on mitochondrial functions raises the

possibility that autologous bone marrow

stem cells may help prevent

ischemia/reperfusion injuries associated

with transplantation and acute renal

diseases.

All these contributions involve several

graduate and undergraduate students, as

well as post-doctoral trainees.

150


150


1. ARAUJO, G.L. ; VIEIRA, A.E.D. ; BARREIRO, E.J. ; LIMA, L.M. ; CARDOSO, C.N. ; EMILIANO, N.F. ; MARTINS, M.T. ; SOUZA,

S.S. ; DE SOUZA, A.M. ; BERTO, C. ; COSTA, M.L. ; CAMPOS, L.M. ; FRANÇA, F.D. ; TAGLIATI, C.A. . Toxicological in vitro and

subchronic evaluation of LASSBio-596. Food and Chemical Toxicology, p. 148-156, 2014. http://dx.doi.org/10.1016/j.fct.2014.07.037

2. ARGOLO, A. ; DANTAS, V. ; SATURNINO, A. ; SANTOS, A. ; BRANDÃO-NETO, J. ; PAIXÃO, A. ; COELHO, L. . Leaf Ethanolic

Extract of Bauhinia monandra Increases Insulin Secretion in Rats Subjected to Intrauterine Malnutrition. International Journal of

Biochemistry Research & Review, v. 9, p. 1-9, 2016. http://dx.doi.org/10.9734/ijbcrr/2016/22434

3. ARNAUD-BATISTA, FRANCISCO J. ; PERUCHETTI, DIOGO B. ; ABREU, THIAGO P. ; DO NASCIMENTO, NILBERTO R.F. ;

MALNIC, GERHARD ; FONTELES, MANASSES C. ; CARUSO-NEVES, CELSO . Uroguanylin modulates (Na++K+)ATPase in a

proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase a, and mTOR pathways. Biochimica et

Biophysica Acta. G, General Subjects (Print), v. 1860, p. 1431-1438, 2016. http://dx.doi.org/10.1016/j.bbagen.2016.04.012

4. CORNELIO, A. M. ; BITTENCOURT-NAVARRETE, R. E. ; BITTENCOURT BRUM, R. ; QUEIROZ, C. M. ; COSTA, M. R. . Human

Brain Expansion during Evolution Is Independent of Fire Control and Cooking. Frontiers in Neuroscience, v. 10, p. 1-11, 2016.

http://dx.doi.org/10.3389/fnins.2016.00167

5. DE SOUZA SILVA, LEANDRO ; DE BARROS PERUCHETTI, DIOGO ; SILVA, CLAUDIO TEIXEIRA FERREIRA-DA ;

TEIXEIRA-FERREIRA, ANDRÉ ; PERALES, JONAS ; CARUSO-NEVES, CELSO ; PINHEIRO, ANA ACACIA SÁ . Interaction

between bradykinin B2 and Ang-(1-7) Mas receptors regulates erythrocyte invasion by Plasmodium falciparum. Biochimica et Biophysica

Acta. G, General Subjects (Print), v. 1, p. 1-5, 2016. http://dx.doi.org/10.1016/j.bbagen.2016.07.011

6. DOS SANTOS A. L. A ; DICK, C. F. ; CARVALHO-KELLY, L. F. ; MEYER-FERNANDES, JR . Innate immunomodulation to

trypanosomatid parasite infections. Experimental Parasitology, v. 167, p. 67-75, 2016. http://dx.doi.org/10.1016/j.exppara.2016.05.005

7. FREITAS-MESQUITA, A. L. ; GOMES, MARTA T. ; VIEIRA DP ; VIEIRA, L. P. ; NASCIMENTO, M. C. ; LOPES, ANGELA H. S.

C. ; MEYER-FERNANDES, JOSÉ ROBERTO . Inhibitory effects promoted by 5 -nucleotides on the ecto-3 -nucleotidase activity of

Leishmania amazonensis. Experimental Parasitology, v. 169, p. 111-118, 2016. http://dx.doi.org/10.1016/j.exppara.2016.08.001

8. HILÁRIO-SOUZA, E. ; CUILLEL, M. ; MINTZ, E. ; CHARBONNIER, P. ; VIEYRA, A. ; CASSIO, D. ; LOWE, J. . Modulation of

hepatic copper-ATPase activity by insulin and glucagon involves protein kinase A (PKA) signaling pathway. Biochimica et Biophysica

Acta. Molecular Basis of Disease, v. 1862, p. 2086-2097, 2016. http://dx.doi.org/10.1016/j.bbadis.2016.08.008

9. LANDEIRA, BRUNA SOARES ; SANTANA, THEMIS TAYNAH DA SILVA ; ARAÚJO, JÉSSICA ALVES DE MEDEIROS ;

TABET, ELIE I. ; TANNOUS, BAKHOS A. ; Schroeder, Timm ; Costa, Marcos R. . Activity-Independent Effects of CREB on Neuronal

Survival and Differentiation during Mouse Cerebral Cortex Development. Cerebral Cortex (New York, N.Y. 1991), v. 27, p. 1, 2016.

http://dx.doi.org/10.1093/cercor/bhw387

10. LINDOSO, RAFAEL S. ; SANDIM, VANESSA ; COLLINO, FEDERICA ; CARVALHO, ADRIANA B. ; DIAS, JULIANA ; DA

COSTA, MILENE R. ; ZINGALI, RUSSOLINA B*. ; VIEYRA, ADALBERTO . Proteomics of cell-cell interactions in health and

disease. Proteomics (Weinheim. Print), v. 16, p. 328-344, 2016. http://dx.doi.org/10.1002/pmic.201500341 *IN COLLABORATION

WITH ZINGALI (AL 4)

11. LOPES DE ASSIS, JULIANE ; GROBAS, IAGO L. ; PEREIRA SIGNORETTI, PAULA VIEGAS ; MARIE FERNANDES, ALINE ;

CARVALHO MIRANDA, MARIA ADELAIDE ; SILVA, BRUNO F.B. ; FELIPPE VALVERDE, RAFAEL HOSPODAR ; EINICKER-

LAMAS, MARCELO ; DE BEULE, PIETER A.A. . Lipoplexes for Gene Delivery Characterized by Fluorescence Correlation

Spectroscopy. Biophysical Journal (Print), v. 110, p. 489a-490a, 2016. http://dx.doi.org/10.1016/j.bpj.2015.11.2617

12. OLIVEIRA, S. D. A. S. ; OLIVEIRA2, N. F. ; MEYER-FERNANDES, JOSÉ ROBERTO ; SAVIO, E. B. ; ORNELAS, F. G. I. ;

FERREIRA, Z. S. ; COUTINHO-SILVA, R. ; SILVA, C. L. M. . Increased expression of NTPDases 2 and 3 in mesenteric endothelial

cells during schistosomiasis favors leukocyte adhesion through P2Y1 receptors. Vascular Pharmacology, v. 82, p. 66-72, 2016.

http://dx.doi.org/10.1016/j.vph.2016.02.005

13. ORTEGA, FELIPE ; COSTA, MARCOS R. . Live Imaging of Adult Neural Stem Cells in Rodents. Frontiers in Neuroscience, v. 10, p.

78, 2016. http://dx.doi.org/10.3389/fnins.2016.00078

14. RIBEIRO, NATALIE E. ; CABRAL, E.V. ; AIRES, REGINA S. ; VIEIRA-FILHO, LEUCIO D. ; RIBEIRO, VALDILENE S. ;

GONÇALVES, DAIANNA R.M. ; BORGES, LUIS P.N.C. ; MELO, ISMAELA M. F. ; FERREIRA, CINTIA G. M. ; WANDERLEY-

TEIXEIRA, VALERIA ; TEIXEIRA, ÁLVARO A. C. ; SOARES, ANÍSIO F. ; Paixão, Ana D.O. . Maternal Na intake induces renal

function injury in rats prevented by a short-term angiotensin converting enzyme inhibitor. Clinical and Experimental Pharmacology &

Physiology, v. 1, p. 1-8-8, 2016. http://dx.doi.org/10.1111/1440-1681.12702

15. RODRIGUES, LISA ; RUSSO-ABRAHÃO, THAIS ; CUNHA, RODRIGO A. ; GONÇALVES, TERESA ; MEYER-FERNANDES,

JOSÉ ROBERTO . Characterisation of extracellular nucleotide metabolism in Candida albicans. FEMS Microbiology Letters, v. 363, p.

fnv212, 2016. http://dx.doi.org/10.1093/femsle/fnv212

16. SATHLER, MATHEUS FIGUEIREDO ; STUTZ, BERNARDO ; MARTINS, ROBERTTA SILVA ; DOS SANTOS PEREIRA,

MAURÍCIO ; PECINALLI, NEY RONER ; SANTOS, LUIS E. ; TAVEIRA-DA-SILVA, ROSILANE ; LOWE, JENNIFER ; DE

FREITAS, ISIS GRIGORIO ; DE MELO REIS, RICARDO AUGUSTO ; MANHÃES, ALEX C. ; KUBRUSLY, REGINA C.C. . Single

exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms. Neuroscience, v.

329, p. 326-336, 2016. http://dx.doi.org/10.1016/j.neuroscience.2016.05.022

17. SILVA, ADRIANA F. ; OLIVEIRA, VANI X. ; SILVA, LEANDRO S. ; PINHEIRO, ANA A.S. ; CISCATO, LUIZ F.M.L. .

Antiplasmodial activity of alkyl-substituted 1,2-dioxetanes against Plasmodium falciparum. Bioorganic & Medicinal Chemistry Letters

(Print), v. 000, p. 000-000, 2016. http://dx.doi.org/10.1016/j.bmcl.2016.08.096

18. SILVA, JOHNATAS DUTRA ; DE OLIVEIRA, GISELE PENA ; SAMARY, CYNTHIA DOS SANTOS ; ARAUJO, CARLA

CRISTINA ; PADILHA, GISELE DE ARAUJO ; E SILVA FILHO, FERNANDO COSTA ; DA SILVA, ROSILANE TAVEIRA ;

EINICKER-LAMAS, MARCELO ; MORALES, MARCELO MARCOS ; CAPELOZZI, VERA LUIZA ; DA SILVA, VANESSA

MARTINS ; LIMA, L'DIA MOREIRA ; BARREIRO, ELIEZER JESUS ; DIAZ, BRUNO LOUREN'O ; PELOSI, PAOLO ; SILVA,

PEDRO LEME ; GARCIA, CRISTIANE SOUZA NASCIMENTO BAEZ ; ROCCO, PATRICIA RIEKEN MACEDO . Respiratory and

Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome. Cellular Physiology and

Biochemistry, v. 38, p. 821-835, 2016. http://dx.doi.org/10.1159/000443037

19. SILVA, L. S. ; PERUCHETTI, D. B. ; FERREIRA, C. T. S. ; TEIXEIRA-FERREIRA, A. ; PERALES, J. ; CARUSO-NEVES, C. ;

PINHEIRO, A. A. S. . Interaction between bradykinin B2 and Ang-(1-7) Mas receptors regulates erythrocyte invasion by Plasmodium

falciparum. Biochimica et Biophysica Acta. G, General Subjects (Print), 2016.

20. SILVA, LEANDRO S. ; SILVA-FILHO, JOÃO LUIZ ; CARUSO-NEVES, CELSO ; PINHEIRO, ANA ACACIA S. . New Concepts in

Malaria Pathogenesis: The Role of the Renin-Angiotensin System. Frontiers in Cellular and Infection Microbiology, v. 5, p. 103, 2016.

http://dx.doi.org/10.3389/fcimb.2015.00103

21. SILVA-FILHO, JOÃO LUIZ ; CARUSO-NEVES, CELSO ; PINHEIRO, ANA ACACIA SÁ . Angiotensin II type-1 receptor (AT1R)

regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells. Scientific Reports, v. 6, p. 35997, 2016.


22. SILVA-FILHO, JOÃO LUIZ ; PERUCHETTI, DIOGO BARROS ; MORAES-SANTOS, FELIPE ; LANDGRAF, SHARON

SCHILLING ; SILVA, LEANDRO SOUZA ; SIRTOLI, GABRIELA MODENESI ; ZAMITH-MIRANDA, DANIEL ; TAKIYA,

CHRISTINA MAEDA ; PINHEIRO, ANA ACACIA SÁ ; DIAZ, BRUNO LOURENÇO ; CARUSO-NEVES, CELSO . Group V

Secretory Phospholipase A2 Is Involved in Tubular Integrity and Sodium Handling in the Kidney. Plos One, v. 11, p. e0147785, 2016.


23. VIEYRA, ADALBERTO; SILVA, PAULO A. ; MUZI-FILHO, HUMBERTO ; DICK, CLAUDIA F. ; ARAUJO-DOS-SANTOS,

ANDRÉ L. ; DIAS, JULIANA ; VIEIRA-FILHO, LEUCIO D. ; PAIXÃO, ANA D. O. . The Role of the Second Na+ Pump in Mammals

and Parasites. In: Sajal Chakraborti; Naranjan S. Dhalla. (Org.). Regulation of Membrane Na+-K+ ATPase. 1ed.Winnipeg, Manitoba,

Canada: Springer International Publishing, 2016, v. 15, p. 93-112. [BOOK CHAPTER]

24. VILAR-PEREIRA, G. ; CARNEIRO, V. C. ; MATA-SANTOS, H. N. ; VICENTINO, A. R. R. ; RAMOS, I. P. ; GIAROLA, NAIRA

LIGIA LIMA ; FEIJO, D. F. ; MEYER-FERNANDES, JOSÉ ROBERTO ; PAULA-NETO, ; MEDEI, E. H*. ; BOZZA, M. T. ;

151


151

LANNES-VIEIRA, J. ; PAIVA, C. N. . Resveratrol Reverses Functional Chagas Heart Disease in Mice. PLoS Pathogens (Online), v. 12,

p. e1005947, 2016. http://dx.doi.org/10.1371/journal.ppat.1005947 *IN COLLABORATION WITH MEDEI (AL 16)

25. WEN, S ; DOONER, M ; CHENG, Y ; PAPA, E ; DEL TATTO, M ; PEREIRA, M ; DENG, Y ; GOLDBERG, L ; ALIOTTA, J ;

CHATTERJEE, D ; STEWART, C ; CARPANETTO, A ; COLLINO, F ; BRUNO, S ; CAMUSSI, G ; QUESENBERRY, P .

Mesenchymal stromal cell-derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells. Leukemia, v. 00,

p. 000, 2016. http://dx.doi.org/10.1038/leu.2016.107


1. ANOMAL, RENATA FIGUEIREDO ; DE VILLERS-SIDANI, ETIENNE ; BRANDÃO, JULIANA ALVES ; DINIZ, REBECCA ;

COSTA, MARCOS R. ; ROMCY-PEREIRA, RODRIGO N. . Impaired Processing in the Primary Auditory Cortex of an Animal Model

of Autism. Frontiers in Systems Neuroscience, v. 9, p. 1-12, 2015. http://dx.doi.org/10.3389/fnsys.2015.00158

2. COLLINO, F.; BRUNO, S. ; INCARNATO, D. ; DETTORI, D. ; NERI, F. ; PROVERO, P. ; POMATTO, M. ; OLIVIERO, S. ; TETTA,

C. ; QUESENBERRY, P. J. ; CAMUSSI, G. . AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles

Carrying MicroRNAs. Journal of the American Society of Nephrology, v. 26, p. 2349-2360, 2015.

http://dx.doi.org/10.1681/ASN.2014070710

3. COSTA, M. R.; HEDIN-PEREIRA, C. ; ROUAUX, C. . Progenitor diversity and neural cell specification in the central nervous system. 1.

ed. , 2015. 109p .[BOOK]

4. COSTA, MARCOS R.; MÃLLER, ULRICH . Specification of excitatory neurons in the developing cerebral cortex: progenitor diversity

and environmental influences. Frontiers in Cellular Neuroscience, v. 8, p. 1-9, 2015. http://dx.doi.org/10.3389/fncel.2014.00449

5. DE AZEVEDO-MARTINS, ALLAN C ; ALVES, JOÃO MP ; GARCIA DE MELLO, FERNANDO ; VASCONCELOS, ANA TEREZA

R ; DE SOUZA, WANDERLEY* ; EINICKER-LAMAS, MARCELO ; MOTTA, MARIA CRISTINA M . Biochemical and

phylogenetic analyses of phosphatidylinositol production in Angomonas deanei, an endosymbiont-harboring trypanosomatid. Parasites &

Vectors, v. 8, p. 1-12, 2015. http://dx.doi.org/10.1186/s13071-015-0854-x *IN COLLABORATION WITH DE SOUZA (AL 9).

6. FREITAS, E. O. ; NICO, D. ; GUAN, R. ; MEYER-FERNANDES, J.R. ; CLINCH, K. ; EVANS, G. B. ; TYLER, P. C. ; SCHRAMM, V.

L. ; PALATNIK-DE-SOUSA, C. B. . Immucillins Impair Leishmania (L.) infantum chagasi and Leishmania (L.) amazonensis

Multiplication In Vitro.. Plos One, v. 10, p. e0124183, 2015. http://dx.doi.org/10.1371/journal.pone.0124183

7. GEORGE, JIMMY ; GONÇALVES, FRANCISCO Q. ; CRISTÓVÃO, GONÇALO ; RODRIGUES, LISA ; MEYER FERNANDES,

JOSÉ ROBERTO ; GONÇALVES, TERESA ; CUNHA, RODRIGO A. ; GOMES, CATARINA A. . Different danger signals differently

impact on microglial proliferation through alterations of ATP release and extracellular metabolism. GLIA (New York, N.Y. : Print), v. 63,

p. 1636-1645, 2015. http://dx.doi.org/10.1002/glia.22833

8. GONZALEZ, ALEXIS A. ; LIU, LIU ; LARA, LUCIENNE S. ; BOURGEOIS, CAMILLE R.T. ; IBACETA-GONZALEZ, CRISTOBAL

; SALINAS-PARRA, NICOLAS ; GOGULAMUDI, VENKATESWARA R ; SETH, DALE M ; PRIETO, MINOLFA C. . PKCα-

dependent augmentation of cAMP and CREB phosphorylation mediates the angiotensin II stimulation of renin in the collecting duct.

American Journal of Physiology. Renal Physiology, v. 309, p. 880-888, 2015. http://dx.doi.org/10.1152/ajprenal.00155.2015

9. LINDOSO, RAFAEL SOARES ; COLLINO, FEDERICA ; CAMUSSI, GIOVANNI . Extracellular vesicles derived from renal cancer

stem cells induce a pro-tumorigenic phenotype in mesenchymal stromal cells. OncoTarget, v. 6, p. 7959-7969, 2015.

http://dx.doi.org/10.18632/oncotarget.3503

10. LOPES, NICOLAS S. ; YOSHITAKE, ARIANE M. ; SILVA, ADRIANA F. ; OLIVEIRA, VANI X. ; SILVA, LEANDRO S. ;

PINHEIRO, ANA A. S. ; CISCATO, LUIZ FRANCISCO M. L. . Antimalarial Effect of 3-Methoxy-1,2-Dioxetanes on the Erythrocytic

Cycle of. Chemical Biology & Drug Design (Print), v. 000, p. n/a-n/a, 2015. http://dx.doi.org/10.1111/cbdd.12599

11. MELO, S. ; BARAUNA, V. G. ; NEVES, V. J. ; FERNANDES, T. ; LARA, L. S., LARA L. da S. ; MAZZOTI, D. R. ; OLIVEIRA, E.

M. . Exercise training restores the cardiac microRNA-1 and -214 levels regulating Ca2+ handling after myocardial infarction. BMC

Cardiovascular Disorders (Online), v. 15, p. 166-174, 2015.

12. MEYER, A. ; EARP, A. C. S. ; VIEYRA, A . Dance and science: the role of intermediatic poetic movement as a pathway for scientific

divulgation in the contemporary arts realm. International Journal of Humanities and Social Science, v. 5, p. 28-36, 2015.

13. MUZI'FILHO, HUMBERTO ; SOUZA, ALESSANDRO M. ; BEZERRA, CAMILA G. P. ; BOLDRINI, LEONARDO C. ; TAKIYA,

CHRISTINA M. ; OLIVEIRA, FELIPE L. ; NESI, RENATA T. ; VALENÇA, SAMUEL S. ; SILVA, ANANSSA M. S. ;

ZAPATA'SUDO, GISELE ; SUDO, ROBERTO T. ; EINICKER'LAMAS, MARCELO ; VIEYRA, ADALBERTO ; LARA, LUCIENNE

S. ; CUNHA, VALERIA M. N. . Rats undernourished in utero have altered Ca 2+ signaling and reduced fertility in adulthood.

Physiological Reports, v. 3, p. e12587, 2015. http://dx.doi.org/10.14814/phy2.12587

14. ROCCO-MACHADO, N. ; COSENTINO-GOMES, D. ; MEYER-FERNANDES, J.R. . Modulation of Na+/K+ ATPase Activity by

Hydrogen Peroxide Generated through Heme in L. amazonensis. Plos One, v. 10, p. e0129604, 2015.


15. ROUAUX, CAROLINE ; HEDIN-PEREIRA, CECÍLIA ; COSTA, MARCOS R. . Editorial: Progenitor diversity and neural cell

specification in the central nervous system. Frontiers in Cellular Neuroscience, v. 9, p. 1/358, 2015.

http://dx.doi.org/10.3389/fncel.2015.00358

16. SAMPAIO, L. S. ; TAVEIRA DA SILVA, R. ; LIMA, D. ; SAMPAIO, C. L. C. ; IANNOTTI, F. A. ; MAZZARELLA, E. ; DI MARZO,

V. ; VIEYRA, A ; REIS, R. A. M. ; EINICKER-LAMAS, M. . The endocannabinoid system in renal cells: regulation of Na+ transport by

CB1 receptors through distincts cell signalling pathways. British Journal of Pharmacology, v. 172, p. 4615-4625, 2015. DOI

10.1111/bph.13050

17. SCHACHTER, JULIETA ; VALCÁRCEL DELGADO, KELLY ; BARRETO-DE-SOUZA, VICTOR ; BOU-HABIB, DUMITH

CHEQUER ; PERSECHINI, PEDRO MUANIS ; MEYER-FERNANDES, JOSÉ ROBERTO . Inhibition of ecto-ATPase activities

impairs HIV-1 infection of macrophages. Immunobiology (Jena. 1979), v. 220, p. 589-596, 2015.

http://dx.doi.org/10.1016/j.imbio.2014.12.004

18. SCHITINE, CLARISSA ; NOGAROLI, LUCIANA ; COSTA, MARCOS R. ; HEDIN-PEREIRA, CECILIA . Astrocyte heterogeneity in

the brain: from development to disease. Frontiers in Cellular Neuroscience, v. 9, p. 76, 2015. http://dx.doi.org/10.3389/fncel.2015.00076

19. SILVA, ADRIANA F. ; ALVES, FLÁVIO L. ; PEDRON, CIBELE N. ; TORRES, MARCELO D.T. ; SILVA, LEANDRO S. ;

PINHEIRO, ANA A.S. ; MIRANDA, ANTONIO ; OLIVEIRA, VANI X. . Anti-plasmodial activity of Bradykinin and analogs.

Bioorganic & Medicinal Chemistry Letters (Print), v. 000, p. 000-000, 2015. http://dx.doi.org/10.1016/j.bmcl.2015.05.071

20. SILVA, ADRIANA F. ; TORRES, M. D. T. ; SILVA, L. S. ; ALVES, FLÁVIO L. ; Pinheiro, A. A. S. ; MIRANDA, ANTONIO ;

CAPURRO, M. L. ; OLIVEIRA, VANI X. . New linear antiplasmodial peptides related to angiotensin II. Malaria Journal (Online), v. 14,

p. 433-442, 2015.

21. SILVA-FILHO, J.L. ; SOUZA, M.C. ; HENRIQUES, M.G. ; MORROT, A. ; SAVINO, W. ; CARUSO-NEVES, C. ; PINHEIRO, A.A.S.

. Renin-angiotensin system contributes to naive T-cell migration in vivo. Archives of Biochemistry and Biophysics (Print), v. 000, p. 000-

000, 2015. http://dx.doi.org/10.1016/j.abb.2015.02.035

22. SOUZA, MARIANA C ; SILVA, JOHNATAS D ; PÁDUA, TATIANA A ; TORRES, NATÁLIA D ; ANTUNES, MARIANA A ;

XISTO, DEBORA G ; ABREU, THIAGO P ; CAPELOZZI, VERA L ; MORALES, MARCELO M ; PINHEIRO, ANA A ; CARUSO-

NEVES, CELSO ; HENRIQUES, MARIA G ; ROCCO, PATRICIA R M . Mesenchymal stromal cell therapy attenuated lung and kidney

injury but not brain damage in experimental cerebral malaria. Stem cell research & therapy, v. 6, p. 1-15, 2015.

http://dx.doi.org/10.1186/s13287-015-0093-2

23. TORRES, MARCELO DER TOROSSIAN ; SILVA, ADRIANA FARIAS ; DE SOUZA SILVA, LEANDRO ; DE SÁ PINHEIRO, ANA

ACÁCIA ; OLIVEIRA, VANI XAVIER JR. . Angiotensin II restricted analogs with biological activity in the erythrocytic cycle of

Plasmodium falciparum. Journal of Peptide Science (Print), v. 21, p. 24-28, 2015. http://dx.doi.org/10.1002/psc.2714

24. TRENTIN-SONODA, MAYRA; DA SILVA, ROGÉRIO CIRINO ; KMIT, FERNANDA VIEIRA ; ABRAHÃO, MARIANA VIEIRA ;

MONNERAT CAHLI, GUSTAVO ; BRASIL, GUILHERME VISCONDE ; MUZI-FILHO, HUMBERTO ; SILVA, PAULO ANDRÉ ;

TOVAR-MOLL, FERNANDA FREIRE ; VIEYRA, ADALBERTO ; MEDEI, EMILIANO* ; CARNEIRO-RAMOS, MARCELA

152


152

SORELLI . Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice. Plos

One, v. 10, p. e0139350, 2015. http://dx.doi.org/10.1371/journal.pone.0139350 *IN COLLABORATION WITH TOVAR-MOLL

(AL1) AND MEDEI (AL 16)


1. ABREU, THIAGO P. ; SILVA, LEANDRO S. ; TAKIYA, CHRISTINA M. ; SOUZA, MARIANA C. ; HENRIQUES, MARIA G. ;

PINHEIRO, ANA ACACIA S. ; CARUSO-NEVES, CELSO . Mice Rescued from Severe Malaria Are Protected against Renal Injury

during a Second Kidney Insult. Plos One, v. 9, p. e93634, 2014. http://dx.doi.org/10.1371/journal.pone.0093634

2. ALENCAR, ALLAN K.N. ; PEREIRA, SHARLENE L. ; DA SILVA, FLAVIA E. ; MENDES, LUIZA V.P. ; CUNHA, VALERIA DO

M.N. ; LIMA, LIDIA M. ; MONTAGNOLI, TADEU L. ; CARUSO-NEVES, CELSO ; FERRAZ, EMANUELLE B. ; TESCH,

ROBERTA ; NASCIMENTO, JOSÉ H.M. ; SANT?ANNA, CARLOS M.R. ; FRAGA, CARLOS A.M. ; BARREIRO, ELIEZER J. ;

SUDO, ROBERTO T. ; ZAPATA-SUDO, GISELE . N-acylhydrazone derivative ameliorates monocrotaline-induced pulmonary

hypertensionthrough the modulation of adenosine AA2R activity. International Journal of Cardiology (Print), v. 1, p. 1-9, 2014.

http://dx.doi.org/10.1016/j.ijcard.2014.02.022

3. ALVAREZ, CORA LILIA ; SCHACHTER, JULIETA ; DE SÁ PINHEIRO, ANA ACACIA ; SILVA, LEANDRO DE SOUZA ;

VERSTRAETEN, SANDRA VIVIANA ; PERSECHINI, PEDRO MUANIS ; SCHWARZBAUM, PABLO JULIO . Regulation of

Extracellular ATP in Human Erythrocytes Infected with Plasmodium falciparum. Plos One, v. 9, p. e96216, 2014.


4. ALVES-BEZERRA, M. ; COSENTINO-GOMES, DANIELA ; PAES LS ; ROCCO-MACHADO, N. ; GONDIM, K.C. ; MEYER-

FERNANDES, JOSÉ ROBERTO . Identification of uncoupling protein 4 from the blood-sucking insect Rhodnius prolixus and its

possible role on protection against oxidative stress. Insect Biochemistry and Molecular Biology, p. 24-33, 2014.


5. ARAÚJO, GEISSY L. L. ; ARAÚJO, JESSICA A. M. ; SCHROEDER, TIMM ; TORT, ADRIANO B. L. ; COSTA, MARCOS R. . Sonic

hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis. Frontiers in

Cellular Neuroscience, v. 8, p. 1/77-11, 2014. http://dx.doi.org/10.3389/fncel.2014.00077

6. ARAUJO, T. ; BORGES, J. ; RAMOS, C.* ; MEYER-FERNANDES, J. R. ; OLIVEIRA JUNIOR, R. ; PASCUTTI, P*. ; FOGUEL, D*.

; PALHANO, F. . Conformational Changes in Human Hsp70 Induced by High Hydrostatic Pressure Produce Oligomers with ATPase

Activity but without Chaperone Activity. Biochemistry (Easton), v. 53, p. 2884-2889, 2014. http://dx.doi.org/10.1021/bi500004q *IN

COLLABORATION WITH FOGUEL (AL 2), RAMOS (AL 7)

7. AZEVEDO-MARTINS, A. C. ; MACHADO, A. C. L. ; KLEIN, C. C. ; CIAPINA, L. ; GONZAGA, L. ; VASCONCELOS, A. T. R. ;

SAGOT, M. F. ; DE SOUZA, W*. ; EINICKER-LAMAS, M. ; GALINA, A. ; MOTTA, M. C. M. . Mitochondrial respiration and

genomic analysis provide insight into the influence of the symbiotic bacterium on host trypanosomatid oxygen consumption. Parasitology

(London. Print), v. 1, p. 1-11, 2014. http://dx.doi.org/10.1017/s0031182014001139 *IN COLLABORATION WITH DE SOUZA (AL

9)

8. BEIRAL, H. J. ; RODRIGUES-FERREIRA, C. ; FERNANDES, A. M. ; GONSALEZ, S. R. ; MORTARI, N. C. ; TAKIYA, C. M. ;

SORENSON*, M. M. ; FIGUEIREDO-FREITAS, C. ; GALINA, A. ; VIEYRA, A . The Impact of Stem Cells on Electron Fluxes, Proton

Translocation and ATP Synthesis in Kidney Mitochondria After Ischemia/Reperfusion. Cell Transplantation, v. 23, p. 207-220, 2014.

http://dx.doi.org/10.3727/096368912X659862 *IN COLLABORATION WITH SORENSON (AL 2)

9. BRUNO, STEFANIA ; COLLINO, FEDERICA ; IAVELLO, ALESSANDRA ; CAMUSSI, GIOVANNI . Effects of Mesenchymal

Stromal Cell-Derived Extracellular Vesicles on Tumor Growth. Frontiers in Immunology (Online), v. 5, p. 382, 2014.


10. CARDOSO, L. H. D. ; BRITTO-BORGES, T. ; VIEYRA, A ; LOWE, J. . ATP7B activity is stimulated by PKC- in porcine liver.

International Journal of Biochemistry & Cell Biology, v. 54, p. 60-67, 2014. http://dx.doi.org/10.1016/j.biocel.2014.06.019

11. COLLINO, FEDERICA; BRUNO, STEFANIA ; LINDOSO, RAFAEL SOARES ; CAMUSSI, GIOVANNI . miRNA Expression in

Mesenchymal Stem Cells. Current Pathobiology Reports, v. 2, p. 101, 2014. http://dx.doi.org/10.1007/s40139-014-0045-z

12. COSENTINO-GOMES, D. ; ROCCO-MACHADO, N. ; Meyer-Fernandes, José Roberto . Rhodnius prolixus: Modulation of antioxidant

defenses by Trypanosoma rangeli. Experimental Parasitology, v. 145, p. 118-124, 2014. http://dx.doi.org/10.1016/j.exppara.2014.08.002

13. DA COSTA, MILENE R. ; PIZZATTI, LUCIANA ; LINDOSO, RAFAEL S. ; SANT’ANNA, JULLIANA FERREIRA ; DUROCHER,

BARBARA ; ABDELHAY, ELIANA ; VIEYRA, ADALBERTO . Mechanisms of kidney repair by human mesenchymal stromal cells

after ischemia: A comprehensive view using label-free MS E. Proteomics (Weinheim. Print), v. 14, p. n/a-n/a, 2014.


14. DA SILVA, JAQUELINE SOARES ; PEREIRA, SHARLENE LOPES ; MAIA, RODOLFO DO COUTO ; LANDGRAF, SHARON

SCHILLING ; CARUSO-NEVES, CELSO ; KÜMMERLE, ARTHUR EUGEN ; FRAGA, CARLOS ALBERTO MANSSOUR ;

BARREIRO, ELIEZER JESUS ; SUDO, ROBERTO TAKASHI ; ZAPATA-SUDO, GISELE . N-acylhydrazone improves exercise

intolerance in rats submitted to myocardial infarction by the recovery of calcium homeostasis in skeletal muscle. Life Sciences (1973), v.

94, p. 30-36, 2014. http://dx.doi.org/10.1016/j.lfs.2013.11.012

15. DE BARROS PERUCHETTI, D. ; CHENG, J. ; CARUSO-NEVES, C. ; GUGGINO, W. B. . Mis-regulation of mTOR complexes

induced by albuminuria in proximal tubules. The Journal of Biological Chemistry (Print), v. 289, p. 16790-16801, 2014.


16. DIAS, J. ; FERRAO, F. M. ; AXELBAND, F. ; CARMONA, A. K. ; LARA, L. S. ; VIEYRA, A. . ANG-(3-4) inhibits renal Na+-ATPase

in hypertensive rats through a mechanism that involves dissociation of ANG II receptors, heterodimers, and PKA. American Journal of

Physiology. Renal Physiology, v. 306, p. F855-F863, 2014. http://dx.doi.org/10.1152/ajprenal.00488.2013

17. DICK, C. F. ; SANTOS, A. L. A. ; MEYER-FERNANDES, JOSÉ ROBERTO . Inorganic phosphate uptake in unicellular eukaryotes.

Biochimica et Biophysica Acta. G, General Subjects (Print), v. 1840, p. 2123-2127, 2014. http://dx.doi.org/10.1016/j.bbagen.2014.03.014

18. DUPNIK, K. M. ; BAIR, T. B. ; MAIA, A. O. ; AMORIM, F. M. ; COSTA, M. R. ; KEESEN, T. S. L. ; VALVERDE, J. G. ; QUEIROZ,

M. D. C. A. P. ; MEDEIROS, L. L. ; DE LUCENA, N. L. ; WILSON, M. E. ; NOBRE, M. L. ; JOHNSON, W. D. ; JERONIMO, S. M. B.

. Transcriptional changes that characterize the immune reactions of leprosy. The Journal of Infectious Diseases, v. 1, p. jiu612, 2014.

http://dx.doi.org/10.1093/infdis/jiu612

19. FERRÃO, F. M. ; LARA, L. S. ; LOWE, J. . Renin-angiotensin system in the kidney: What is new?. World Journal of Nephrology, v. 3, p.

64, 2014. http://dx.doi.org/10.5527/wjn.v3.i3.64

20. FIGLIUOLO, VANESSA RIBEIRO ; CHAVES, SUZANA PASSOS ; SANTORO, G. F. ; COUTINHO, C. ; MEYER-FERNANDES,

JOSÉ ROBERTO ; ROSSI-BERGMANN, BARTIRA ; COUTINHO-SILVA, ROBSON . Periodate-oxidized ATP modulates macrophage

functions during infection with Leishmania amazonensis. Cytometry. Part A, v. 85, p. 588-600, 2014.

http://dx.doi.org/10.1002/cyto.a.22449

21. FIGUEIRA, M. F. ; MONNERAT-CAHLI, G. ; MEDEI, E*. ; CARVALHO, A. B. ; MORALES, M. M. ; LAMAS, M. E. ; DA

FONSECA, R. N. ; SOUZA-MENEZES, J. . MicroRNAs: potential therapeutic targets in diabetic complications of the cardiovascular and

renal systems. Acta Physiologica (Print), v. 211, p. 491-500, 2014. http://dx.doi.org/10.1111/apha.12316 *IN COLLABORATION

WITH MEDEI (AL 16)

22. FREITAS-MESQUITA, A. L. ; SOUZA, A. L. F. ; MEYER-FERNANDES, JOSÉ R. . Leishmania amazonensis: Characterization of an

ecto-pyrophosphatase activity. Experimental Parasitology, v. 137, p. 8-13, 2014. http://dx.doi.org/10.1016/j.exppara.2013.11.008

23. FREITAS-MESQUITA, ANITA ; MEYER-FERNANDES, JOSÉ . Biochemical Properties and Possible Roles of Ectophosphatase

Activities in Fungi. International Journal of Molecular Sciences (Online), v. 15, p. 2289-2304, 2014.

http://dx.doi.org/10.3390/ijms15022289

24. FUSCO, MARIA ALICE ; WAJSENZON, INÊS JÚLIA RIBAS ; DE CARVALHO, SERGIO LUIZ ; DA SILVA, ROSILANE

TAVEIRA ; EINICKER-LAMAS, MARCELO ; CAVALCANTE, LENY A. ; ALLODI, SILVANA . Vascular endothelial growth factor-

153


153

like and its receptor in a crustacean optic ganglia: A role in neuronal differentiation?. Biochemical and Biophysical Research

Communications (Print), v. 447, p. 299-303, 2014. http://dx.doi.org/10.1016/j.bbrc.2014.03.137

25. GIAROLA, N. L. ; Silveira ST ; INACIO, J. D. F. ; VIEIRA, L. P. ; AMARAL, E. E. A. ; MEYER-FERNANDES, J. R. . Leishmania

amazonensis: Increase in ecto-ATPase activity and parasite burden of vinblastine-resistant protozoa. Experimental Parasitology, v. 146, p.

25-33, 2014. http://dx.doi.org/10.1016/j.exppara.2014.08.013

26. GIL-SANZ, C. ; LANDEIRA, B. ; RAMOS, C*. ; COSTA, M. R. ; MUELLER, U. . Proliferative Defects and Formation of a Double

Cortex in Mice Lacking Mltt4 and Cdh2 in the Dorsal Telencephalon. The Journal of Neuroscience, v. 34, p. 10475-10487, 2014.

http://dx.doi.org/10.1523/JNEUROSCI.1793-14.2014 *IN COLLABORATION WITH RAMOS (AL 7)

27. GOMES, ANNE CAROLINE CANDIDO ; SAMPAIO, LUZIA DA SILVA ; SILVA, PAULO ANDRÉ DA ; LAMAS, MARCELO

EINICKER ; SAKURAGUI, CASSIA MÔNICA ; BARRETO JUNIOR, CLEBER BOMFIM ; SIMAS, NAOMI KATO ; KUSTER,

RICARDO MACHADO . In vitro effect of isoschaftoside isolated from Syngonium podophyllum ON PIG KIDNEY Na + , K + -

ATPASE. Química Nova (Impresso), v. 37, p. 1606-1609, 2014. http://dx.doi.org/10.5935/0100-4042.20140257

28. GRANGE, CRISTINA ; COLLINO, FEDERICA ; TAPPARO, MARTA ; CAMUSSI, GIOVANNI . Oncogenic micro-RNAs and Renal

Cell Carcinoma. Frontiers in Oncology, v. 4, p. 49, 2014. http://dx.doi.org/10.3389/fonc.2014.00049

29. GUIMARAES-COSTA, A. B. ; SOUZA-VIEIRA, T. S. ; PALETTA-SILVA, R. ; FREITAS-MESQUITA, A. L. ; MEYER-

FERNANDES, J. R. ; SARAIVA, E. M. . 3' -Nucleotidase/nuclease activity allows Leishmania parasites to escape killing by neutrophil

extracellular traps.. Infection and Immunity (Print), v. 82, p. 1732-1734, 2014. http://dx.doi.org/10.1128/iai.01232-13

30. LANDGRAF, SHARON SCHILLING ; SILVA, LEANDRO SOUZA ; PERUCHETTI, DIOGO BARROS ; SIRTOLI, GABRIELA

MODENESI ; MORAES-SANTOS, FELIPE ; PORTELLA, VIVIANE GOMES ; SILVA-FILHO, JOÃO LUIZ ; PINHEIRO, CARLA

SILVA ; ABREU, THIAGO PEREIRA ; TAKIYA, CHRISTINA MAEDA ; BENJAMIN, CLAUDIA FARIAS ; PINHEIRO, ANA

ACACIA SÁ ; CANETTI, CLAUDIO ; CARUSO-NEVES, CELSO . 5-Lypoxygenase Products Are Involved in Renal Tubulointerstitial

Injury Induced by Albumin Overload in Proximal Tubules in Mice. Plos One, v. 9, p. e107549, 2014.


31. LEPLETIER, AILIN ; DE ALMEIDA, LILIANE ; SANTOS, LEONARDO ; DA SILVA SAMPAIO, LUZIA ; PAREDES, BRUNO ;

GONZÁLEZ, FLORENCIA BELÉN ; FREIRE-DE-LIMA, CÉLIO GERALDO ; BELOSCAR, JUAN ; BOTTASSO, OSCAR ;

EINICKER-LAMAS, MARCELO ; PÉREZ, ANA ROSA ; SAVINO, WILSON ; MORROT, ALEXANDRE . Early Double-Negative

Thymocyte Export in Trypanosoma cruzi Infection Is Restricted by Sphingosine Receptors and Associated with Human Chagas Disease.

PLoS Neglected Tropical Diseases (Online), v. 8, p. e3203, 2014. http://dx.doi.org/10.1371/journal.pntd.0003203

32. LINDOSO, RAFAEL SOARES ; COLLINO, FEDERICA ; BRUNO, STEFANIA ; ARAUJO, DAYANA DA SILVA DE ;

SANT?ANNA, JULLIANA ; TETTA, CIRO ; PROVERO, PAOLO ; QUESENBERRY, PETER J ; VIEYRA, ADALBERTO ;

EINICKER-LAMAS, MARCELO ; CAMUSSI, GIOVANNI . Extracellular vesicles released from mesenchymal stromal cells modulate

miRNA in renal tubular cells and inhibit ATP depletion injury. Stem Cells and Development, v. 23, p. 140326161007001-23: 1809?1819,

2014. http://dx.doi.org/10.1089/scd.2013.0618

33. MARIOTINI-MOURA, C. ; BASTOS, M. S. ; CASTRO, F. F. ; TRINDADE, M. L. ; VASCONCELLOS, R. S. ; NEVES-DO-VALLE,

M. A. A. ; MOREIRA, B. P. ; SANTOS, R. F. ; OLIVEIRA, C. M. ; CUNHA, L. C. S. ; SOUTO, X. M. ; BRESSAN, G. C. ; SILVA-

JUNIOR, A. ; BAQU, M. M. ; BAHIA, M. T. ; ALMEIDA, M. R. ; MEYER-FERNANDES, J. R. ; FIETTO, J. . Trypanosoma cruzi

Nucleoside Triphosphate Diphosphohydrolase 1 (TcNTPDase-1) biochemical characterization, immunolocalization and possible role in

host cell adhesion. Acta Tropica, v. 130, p. 140-147, 2014. http://dx.doi.org/10.1016/j.actatropica.2013.11.008

34. MONÇÃO-RIBEIRO, LEONARDO C. ; FAFFE, DÉBORA S. ; SANTANA, PATRÍCIA T. ; VIEIRA, FLÁVIA S. ; DA GRAÇA,

CAROLYNE LALUCHA A. L. ; MARQUES-DA-SILVA, CAMILA ; MACHADO, MARIANA N. ; CARUSO-NEVES, CELSO ; ZIN,

WALTER A. ; BOROJEVIC, RADOVAN ; TAKIYA, CHRISTINA M. ; COUTINHO-SILVA, ROBSON . P2X7 Receptor Modulates

Inflammatory and Functional Pulmonary Changes Induced by Silica. Plos One, v. 9, p. e110185, 2014.


35. NEVES, R. F. C. ; FERNANDES, A. C. ; MEYER-FERNANDES, JR ; SOUTO-PADRÓN, THAIS* . Trypanosoma cruzi-secreted

vesicles have acid and alkaline phosphatase activities capable of increasing parasite adhesion and infection. Parasitology Research (1987.

Print), v. 113, p. 2961-2972, 2014. http://dx.doi.org/10.1007/s00436-014-3958-x IN COLLABORATION WITH SOUTO-PADRÓN

(AL 11)

36. PEREIRA-NEVES A. ; ROSALES-ENCINA, J. L. ; MEYER-FERNANDES, J.R. ; BENCHIMOL, M.* . Tritrichomonas foetus:

Characterisation of ecto-phosphatase activities in the endoflagelar form and their possible participation on the parasite?s transformation

and cytotoxicity. Experimental Parasitology, v. 142, p. 67-82, 2014. http://dx.doi.org/10.1016/j.exppara.2014.04.007 *IN

COLLABORATION WITH BENCHIMOL (AL 12)

37. RIBEIRO, VALDILENE S. ; CABRAL, EDJAIR V. ; SILVA, ALEXSANDRA R. ; PEREIRA-JUNIOR, SILVIO F. ; LIMA, VERA L.

M. ; CARVALHO, VERA C. O. ; FILHO, LEUCIO D. V. ; PAIXÃO, ANA D. O. ; CASTRO-CHAVES, CARMEN . Perinatally

Imposed Essential Fatty Acid Deficiency Changes Renal Function of the Adult Rat. Food and Nutrition Sciences, v. 05, p. 1991-1999,

2014. http://dx.doi.org/10.4236/fns.2014.520210

38. SAMPAIO, L S ; TAVEIRA DA SILVA, R ; LIMA, D ; SAMPAIO, C L C ; IANNOTTI, F A ; MAZZARELLA, E ; DI MARZO, V ;

VIEYRA, A ; REIS, R A M ; EINICKER-LAMAS, M . The Endocannabinoid System in Renal Cell: Regulation of Na+ Transport by CB

1 Receptors Through Distinct Cell Signaling Pathways. British Journal of Pharmacology, v. 172, p. n/a-n/a, 2014.

http://dx.doi.org/10.1111/bph.13050

39. SILVA, P. A. ; MONNERAT-CAHLI, G. ; PEREIRA-ACACIO, A. ; LUZARDO, R. ; SAMPAIO, L. S. ; LUNA-LEITE, M. A. ; LARA,

L. S. ; EINICKER-LAMAS, M. ; PANIZZUTTI, R. ; MADEIRA, C. ; VIEIRA-FILHO, L. D. ; CASTRO-CHAVES, C. ; RIBEIRO, V. S.

; PAIXÃO, A. D. O. ; MEDEI, E*. ; VIEYRA, A . Mechanisms Involving Ang II and MAPK/ERK1/2 Signaling Pathways Underlie

Cardiac and Renal Alterations during Chronic Undernutrition. Plos One, v. 9, p. e100410, 2014.

http://dx.doi.org/10.1371/journal.pone.0100410 *IN COLLABORATION WITH MEDEI (AL 16)

40. SILVA, PAULO A. ; MUZI-FILHO, HUMBERTO ; PEREIRA-ACÁCIO, AMAURY ; DIAS, JULIANA ; MARTINS, JOÃO F.S. ;

LANDIM-VIEIRA, MAICON ; VERDOORN, KARINE S. ; LARA, LUCIENNE S. ; VIEIRA-FILHO, LEUCIO D. ; CABRAL,

EDJAIR V. ; PAIXÃO, ANA D.O. ; VIEYRA, ADALBERTO . Altered signaling pathways linked to Angiotensin II underpin the

upregulation of renal Na+-ATPase in chronically undernourished rats. Biochimica et Biophysica Acta. Molecular Basis of Disease, v.

1842, p. 2357-2366, 2014. http://dx.doi.org/10.1016/j.bbadis.2014.09.017

41. SILVA-FILHO, J. L. ; CARUSO-NEVES, C. ; PINHEIRO, A. A. S. . IL-4: an important cytokine in determining the fate of T cells.

Biophysical Reviews, v. 6, p. 111-118, 2014. http://dx.doi.org/10.1007/s12551-013-0133-z

42. SOUZA, A. L. F. ; FREITAS-MESQUITA, A. L. ; VIEIRA, L. P. ; MAJEROWICZ, D. ; YUNES, N. D. ; SOARES, L. C. A. ;

MIRANDA, K. ; GONDIM, K. C. ; MEYER-FERNANDES, JOSÉ ROBERTO . Identification and Characterization of an Ecto-

Pyrophosphatase Activity in Intact Epimastigotes of Trypanosoma rangeli. Plos One, v. 9, p. e106852, 2014.


43. TEIXEIRA, SHEILA MATARUNA ; BRAGA LEG ; CARPI RS ; CALAZA, KARIN DA COSTA ; ARAUJO, ELIZABETH GIESTAL

DE ; LEÃO-FERREIRA, L.R. . The (Na+/K+)-ATPase Activity in the Developing Rat Retina: The Role of Insulin-Like Growth Factor-I

(IGF-I). Cellular and Molecular Neurobiology, v. 00, p. 00, 2014. http://dx.doi.org/10.1007/s10571-014-0119-9

44. VIEIRA-FILHO, LEUCIO D. ; CABRAL, EDJAIR V. ; FARIAS, JULIANE S. ; SILVA, PAULO A. ; MUZI-FILHO, HUMBERTO ;

VIEYRA, ADALBERTO ; PAIXÃO, ANA D. O. . Renal molecular mechanisms underlying altered Na+ handling and genesis of

hypertension during adulthood in prenatally undernourished rats. British Journal of Nutrition, v. 111, p. 1932-1944, 2014.

http://dx.doi.org/10.1017/S0007114513004236


1. ALENCAR, A. K. N. ; PEREIRA, S. L. ; MONTAGNOLI, T. L. ; MAIA, R. C. ; KUMMERLE, A. E. ; LANDGRAF, S. S. ; CARUSO-

NEVES, C. ; FERRAZ, E. B. ; TESCH, R. ; NASCIMENTO, J. H. M. ; SANT?ANNA, C. M. R. ; FRAGA, C. A. M. ; BARREIRO, E. J.

154


154

; SUDO, R. T. ; ZAPATA-SUDO, G. . beneficial effects of a novel agonist of the adenosine A 2A receptor on monocrotaline-induced

pulmonary hypertension in rats. British Journal of Pharmacology, p. n/a-n/a, 2013. http://dx.doi.org/10.1111/bph.12193

2. BRUNO, STEFANIA ; COLLINO, FEDERICA ; DEREGIBUS, MARIA CHIARA ; GRANGE, CRISTINA ; TETTA, CIRO ;

CAMUSSI, GIOVANNI . Microvesicles Derived from Human Bone Marrow Mesenchymal Stem Cells Inhibit Tumor Growth. Stem Cells

and Development, v. 22, p. 758-771, 2013. http://dx.doi.org/10.1089/scd.2012.0304

3. BRUNO, STEFANIA ; COLLINO, FEDERICA ; TETTA, CIRO ; CAMUSSI, GIOVANNI . Advances in Biochemical

Engineering/Biotechnology. 149. ed. Springer Berlin Heidelberg, 2013. [BOOK]

4. BUSSOLATI, B. ; LAURITANO, C. ; MOGGIO, A. ; COLLINO, F. ; MAZZONE, M. ; CAMUSSI, G. . Renal CD133+/CD73+

Progenitors Produce Erythropoietin under Hypoxia and Prolyl Hydroxylase Inhibition. Journal of the American Society of Nephrology, v.

24, p. 1234-1241, 2013. http://dx.doi.org/10.1681/ASN.2012080772

5. CATTA-PRETA, C. M. ; NASCIMENTO, M. C. ; GARCIA, M. C. F. ; SARAIVA EM ; MOTTA, M. C. M. ; MEYER-FERNANDES,

JOSÉ ROBERTO . The presence of a symbiotic bacterium in Strigomonas culicis is related to differential ecto-phosphatase activity and

influences the mosquito-protozoa interaction. International Journal for Parasitology, p. 571-577, 2013.

http://dx.doi.org/10.1016/j.ijpara.2013.02.005

6. COLLINO, F.; BRUNO, S. ; CAMUSSI, G. . MicroRNAs in Medicine. 8. ed. , 2013. [BOOK]

7. CORDEIRO, A. ; SOUZA, L. L. ; EINICKER-LAMAS, M. ; PAZOS-MOURA, C. C. . NON-CLASSIC THYROID HORMONE

SIGNALLING INVOLVED IN HEPATIC LIPID METABOLISM. JOURNAL OF ENDOCRINOLOGY, V. 216, P. R47-R57, 2013.

HTTP://DX.DOI.ORG/10.1530/JOE-12-0542

8. COSENTINO-GOMES, DANIELA ; ROCCO-MACHADO, N. ; SANTI, L. ; BROETTO, L. ; VAINSTEIN, M. ; MEYER-

FERNANDES, JR ; SCHRANK, A. ; SILVA, W. B. . Inhibition of ecto-phosphatase activity in conidia reduces adhesion and virulence of

Metharhision anisopliase on the host insect Dysdercus peruvianus. Current Microbiology (Print), v. 66, p. 467-474, 2013.

http://dx.doi.org/10.1007/s00284-012-0296-z

9. COSTA, M. R. ; VERDOORN, K. S. ; LINDOSO, R. S. ; EINICKER-LAMAS, M. ; VIEIRA-BEIRAL, H. J. ; WESSELY, O. ;

VIEYRA, A . Resident Stem Cells in Kidney Tissue. In: Regina Coeli dos Santos Goldenberg; Antonio Carlos Campos de Carvalho.

(Org.). Resident Stem Cells and Regenerative Therapy. 1sted.Amsterdam: Academis Press (Elsevier), 2013, v. , p. 1-31. [BOOK

CHAPTER]

10. DICK, C.F. ; DOS-SANTOS, A.L.A. ; MAJEROWICZ, D. ; PAES, L.S. ; GIAROLA, N.L. ; GONDIM, K.C. ; VIEYRA, A. ; MEYER-

FERNANDES, J.R. . Inorganic phosphate uptake in Trypanosoma cruzi is coupled to K+ cycling and to active Na+ extrusion. Biochimica

et Biophysica Acta. G, General Subjects (Print), v. 1830, p. 4265-4273, 2013. http://dx.doi.org/10.1016/j.bbagen.2013.04.034

11. DOS SANTOS A. L. A ; DICK, C. F. ; SILVEIRA ST ; FONSECA DE SOUZA A. L. ; MEYER-FERNANDES, J. R. . Trypanosoma

rangeli: An alkaline ecto-phosphatase activity is involved with survival and growth of the parasite. Experimental Parasitology, p. 459-465,

2013. http://dx.doi.org/10.1016/j.exppara.2013.08.014

12. FERNANDES, A. C. ; SOARES, D. ; SARAIVA EM ; MEYER-FERNANDES, JOSÉ ROBERTO ; SOUTO-PADRON, T* . Different

secreted phosphatase activities in. FEMS Microbiology Letters, v. 340, p. 117-128, 2013. http://dx.doi.org/10.1111/1574-6968.12080 *IN

COLLABORATION WITH SOUTO-PADRÓN (AL 11)

13. GIAROLA, N. L. ; ALMEIDA-AMARAL, E. E. ; COLLOPY-JUNIOR, ITALLO ; FONSECA DE SOUZA A. L. ; MAJEROWICZ, D. ;

PAES LS ; GONDIM, K. C. ; MEYER-FERNANDES, JOSÉ ROBERTO . Trypanosoma cruzi: The effects of heat shock on ecto-ATPase

activity. Experimental Parasitology, v. 133, p. 434-441, 2013. http://dx.doi.org/10.1016/j.exppara.2012.12.014

14. GOMEZ, L. S. ; ZANCAN, P. ; MARCONDES, M. C. ; RAMOS-SANTOS, L. ; MEYER-FERNANDES, JOSÉ ROBERTO ; SOLA-

PENNA, M. ; SILVA, D. . Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-

kinase. Biochimie (Paris. Print), p. 1336-1343, 2013. http://dx.doi.org/10.1016/j.biochi.2013.02.013

15. GONDIM, K.C. ; PENNINGTON, J. E. ; MEYER-FERNANDES, J. R. ; ALVES-BEZERRA, M. ; WELLS, M. A. . EFFECT OF

STARVATION ON LIPOPHORIN DENSITY IN FIFTH INSTAR LARVAL. Archives of Insect Biochemistry and Physiology, v. 84, p.

145-156, 2013. http://dx.doi.org/10.1002/arch.21133

16. LEMOS, THIAGO ; VERDOORN, KARINE S. ; NOGAROLI, LUCIANA ; BRITTO-BORGES, THIAGO ; BONILHA, THAÍS A. ;

MORENO, PILAR A.M. ; SILVA, OSMAN FEITOSA ; TORTELOTE, GIOVANE G. ; EINICKER-LAMAS, MARCELO . Biphasic

regulation of type ii phosphatidylinositol-4 kinase by sphingosine: cross talk between glycero- and sphingolipids in the kidney.

BIOCHIMICA ET BIOPHYSICA ACTA. BIOMEMBRANES, V. 1838, P. 1003-1009, 2013.

HTTP://DX.DOI.ORG/10.1016/J.BBAMEM.2013.12.007

17. LERY, LETÍCIA M.S. ; GOULART, CAROLINA L. ; FIGUEIREDO, FELIPE R. ; VERDOORN, KARINE S. ; EINICKER-LAMAS,

MARCELO ; GOMES, FABIO M. ; MACHADO, EDNILDO A. ; BISCH, PAULO M. ; VON KRUGER, WANDA M.A. . A

comparative proteomic analysis of vibrio cholerae o1 wild-type cells versus a phob mutant showed that the phob/phor system is required

for full growth and rpos expression under inorganic phosphate abundance. JOURNAL OF PROTEOMICS (PRINT), V. 86, P. 1-15, 2013.

HTTP://DX.DOI.ORG/10.1016/J.JPROT.2013.04.038

18. LOWE, J. ; VIEYRA, ADALBERTO . Aída Hassón-Voloch, uma mulher à frente do seu tempo. In: Darcy Fontoura de Almeida;

Wanderley de Souza*. (Org.). Construtores do Instituto de Biofísica Carlos Chagas Filho. 1ed.Rio de Janeiro: Corbã Editora Artes

Gráficas, 2013, v. , p. 95-110. [BOOK CHAPTER] *IN COLLABORATION WITH DE SOUZA (AL 9)

19. MAJEROWICZ, D. ; CEZIMBRAA, M. P. ; ALVES-BEZERRA, M. ; ENTRINGER, PETTER F. ; ATELLA, G. C. ; SOLA-PENNA, M.

; MEYER-FERNANDES, JOSÉ ROBERTO ; GONDIM, KATIA C. . Rhodnius prolixus lipophorin: lipid composition and effect of high

temperature on physiological role. Archives of Insect Biochemistry and Physiology, v. 82, p. 129-140, 2013.

http://dx.doi.org/10.1002/arch.21080

20. MUZI-FILHO, H. ; BEZERRA, C. G. P. ; SOUZA, A. M. ; BOLDRINI, L. C. ; TAKIYA, C. M. ; OLIVEIRA, F. L. ; NESI, R. T. ;

VALENCA, S. S. ; EINICKER-LAMAS, M. ; VIEYRA, A ; LARA, L. S. ; CUNHA, V. M. N. . Undernutrition Affects Cell Survival,

Oxidative Stress, Ca2+ Handling and Signaling Pathways in Vas Deferens, Crippling Reproductive Capacity. Plos One, v. 8, p. e69682,

2013. http://dx.doi.org/10.1371/journal.pone.0069682

21. NARDY, A. F. F. R.ANA FLÁVIA F. R. NARDY ; SILVA FILHO, J. L. ; PEREZ, A. R. ; MEIS, J.JULIANA DE MEIS ; FARIAS-DE-

OLIVEIRA, D. A. ; PENHA, L. ; OLIVEIRA, I. A. ; DIAS, W. ; TODESCHINI, A. ; FREIRE-DE-LIMA, C. G. ; BELLIO, M. ;

CARUSO-NEVES, C. ; ANA ACACIA S. PINHEIRO ; TAKIYA, C. M. ; BOTTASSO, O. ; SAVINO, W. ; MORROT, A. . Trans-

sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes. Microbes and

Infection, v. 1, p. 1-5, 2013. http://dx.doi.org/10.1016/j.micinf.2013.02.003

22. NOGAROLI, LUCIANA ; COSTA, MARCOS R . Macroglial Cells: Development, Types/Functions and Role in Disease. In: Charanjit

Kaur and Ling Eng Ang. (Org.). Glial Cells: Embryonic Development, Types/Functions and Role in Disease. 1ed.New York: Nova

Science Publishers, 2013, v. 1, p. 1-20. [BOOK CHAPTER]

23. NUNES, MARISE PINHEIRO ; FORTES, BÁRBARA ; SILVA-FILHO, JOÃO LUIZ ; TERRA-GRANADO, EUGÊNIA ; SANTOS,

LEONARDO ; CONDE, LUCIANA ; DE ARAÚJO OLIVEIRA, ISADORA ; FREIRE-DE-LIMA, LEONARDO ; MARTINS, MARINA

VIEIRA ; PINHEIRO, ANA ACACIA SÁ ; TAKYIA, CHRISTINA MAEDA ; FREIRE-DE-LIMA, CÉLIO GERALDO ;

TODESCHINI, ADRIANE REGINA ; DOSREIS, GEORGE ALEXANDRE ; MORROT, ALEXANDRE . Inhibitory Effects of

Trypanosoma cruzi Sialoglycoproteins on CD4+ T Cells Are Associated with Increased Susceptibility to Infection. Plos One, v. 8, p.


24. OLIVEIRA, FABIANA S. T. ; VIEIRA-FILHO, LEUCIO D. ; CABRAL, EDJAIR V. ; SAMPAIO, LUZIA S. ; SILVA, PAULO A. ;

CARVALHO, VERA C. O. ; VIEYRA, ADALBERTO ; EINICKER-LAMAS, MARCELO ; LIMA, VERA L. M. ; PAIXÃO, ANA D.

O. . Reduced cholesterol levels in renal membranes of undernourished rats may account for urinary Na+ loss. European Journal of

Nutrition, v. 52, p. 1233-1242, 2013. http://dx.doi.org/10.1007/s00394-012-0434-1

25. ORTEGA, FELIPE ; BERNINGER, BENEDIKT ; COSTA, MARCOS R. . Imaging and Tracking Stem Cells. 1. ed. Humana Press, 2013.

[BOOK]

26. PAIXAO, A. D.; ALEXANDER, B. T. . How the Kidney Is Impacted by the Perinatal Maternal Environment to Develop Hypertension.

Biology of Reproduction, v. 89, p. 1-10, 2013. http://dx.doi.org/10.1095/biolreprod.113.111823

155


155

27. PALETTA-SILVA, RAFAEL ; ROCCO-MACHADO, N. ; MEYER-FERNANDES, J.R. . NADPH Oxidase Biology and the Regulation

of the Tyrosine Kinase receptor Signaling and Cancer Drug Cytotoxicity. International Journal of Molecular Sciences (Online), v. 14, p.

3683-3704, 2013. http://dx.doi.org/10.3390/ijms14023683

28. PORTELLA, VIVIANE G. ; SILVA-FILHO, JOÃO L. ; LANDGRAF, SHARON S. ; DE RICO, THAIS BALDEZ ; VIEIRA, MARIA

APARECIDA R. ; TAKIYA, CHRISTINA MAEDA ; SOUZA, MARIANA C. ; HENRIQUES, MARIA G. ; CANETTI, CLAUDIO ;

PINHEIRO, ANA ACACIA S. ; BENJAMIM, CLAUDIA F. ; CARUSO-NEVES, CELSO . Sepsis-Surviving Mice Are More Susceptible

to a Secondary Kidney Insult. Critical Care Medicine, v. 1, p. 1-12, 2013. http://dx.doi.org/10.1097/CCM.0b013e3182746696

29. RODRIGUEZ, J.B.R. ; MUZI-FILHO, H. ; VALVERDE, R.H.F. ; QUINTAS, L.E.M. ; NOEL, F. ; EINICKER-LAMAS, M. ; CUNHA,

V.M.N. . Rat vas deferens serca2 is modulated by ca2+/calmodulin protein kinase ii-mediated phosphorylation. BRAZILIAN JOURNAL

OF MEDICAL AND BIOLOGICAL RESEARCH, V. 46, P. 227-234, 2013. HTTP://DX.DOI.ORG/10.1590/1414-431X20122616

30. SEQUERRA, E. B. ; COSTA, M. R. ; MENEZES, J. R. L. ; HEDIN-PEREIRA, C. . Adult neural stem cells: plastic or restricted neuronal

fates?. Development (Cambridge), v. 140, p. 3303-3309, 2013. http://dx.doi.org/10.1242/dev.093096

31. SILVA-FILHO, JOÃO LUIZ ; SOUZA, MARIANA CONCEIÇÃO ; FERREIRA-DASILVA, CLAUDIO TEIXEIRA ; SILVA,

LEANDRO SOUZA ; COSTA, MARIA FERNANDA SOUZA ; PADUA, TATIANA ALMEIDA ; HENRIQUES, MARIA DAS

GRAÇAS ; MORROT, ALEXANDRE ; SAVINO, WILSON ; CARUSO-NEVES, CELSO ; PINHEIRO, ANA ACACIA SÁ .

Angiotensin II Is a New Component Involved in Splenic T Lymphocyte Responses during Plasmodium berghei ANKA Infection. Plos


32. SIRKO, SWETLANA ; BEHRENDT, GWENDOLYN ; JOHANSSON, PIA ANNETTE ; TRIPATHI, PRATIBHA ; Costa, Marcos ;

BEK, SARAH ; HEINRICH, CHRISTOPHE ; TIEDT, STEFFEN ; COLAK, DILEK ; DICHGANS, MARTIN ; FISCHER, ISABEL

REBEKKA ; PLESNILA, NIKOLAUS ; STAUFENBIEL, MATTHIAS ; HAASS, CHRISTIAN ; SNAPYAN, MARINA ;

SAGHATELYAN, ARMEN ; TSAI, LI-HUEI ; FISCHER, ANDRÉ ; GROBE, KAY ; DIMOU, LEDA ; Götz, Magdalena . Reactive Glia

in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog Glia. Cell Stem Cell (Print), v. 12, p. 426-439, 2013.

http://dx.doi.org/10.1016/j.stem.2013.01.019

33. WENGERT, M. ; RIBEIRO, M.C. ; ABREU, T.P. ; COUTINHO-SILVA, R. ; LEÃO-FERREIRA, L.R. ; PINHEIRO, A.A.S. ;

CARUSO-NEVES, C. . Protein kinase C-mediated ATP stimulation of Na+-ATPase activity in LLC-PK1 cells involves a P2Y2 and/or

P2Y4 receptor. Archives of Biochemistry and Biophysics (Print), v. 1, p. 1-142, 2013. http://dx.doi.org/10.1016/j.abb.2013.03.013

156


156

AL 18 - Associated Laboratory of Immunology

- Coodinator:

Julio Scharfstein- IBCCF/UFRJ

- Researchers from national institutions: Ana Carolina Siqueira Couto de Oliveira- IBCCFº/UFRJ

Antonio Campos de Carvalho/IBCCF-UFRJ

Carla Eponina de Carvalho Pinto/UFF-RJ

Claudia Benjamin- IBCCF/UFRJ

Joseli Lannes Vieira Imunologista Fiocruz-RJ

Luiz Juliano Bioquímico/UNIFESP-São Paulo

Nils Erik Svensjö- IBCCF/UFRJ

Robson Coutinho/ IBCCF-UFRJ

Luciana Arruda, IMPPG/UFRJ

Patrícia Alvarenga/IBqMed-LDM


Herbert Tanowitz Patologista Albert Einstein/ EUA Doença de Chagas

Jörg Köhl- Imunologista Lübeck University/ Alemanha

José Marcos Ribeiro/NIH

Pierre Sirois- Farmacologista, Sherbrooke University /Canada


Clarissa Rodrigues Nascimento

(IBCCF/UFRJ);

Daniele Andrade (IBCCF/UFRJ);

Isabela Resende Pereira (IBCCF/UFRJ).


Erivan Schnaider Ramos Junior (completed

in 2014, BCCF/UFRJ);

Larissa Nogueira de Almeida (completed in

2015, IBCCF/UFRJ);

Lucas Vellasco de Mattos (IBCCF/UFRJ);


Rafaela Rangel Serra-IBCCF/UFRJ

(completed in 2015 - BCCF/UFRJ);

- Master's students (continuing list):

Julia Barbalho da Mota (IBCCF/UFRJ);

Eric Aguiar (IBCCF/UFRJ);

Matheus Ferreira da Silva Palazzo

(IBCCF/UFRJ).

- Technicians:

Alda Maria Fidelis Alves (IBCCF/UFRJ);

Carla Silva Fernandes (Service supplier

waived in 2016 by lack of funds -

IBCCF/UFRJ); Daniela de Oliveira Faustin

(Service supplier - IBCCF/UFRJ);

Leila da Conceição Faustino de Oliveira

Dutra (Service supplier - IBCCF/UFRJ).

157


157

In the past years, we have systematically

investigated the role of the endothelial

barrier in the pathogenesis of Chagas

disease.

During infection, innate sentinel cells sense

the presence of pathogens and send alert

signals that open the endothelial “flood

gates”, leading to the rapid diffusion of

plasma proteins through the infected

tissues. Dynamically regulated in order to

preserve tissue homeostasis, the endothelial

barrier of microvessels is further

destabilized by bradykinin (BK), a short-

lived proinflammatory peptide released

from high molecular weight kininogen by

plasma kallikrein. As the inflammatory

wave propagates, pathogens and immune

cells are jointly exposed to an unstable

microenvironment in which the levels of

reactive oxygen species are abruptly

elevated.

Using several models of T. cruzi infection,

we have recently demonstrated that

activation of perivascular mast cells drives

the activation of the “contact coagulation

system”, a web-like proteolytic network

that reversibly connect innate immunity to

inflammation and coagulation /

thrombogenesis.

Intravital microscopy in the hamster cheek

pouch combined to studies in transgenic

mice revealed that bradykinin (BK)-

induced proteolytic cascades propagate the

inflammatory wave evoked by this

flagellated protozoan. Although T. cruzi

destabilizes the endothelial barrier by

stimulating chemokine secretion via

activation of innate receptors (TLR2), we

verified that mast cell degranulation

promotes the diffusion of plasma-borne

contact factors (FXII and plasma kallikrein)

through peripheral sites of infection.

Further downstream, the exposure of FXII

(zymogen) to negatively charged polymers

(heparin and/or Polyphosphates) released

from mast cell granules culminates with

massive release of BK by plasma kallikrein.

Strikingly, we demonstrated that the

parasites take advantage of the elevated

levels of BK (and endothelin) released in

the inflamed heart to infect cardiovascular

cells through the activation of their cognate

GPCRs.

Using LPS-treated HCP to simulate

inflamed microvascular beds, we found that

TCTs triggered a prolonged edema via

activation of B1R, the inducible subtype of

kinin receptor. Assisted by high-resolution

echocardiography, we next inoculated

TCTs (Dm28c strain) intracardiacally in

mice and observed that T. cruzi DNA

(qPCR; 3 d p.i.) was markedly reduced in

the heart of MC-deficient mice, in WT mice

pretreated with cromoglycate (MC

stabilizer) or pretreated with infestin-4, a

specific inhibitor of Factor XIIa. Similarly,

intracardiac edema (2 h p.i.) and heart

parasitism (3 d p.i.) were inhibited in mice

pretreated with (i) subtype-specific

antagonists of BK receptors (B2R versus

B1R) or (ii) bosentan, a non-selective

antagonist of endothelin receptors

(ETAR/ETBR). Notably, severity of

myocarditis and heart fibrosis (30 d p.i.)

was redundantly attenuated in mice

pretreated with each one of the GPCR

blockers. Studies in WT and B1R-/- mice

infected systemically (Dm28c strain)

revealed that intracardiac parasitism (acute

phase; 14 d p.i.) and chronic

myocarditis/heart fibrosis (90 d p.i.) were

mitigated in the absence of B1R. Consistent

with these results, we found out that R-954,

a specific antagonist of B1R (applied daily

from 15-60 d p.i.), reduced the intracardiac

load of parasites in C57BL/6 mice acutely

infected by the myotropic Colombian

strain.

Therefore, we could demonstrate from

those results that pharmacological targeting,

such as B1R antagonists, stabilizes the

endothelial barrier, reducing intracardiac

parasitism and limiting the pathogenic

outcome (myocarditis/fibrosis) of Chagas

heart disease (Figure 1).

158


158

Figure 1: Endothelial barrier breakdown via the mast cell / Kallikrein-Kinin (MC/KKS) pathway fuels

intracardiac parasitism: working hypothesis. Left/top, TCTs liberated from ruptured pseudocysts induce a

subtle plasma leakage via synergism between tGPI (TLR2 ligand – innate immunity) and cruzipain (kinin-

releasing cysteine protease). Activation of endothelial B2R amplifies plasma leakage and subsequent formation

of kinins. Right side, generation of C5a anaphylatoxin and/or ET-1 (whose secretion is upregulated by

parasitized heart cells) activate cardiac MCs via C5aR and ETAR, respectively, leading to the release of

histamine and heparin/PolyP (contact activators) stored in MC granules. Acting on endothelium H1R,

histamine induces the extravasation of plasma proteins –including the contact phase zymogens (FXII, PK) into

parasite-laden tissues. Exposure of FXII/PK to MC-derived contact activators (heparin/PolyP) generates PKa,

the kininogenase that releases BK from HK. Iterative cycles of BK-induced endothelium (B2R) activation,

plasma leakage and MC degranulation propagate the edema spatially and temporally, generating increasing

levels of infection-promoting peptides (BK, DABK, ET-1) in peripheral tissues. Further downstream, the

trypomastigotes may potentiate their infectivity by co-opting the agonistic function of kinins and ET-1. This

mechanism may either involve (i) direct stimulation of endocytic uptake of the pathogen via interdependent

signaling of B2R, B1R and ETAR/ETBR or (ii) generation of ROS, which in turn induce plasma membrane

lesions whose repair require sealing via the [Ca2+]i-/ceramide endocytic pathway. Left/bottom, during the

course of chronic infection, TNF-α secreted by anti-parasite effector CD8+ T cells may induce endothelial

barrier breakdown, enabling diffusion of prooxidative ET-1 and C5 to peripheral tissues, leading to the

activation of the MC/KKS pathway further downstream. DABK (the B1R agonist) originates from kininase I-

dependent metabolism of BK. Sustained edema may occur due to TNF-α-driven upregulation of B1R in the

endothelial lining.

159


159

This research resulted in a manuscript,

which has already been submitted and is in

the latest revision for publication in the

journal Plos Pathogens. It is important to

emphasize that a collaboration with AL 16

(headed by Professor Antonio Carlos

Campos de Carvalho) provided us with the

expertise required to inoculate T. cruzi

directly into the mouse heart, using

facilities installed at CENABIO / INBEB.

Future perspectives: Using the hamster cheek pouch model, we

have obtained evidences that tissue

parasitism promotes neovascularization via

mast cell (MC) dependent activation of the

Kallikrein-Kinin (KKS). Ongoing studies

may clarify whether T. cruzi-induced

angiogenesis (MC/KKS pathway) is

orchestrated by activation of innate

receptors for other intracelular pathogens

(see below).

Studies in the hamster cheek pouch infected

by Dengue and Zika are planned, pending

on funding. We wish to determine whether

these viruses replicate in the cheek pouch

and characterize the microvascular,

vascular and/or neurological lesions

eventually associated to infection - the

focus (from a mechanistic perspective)

being directed at the

proinflammatory/proangiogenic MC/KKS

pathway.

The initiative to use the hamster cheek

pouch as a model for Zika/Dengue infection

is legitimated by published studies

emphasizing that the Syrian hamster is a

murine host that faithfully reproduces the

symptoms of humans infected by Ebola and

hanta viruses.

Funding from INBEB is critically required

to support our new work plan: in the long

run, it should be possible to target the

MC/KKS pathway using siRNA,

adenovirus recombinant vectors and the

CRIPS/CAS9 system, all of which recently

implemented by American and Chinese

groups.

160


160

AL 18 main publications in 2016: 1. ANDRADE, DANIELE DOS SANTOS; NASCIMENTO, CLARISSA R.; OLIVEIRA, ANA CAROLINA; BRASIL,

GUILHERME*; CARVALHO-PINTO, CARLA EPONINA; RAMOS-JUNIOR, ERIVAN SCHNAIDER; SERRA,

RAFAELA RANGEL; DA MOTA, JULIA BARBALHO; ALMEIDA, LARISSA N.; VELLASCO, LUCAS; FORTES, FABIO; ANDRADE, MARCUS V.; PEREIRA, ISABELA RESENDE; LANNES-VIEIRA, JOSELI; SOEIRO, MARIA

DE NAZARÉ; JULIANO, LUIZ; SIROIS, PIERRE; ALVARENGA, PATRÍCIA HESSAB; SICURO, FERNANDO

LENCASTRE; CAMPOS-DE-CARVALHO, ANTÔNIO C.*; SVENSJÖ, ERIK; SCHARFSTEIN, JULIO. Inflammatory Edema Propagated Via the Kallikrein-Kinin System Fuels Intracardiac Parasitism and Worsens Heart

Pathology in Experimental Chagas Disease. PLoS Pathogens (Submitted). *IN COLLABORATION WITH AL 16

(CAMPOS-DE-CARVALHO AND BRASIL).

2. SCHARFSTEIN J. KININS. In: Encyclopedia of Inflammatory Diseases, M. Parnham (ed.), Springer Basel 2016; DOI

10.1007/978-3-0348-0620-6_127-2 (in press) [CHAPTER BOOK]

3. RODRIGUES M ; BARBIRATO D ; LUIZ R ; SCHARFSTEIN, J. ; SALLES G ; FERES-FILHO E . Effect of Anti-hypertensive Therapy with Angiotensin Converting Enzyme Inhibitors on Chronic Periodontitis: a Case-Control Study.

Oral Diseases, 2016.

AL 18 main publications in 2015: 1. RAMOS-JUNIOR, E. S. ; MORANDINI, A. C. ; ALMEIDA-DA-SILVA, C. L. C. ; FRANCO, E. J. ; Potempa, J. ;

NGUYEN, K. A. ; OLIVEIRA, A. C. ; ZAMBONI, D. S. ; OJCIUS, D. M. ; SCHARFSTEIN, J. ; COUTINHO-SILVA,

R. . A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection. Journal of Dental Research, v. 94, p. 1233-1242, 2015. http://dx.doi.org/10.1177/0022034515593465

AL 18 main publications in 2014: 1. MORANDINI AC, RAMOS JUNIOR ES, POTEMPA J, KY-ANH N, OLIVEIRA ACSC , BELLIO M, OJCIUS DM,

SCHARFSTEIN J, COUTINHO, RS. Porphyromonas gingivalis Fimbriae Dampen P2X7-Dependent Interleukin-1beta

Secretion. Journal of Innate Immunity, v. 1662, p. 1-15, 2014. doi:10.1159/000363338

2. SCHMITZ V, ALMEIDA LN, SVENSJÖ E, MONTEIRO AC, KÖHL J, SCHARFSTEIN J. C5a and bradykinin receptor cross-talk regulates innate and adaptive immunity in Trypanosoma cruzi infection. J Immunol. 193(7):3613-

23,2014. doi: 10.4049/jimmunol.1302417.

3. SVENSJÖ E, ALMEIDA LN, VELLASCO, JULIANO L, SCHARFSTEIN J. Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-

Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B 2 and B

1 Receptors. Mediators of Inflammation (Print),p. 1-12, 2014. doi: 10.1155/2014/143450.

AL 18 main publications in 2013: 1. ALVARENGA PH, XU X, OLIVEIRA F, CHAGAS AC, NASCIMENTO CR, FRANCISCHETTI IMB, JULIANO

MA, JULIANO L , SCHARFSTEIN J, VALENZUELA JG, RIBEIRO JMC, ANDERSEN J F. Novel Family of Insect

Salivary Inhibitors Blocks Contact Pathway Activation by Binding to Polyphosphate, Heparin, and Dextran Sulfate. Arteriosclerosis, Thrombosis, and Vascular Biology, v. 33, p. 2759-70, 2013. doi: 10.1161/ATVBAHA.113.302482

2. SCHARFSTEIN J, ANDRADE DS, SVENSJÖ E, OLIVEIRA AC, NASCIMENTO CR . The kallikrein-kinin system in

experimental Chagas disease: a paradigm to investigate the impact of inflammatory edema on GPCR-mediated pathways of host cell invasion by Trypanosoma cruzi. Frontiers in Immunology, v. 3, p. 1-20, 2013. doi:

10.3389/fimmu.2012.00396

161


161

AL 19 - Associated Laboratory of Cellular and Molecular

Neurology

- Coordinator:

Rosália Mendez Otero - Instituto de Biofísica Carlos Chagas Filho (IBCCF/UFRJ)

- Researchers from national institutions: Arthur Giraldi Guimarães - Uenf

Bianca Gutfilen – FM/UFRJ

Gabriel Rodriguez Freitas - UFF

Guilherme Ferreira da Motta Rezende – HU/UFRJ

Joaquim Fernando Mendes da Silva – IQ/UFRJ

Lea Mirian Fonseca – FM/UFRJ

Marcelo Felippe Santiago – IBCCF/UFRJ

Rogério Panizzutti – ICB/UFRJ


Tatiane Duarte Cozendey – UFRJ

Louise Alessandra Mesentier Louro – UFRJ

Pablo Domizi – UFRJ

Maria Fernanda Toledo - UFRJ


Teresa Puig Pijuan (UFRJ)

Tanira Giara Mello (UFRJ)


Fernando Breno de Oliveira Ribeiro – UFRJ;

Rafael Ferreira Monteiro Soares – UFRJ.

The main lines of research in our group aim

to establish animal models of neurological

diseases which will allow us to test the

safety and efficacy of therapy with stem

cells, steps necessary for clinical studies

with stem cells in neurological patient. The

isolation and characterization of the stem

cells to be used in the therapies is also an

important component of our research. It is

also important to be able to label the cells in

order to investigate the migration and

homing of these cells after transplantation

into the animal models and patients. In this

respect, we have investigated labeling

techniques which could be used both in pre-

clinical and clinical studies. During the four

years’ period covered by this report (2013

to 2016) we were able to conclude some of

the goals of our proposal and the main

results of each specific objective will be

summarized below:

Model of amyotrophic lateral sclerosis:

Amyotrophic lateral sclerosis (ALS) is a

progressive neurological disease that

selectively affects the motor neurons. The

details of the mechanisms of selective

motor-neuron death remain unknown and

no effective therapy has been developed.

We investigated the therapy with bone-

marrow mononuclear cells (BMMC) in a

mouse model of ALS (SOD1G93A mice).

We observed a mild transitory delay in the

disease progression in the animals injected

with BMMC in the presymptomatic phase.

However, we observed no increase in the

lifespan. When we injected BMMC in the

symptomatic phase, we observed no

difference in the animals’ lifespan or in the

disease progression. Immunohistochemistry

for NeuN showed a decrease in the number

of motor neurons during the course of the

disease, and this decrease was not affected

by either treatment. Using different

162


162

strategies to track the BMMC, we noted

that few cells remained in the spinal cord

after transplantation. This observation could

explain why the BMMC therapy had only a

transitory effect. This is the first report of

intraspinal BMMC therapy in a mouse

model of ALS (Gubert, et. al., Stem Cell

Research & Therapy, 2016).

Model of transient global ischemia:

Global cerebral ischemia (GCI) results in

death of the pyramidal neurons in the CA1

layer of the hippocampus. we used the four-

vessel occlusion (4VO) model of GCI to

investigate a potential neuroprotective role

of bone-marrow mononuclear cells

(BMMCs) transplantation. BMMCs (3×107)

were injected through the carotid artery, 1

or 3 days after ischemia (DAI), and the

number of cells undergoing degeneration

was investigated in brains at 7 DAI. A

significant decrease in the number of dying

cells was observed in the treated group,

compared to animals treated with saline.

Biodistribution of the injected cells (1 or 3

DAI) was investigated by 99mTechnetium

labeling of the BMMCs and subsequent

image analysis 2 h after transplantation

(Figure 1). BMMCs treatment significantly

reduced the number of FJ-C positive cells

in the hippocampal CA1 layer at 7 DAI. We

also observed a decrease in the number of

activated microglia/macrophage (ED1-

positive cells) in the BMMCs-treated group

compared with the untreated group. Our

data show that BMMCs are able to

modulate the microglial response and

reduce neurodegeneration in the CA1 layer

(Bernardo-Ramos, et. al., Braisn Research,

2013).

Figure 1: Biodistribution and homing of BMMCs. Representative coronal and sagittal SPECT/CT images of a

control animal (A, B) and of ischemic animals injected 1 DAI (C,D) and injected 3 DAI (E, F) indicating

uptake of 99mTc-BMMCs in the injection site; coronal SPECT/CT image demonstrating uptake in the liver of

an ischemic animal injected 3 DAI (G); transversal image showing uptake in the spleen of an ischemic animal

injected 3 DAI (H).

163


163

Model of optic nerve injury:

In adult mammals, the regeneration

of the optic nerve is very limited and at the

moment there are several groups trying

different approaches to increase retinal

ganglion cell (RGC) survival and axonal

outgrowth. One promising approach is cell

therapy. We performed intravitreal

transplantation of bone-marrow

mononuclear cells (BMMCs) after optic

nerve crush in adult rats and we

demonstrated an increase in RGC survival

and axon outgrowth 14 days after injury.

We also investigated if these results could

be sustained for a longer period of time. In

an attempt to prolong RGC survival, we

established a new protocol with two

BMMC injections, the second one 7 days

after the injury. Untreated animals received

two injections of saline. We observed that

although the axonal outgrowth was still

increased after the second BMMC

injection, the RGC survival was not

significantly different from untreated

animals (Figure 2). These results

demonstrate that BMMCs transplantation

promotes neuroregeneration at least until 28

days after injury (Zaverucha-do-Valle,

et.al., Brain Research, 2014).

Figure 2: A second BMMC injection does not

prolong the persistence of the transplanted cells in

the host eye. Detection of FeraTrack-labeled

BMMCs by in vivo MRI. In the Figure, we can see

representative images of coronal, horizontal and

sagittal (ipsilateral to the injury) planes at

different survival times. Arrows indicate

hypointense (black) spots corresponding to

FeraTrack-labeled cells in the vitreous body of the

left eye.

Still in a model of optic nerve

injury, we also investigated the therapeutic

potential of mesenchymal stem cells (MSC)

injected into the vitreous body. In

summary, MSC protected RGC and

stimulated axon regeneration after optic

nerve crush (Figure 3). The long period

when the transplanted cells remained in the

eye may account for the effect observed

(Mesentier-Louro, et. al., PlosOne, 2014).

Figure 3. Detection of FeraTrack-labeled MSCs

by in vivo MRI. MSC were labeled with Fera

Track for 4 h and injected in the vitreous body of

the left eye after optic nerve crush. (A-L)

Representative images of in vivo MRI at coronal

(A,E,I), horizontal (B,F,J), and sagittal planes

(C,G,K; at left eye level and D,H,L; at right eye

level) at different survival times. Arrows indicate

hypointense (black) spots corresponding to

FeraTrack-labeled cells in the vitreous body of the

left eye. Labeled cells were found at 2 (A-C), 14

(E-G) and 18 weeks (I-K) after optic nerve crush

and cell transplantation. The right eye was

injected with the washing solution of the cells; no

signal was detected (D,H,L and right hemisphere

of coronal and horizontal images). The lenses are

circled with dashed lines; right (R) and left (L)

hemispheres.

Clinical trials:

BM-MNC transplantation improves

recovery in experimental models of

ischemic stroke. Clinical trials are ongoing

to test efficacy in stroke patients. We

performed a nonrandomized, open-label

Phase I clinical trial to assess the

biodistribution of bone marrow

mononuclear cells (BM-MNC) delivered by

different routes in patients with subacute

middle cerebral artery ischemic stroke.

Twelve patients were included, between 19

and 89 days after stroke, and received 1–5

× 108 BM-MNCs. After bone marrow

harvesting, BM-MNCs were labeled with

technetium-99m and intra-arterially or

intravenously delivered together with the

unlabeled cells. BM-MNCs were

successfully injected without complications

in all patients. No significant hemodynamic

or clinical changes occurred during the

http://www.sciencedirect.com/science/journal/00068993

164


164

injection. The intra-arterial group had

greater radioactive counts in the liver and

spleen and lower counts in the lungs at 2

and 24 h, while in the brain they were low

and similar for both routes (Figure 4). BM-

MNC labeling with technetium-99m

allowed imaging for up to 24 h after intra-

arterial or intravenous injection in stroke

patients (Rosado-de-Castro, et. al.,

Regenerative Medicine, 2013).

Figure 4. Whole-body scintigraphies in anterior

view of a patient. Whole-body scintigraph at (A) 2

h and (B) 24 h after cell transplantation.

Increasing uptake is indicated by color shift from

blue to red to yellow to white.

We also performed a pooling data analysis

of two pilot clinical trials with autologous

BM-MNCs transplantation in ischemic

stroke patients. Cell dose and route were

analyzed to evaluate their relation to good

outcome (m-Rankin scale [mRS] score 0–2)

at 6 months. Similar to preclinical studies, a

higher dose of autologous BM-MNC was

related to better outcome in stroke patients,

especially when more than 310 × 106 cells

are injected (Moniche, et. al., Stem Cell

International, 2016).

Induced pluripotent stem cells as a

model to study Zika Virus:

Lately, we have engaged into studies about

Zika Virus (ZIKV), a mosquito-borne

Flavivirus first identified in rhesus

monkeys in the Zika Forest in Uganda in

1947, and only being reported infecting

humans in 1952. After the outbreak of

ZIKV in Brazil in 2015, a 20-fold increase

in the number of microcephaly cases was

observed, establishing a temporal

association. The Pan American Health

Organization and the World Health

Organization issued an epidemiological

alert regarding ZIKV infection, congenital

malformations and neurological

syndromes. Studies in animal models have

also reinforced the link between ZIKV

infection and congenital malformations.

These, however, do not reproduce

properly the human infection, since mice

are resistant to ZIKV infection, relying on

either type I interferon defective strains,

direct injection on fetal cerebral ventricles

or injection into the bloodstream of

immunocompetent female pregnant mice

at extraordinary high titers. To investigate

the deleterious effects of ZIKV infection,

we used human neural progenitor cells

(NPC), derived from induced pluripotent

stem cells (iPSC). We found that NPC are

highly susceptible to ZIKV and the

infection results in cell death. ZIKV

infection led to a marked reduction in cell

proliferation, ultrastructural alterations

and induction of autophagy. Induction of

apoptosis of Sox2+ cells was demonstrated

by activation of caspases 3/7, 8 and 9, and

by ultrastructural (Figure 5) and flow

cytometry analyses. ZIKV-induced death

of Sox2+ cells was prevented by

incubation with the pan-caspase inhibitor,

Z-VAD-FMK. By confocal microscopy

analysis we found an increased number of

cells with supernumerary centrosomes.

Live imaging showed a significant

increase in mitosis abnormalities,

including multipolar spindle, chromosome

laggards, micronuclei and death of

progeny after cell division. FISH analysis

for chromosomes 12 and 17 showed

increased frequency of aneuploidy, such

as monosomy, trisomy and polyploidy.

Our study reinforces the link between

ZIKV and abnormalities in the developing

human brain, including microcephaly

(Souza, et. al., Scientific Reports, 2016).

165


165

Figure 5: Ultrastructural analysis of NPC cultures after ZIKV infection. (A,B) Transmission electron

micrographs of mock-infected cells, showing nuclei and organelles with normal aspect after 24 and 72 h of

culture. (C–F) ZIKV-infected cells 24 (C,D), 48 (E) and 72 (F) h after infection. Cells in early (C) and late (F)

apoptotic processes. (D) The presence of large perinuclear autophagic vacuoles (AV) can be observed. Black

arrows indicate mitochondria with altered morphology. (E)


1. GUBERT, FERNANDA ; DECOTELLI, ANA B. ; BONACOSSA-PEREIRA, IGOR ; FIGUEIREDO, FERNANDA R. ; ZAVERUCHA-DO-VALLE, CAMILA ; TOVAR-MOLL, FERNANDA* ; HOFFMANN, LUÍSA ; URMENYI,

TURAN P. ; SANTIAGO, MARCELO F. ; MENDEZ-OTERO, ROSALIA . Intraspinal bone-marrow cell therapy at

pre- and symptomatic phases in a mouse model of amyotrophic lateral sclerosis. Stem cell research & therapy, v. 7, p. 45, 2016. http://dx.doi.org/10.1186/s13287-016-0293-4 *IN COLLABORATION WITH AL 1 (TOVAR-MOLL).

2. JASMIN ; SOUZA G T ; LOUZADA NETO, R. A. ; ROSADO-DE-CASTRO PH ; MENDEZ-OTERO, R. ; CAMPOS

DE CARVALHO, ANTONIO C* . Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations. International Journal of Nanomedicine (Online), 2016. *IN COLLABORATION WITH AL 16

(CAMPOS-DE-CARVALHO)

3. JASMIN, JASMIN ; PETERS, V. M. ; SPRAY, D. C. ; MENDEZ-OTERO, R. . Effect of mesenchymal stem cells and mouse embryonic fibroblasts on the development of preimplantation mouse embryos. In Vitro Cellular & Developmental

Biology. Animal (Online), v. 2016, p. January 2016, 2016. http://dx.doi.org/10.1007/s11626-015-9997-5

4. JOLKKONEN, JUKKA ; MENDEZ-OTERO, ROSALIA ; DE FREITAS, GABRIEL RODRIGUEZ ; BOLTZE, JOHANNES ; ROSADO-DE-CASTRO, PAULO HENRIQUE . The Current State of Cell Therapies for Cerebrovascular

Diseases. Stem Cells International, v. 2016, p. 1-2, 2016. http://dx.doi.org/10.1155/2016/5215824

5. MESENTIER-LOURO, L. A. ; NICOLO, S. ; ROSSO, P. ; VITIS, L. ; CASTOLDI V ; LEOCANI L ; MENDEZ-OTERO, R. ; SANTIAGO, M. F. ; TIRASSA P ; RAMA P ; LAMBIASE A . Time-dependent nerve growth factor

signaling changes in the rat retina during optic nerve crush-induced degeneration of retinal ganglion cells. International

Journal of Molecular Sciences (Online), v. 18, p. 98-115, 2016. http://dx.doi.org/10.3390/ijms18010098 6. MESENTIER-LOURO, LOUISE A. ; MENDEZ-OTERO, R. . Comment on retinal ganglion cell electrical activity,

mTOR signaling > and optic nerve regeneration. Journal of Eye Science, v. 1, p. 1, 2016.

7. MESENTIER-LOURO, LOUISE A. ; ZAVERUCHA-DO-VALLE, CAMILA ; ROSADO-DE-CASTRO, PAULO H. ; SILVA-JUNIOR, ALMIR J. ; PIMENTEL-COELHO, PEDRO M. ; MENDEZ-OTERO, ROSALIA ; SANTIAGO,

MARCELO F. . Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases. Stem Cells

International, v. 2016, p. 1-16, 2016. http://dx.doi.org/10.1155/2016/5078619 8. MONICHE, FRANCISCO ; ROSADO-DE-CASTRO, PAULO HENRIQUE ; ESCUDERO, IRENE ; ZAPATA,

ELENA ; DE LA TORRE LAVIANA, FRANCISCO JAVIER ; MENDEZ-OTERO, ROSALIA ; CARMONA,

MAGDALENA ; PIÑERO, PILAR ; BUSTAMANTE, ALEJANDRO ; LEBRATO, LUCÍA ; CABEZAS, JUAN ANTONIO ; GONZALEZ, ALEJANDRO ; DE FREITAS, GRABRIEL R. ; MONTANER, JOAN . Increasing Dose of

Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled

Analysis of Two Clinical Trials. Stem Cells International, v. 2016, p. 1-8, 2016. http://dx.doi.org/10.1155/2016/8657173 9. PIMENTEL-COELHO, P. M. ; ROSADO-DE-CASTRO PH ; MENDEZ-OTERO, R. . Editorial: New Insights into the

Pathophysiology and Treatment of Neonatal Hypoxic-ischemic Encephalopathy. Frontiers in neurology, v. 7, p. 192,

2016.

166


166

10. ROSADO-DE-CASTRO, PAULO HENRIQUE ; DE CARVALHO, FELIPE GONÇALVES ; DE FREITAS, GABRIEL

RODRIGUEZ ; MENDEZ-OTERO, ROSALIA ; PIMENTEL-COELHO, PEDRO MORENO . Review of Preclinical

and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage. Stem Cells International, v.

2016, p. 1-18, 2016. http://dx.doi.org/10.1155/2016/4617983

11. SOUZA, B. S. F. ; SAMPAIO, G. L. A. ; PEREIRA, C. S. ; CAMPOS, G. S. ; SARDI, S. I. ; FREITAS, L. A. R. ; FIGUEIRA, C. P. ; PAREDES, B. D. ; NONAKA, C. K. V. ; AZEVEDO, C. M. ; ROCHA, V. P. C. ; ANTONIO C.

BANDEIRA, ; MENDEZ-OTERO, R. ; SANTOS, R. R. ; SOARES, M. B. P. . Zika virus infection induces mitosis

abnormalities and apoptotic cell death of human neural progenitor cells. Scientific Reports, v. 6, p. srep39775, 2016. http://dx.doi.org/10.1038/srep39775


1. CARRIER-RUIZ, A.; EVARISTO-MENDONÇA F; MENDEZ-OTERO, R. ; V, R. ; RIBEIRO-RESENDE VT .

Biological behavior of mesenchymal stem cells on poly-caprolactone filaments and a strategy for tissue engineering of segments of the peripheral nerves. Stem cell research & therapy, v. 6, p. 128, 2015. doi: 10.1186/s13287-015-0121-2.


2. AZEVEDO-PEREIRA, R. L. ; LIMA, A. M. ; MACHADO, G. S. ; PAREDES, B. ; RODRIGUES, D. ; CARVALHO,

A. C. C. ; MENDEZ-OTERO, R. . Expression of ganglioside 9-O-acetyl GD3 in undifferentiated embryonic cells. Cell Biology International, v. 100, p. 100, 2014. http://dx.doi.org/10.1002/cbin.10335

3. JASMIN, ; JELICKS, LINDA A ; TANOWITZ, H. ; PETERS, V. M. ; MENDEZ-OTERO, R. ; CAMPOS DE

CARVALHO A. C.* ; Spray, David C. . Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Microbes and Infection, p. S1286, 2014.

http://dx.doi.org/10.1016/j.micinf.2014.08.016 *IN COLLABORATION WITH AL 16 (CAMPOS-DE-

CARVALHO)

4. MESENTIER-LOURO, LOUISE ALESSANDRA ; ZAVERUCHA-DO-VALLE, CAMILA ; DA SILVA-JUNIOR,

ALMIR JORDÃO ; NASCIMENTO-DOS-SANTOS, GABRIEL ; GUBERT, FERNANDA ; DE FIGUEIRÊDO, ANA

BEATRIZ PADILHA ; TORRES, ANA LUIZA ; PAREDES, BRUNO D. ; TEIXEIRA, CAMILA ; TOVAR-MOLL,

FERNANDA* ; MENDEZ-OTERO, ROSALIA ; SANTIAGO, MARCELO F. . Distribution of Mesenchymal Stem

Cells and Effects on Neuronal Survival and Axon Regeneration after Optic Nerve Crush and Cell Therapy. Plos One, v.

9, p. e110722, 2014. http://dx.doi.org/10.1371/journal.pone.0110722 *IN COLLABORATION WITH AL 1 (TOVAR-

MOLL). 5. ROSADO-DE-CASTRO, PAULO H. ; PIMENTEL-COELHO, P. M. ; GUTFILLEN, B. ; SOUZA, S. A. L. ; DE

FREITAS G. R. ; MENDEZ-OTERO, R. ; FONSECA, L. M. B. . Radiopharmaceutical stem cell tracking for neurological diseases. BioMed Research International, v. 2014, p. 1, 2014. http://dx.doi.org/10.1155/2014/417091

6. ZAVERUCHA-DO-VALLE, CAMILA ; MESENTIER-LOURO, L.A. ; GUBERT, FERNANDA ; MORTARI, N. ;

PADILHA, A. B. ; PAREDES, B. ; MENCALHA, ANDRE LUIZ ; ABDELHAY, ELIANA ; TEIXEIRA, C. ;

FERREIRA, F. G. ; TOVAR-MOLL, F.* ; SOUZA, S. A. ; MENDEZ-OTERO, R. ; MENDEZ-OTERO, R. ;

SANTIAGO, M. F. . Sustained effect of bone marrow mononuclear cell therapy in axonal regeneration in a model of

optic nerve crush. Brain Research, p. S0006, 2014. http://dx.doi.org/10.1016/j.brainres.2014.08.070 *IN

COLLABORATION WITH AL 1 (TOVAR-MOLL).


1. BERNARDO RAMOS, ALANE ; VASCONCELOS-DOS-SANTOS, ANDRÉIA ; DE SOUZA, SERGIO AUGUSTO

LOPES ; ROSADO-DE-CASTRO, PAULO HENRIQUE ; DA FONSECA, LEA MIRIAN BARBOSA ; GUTFILEN, BIANCA ; MONTEIRO CINTRA, WAGNER ; MENDEZ-OTERO, ROSALIA . Bone-Marrow Mononuclear Cells

Reduce Neurodegeneration In Hippocampal Ca1 Layer After Transient Global Ischemia In Rats. Brain Research, v. 13,

p. 01, 2013. http://dx.doi.org/10.1016/j.brainres.2013.05.024 2. CASTRO P H R ; PIMENTEL-COELHO, P. M. ; BARBOSA DA FONSECA, L. M. ; DE FREITAS G. R. ; MENDEZ-

OTERO, R. . The rise of cell therapy trials for stroke: review of published and registered studies. Stem Cells and

Development, v. 22, p. 130319071515000, 2013. http://dx.doi.org/10.1089/scd.2013.0089 3. DE FREITAS G. R. ; MENDEZ-OTERO, R. . Intra-arterial cell therapy in stroke patients. Cell-Based Therapies in

Stroke. 1ed.New York: Springer, 2013, v. , p. 181-190. [BOOK CHAPTER]

4. MENDEZ-OTERO, R.; PIMENTEL-COELHO, P. M. ; UKRAINTSEV, S. ; MCJARROW, P. . Role of gangliosides in neurological development and the influence of dietary sources. In: Ronald Ross Watson, George Grimble, Victor R.

Preedy, Sherma Zibadi. (Org.). Nutrition in Infancy. 1ed.New York: Totowa, NJ, 2013, v. 2, p. 105-118. [BOOK

CHAPTER] 5. ROSADO-DE-CASTRO, PAULO H. ; SCHMIDT, F. R. ; BATTISTELLA, V. ; SOUZA, S. A. L. ; GUTFILLEN, B. ;

GOLDENBERG R C ; KASAI-BRUNSWICK, T. H. ; GASPARETTO, EMERSON LEANDRO ; SILVA, R. M. ;

WAJNBERG E ; BRASIL, P. E. A. A. ; GASPARETTO, E. ; MAIOLINO, A. ; ALVES-LEON, S. V. ; ANDRE, C. ; MENDEZ-OTERO, R. ; DE FREITAS G. R. ; FONSECA, L. M. B. . Biodistribution of bone marrow mononuclear cells

after intra-arterial or intravenous transplantation in subacute stroke patients. Regenerative Medicine (Print), v. 8, p. 145-

155, 2013. http://dx.doi.org/10.2217/rme.13.2

167


167

AL 20 - Associated Laboratory of Inflammation and

Metabolism

- Coordinator:

Fernando Augusto Bozza - Instituto de Pesquisa Clínica Evandro Chagas/IPEC-FOC

- Researchers from national institutions: Alysson Roncally Carvalho – IBCCF/UFRJ

Antonio Giannella Neto – PEB/UFRJ

Hugo C. Castro Faria Neto - Fiocruz/RJ

Marcus F. Oliveira – IBqM/UFRJ

Rosana Souza Rodrigues – ID’OR/HUCFF-

UFRJ

Walter Araújo Zin - IBCCF/UFRJ


Alessandro Gaviraghi - UFRJ

Camila Baptista – Fiocruz

Cassiano Fellipe Gonçalves – Fiocruz

Joana da Costa Pinto D'avila – Fiocruz

Mariana Nascimento Machado - UFRJ

Monica Farah Pereira – Fiocruz

Patricia Alves Reis – Fiocruz


Alcendino Candido Jardim Neto (UFRJ)

Ana Paula Miranda Mendonça (UFRJ)

Andre Costa Ferreira (Fiocruz)

Carolina Araujo Moraes (Fiocruz)

Caroline Mendes Ferreira (UFRJ)

Ermesom Mesquita (Fiocruz)

Felipe Gomes Pinheiro (UFRJ)

Flávia Muniz de Mesquita (UFRJ)

Gabriel Casulari da Motta Ribeiro (UFRJ)

Grazielle Viana Ramos (Fiocruz)

Helena D'Anunciação (Fiocruz)

Isaclaudia Gomes de Azeedo (Fiocruz)

Leandro Andrade Chinalia (UFRJ)

Leonardo Bugarin de Andrade Neumamm

(UFRJ)

- Doctoral students (Continued listing):

Luis Felipe Santos da Cruz Paula (UFRJ)

Marcelo Vieira Leão Nunes (UFRJ)

Niedja Silva Carvalho (UFRJ)

Pedro Kurtz (Fiocruz)

Pedro Mendes de Azambuja Rodrigues

(Fiocruz)

Priscila da Penha Apolinário Barboza

(UFRJ)

Ricardo Gaudio de Almeida (UFRJ)

Samuel D. Moscavitch (Fiocruz)

Wollner Marteko (UFRJ)


Aline Reis da Sila (Fiocruz)

Alvaro Antonio Cardoso Bastos (UFRJ)

Beatriz Esteves Nogueira (UFRJ)

Clara Santanna Melo de Oliveira (UFRJ)

Emílio Teles (Fiocruz)

Liz Maria Queiroz Machado (UFRJ)

Luciana Camara Belem (UFRJ)

Maiara Lima (Fiocruz)

Raissa Lapa (UFRJ)

Rodrigo Cavalcante dos Santos (UFRJ)

Tathyane Igreja da Silva (Fiocruz)


Daiane Chaves Amorim (UVA)

Rodiesley dos Santos Rosa (UFRJ)

Thamyres Alves da Silva (UFRJ)

Tailane dos Santos Almeida (UFRJ)

Alexia Nascimento Cardozo (UFRJ)

Igor Marcondes de Andrade (UFRJ)

The main research areas in our group deal

with applications of biomedical imaging in

different problems and fields of research,

with special focus into metabolism

repercussions of a given inflammatory

process. We summarized below some of the

main results obtained during the four years’


2016):

Dengue

Worldwide, dengue is the most prevalent

human arbovirus disease. Dengue infection

may cause a range of clinical

manifestations from self-limiting febrile

illness through to a life-threatening

syndrome accompanied by both bleeding

and shock. Thrombocytopenia is frequently

observed in mild and severe disease;

however, the mechanisms involved in

DENV-induced platelet activation and

thrombocytopenia are incompletely

understood. Our results demonstrate that

platelets from patients with dengue present

signs of activation, mitochondrial

168


168

dysfunction and activation of the apoptosis

caspase cascade, which may contribute to

the development of thrombocytopenia in

patients with dengue. Our results also

suggest the involvement of DC-SIGN as a

critical receptor in DENV-dependent

platelet activation (Hottz et. al., Journal of

Thrombosis and Haemostasis, 2013).

We observed increased levels of platelet–

monocyte aggregates in blood samples from

patients with dengue, especially patients

with thrombocytopenia and increased

vascular permeability. Moreover, the

exposure of monocytes from healthy

volunteers to platelets from patients with

dengue induced the secretion of the

cytokines IL-1β, IL-8, IL-10 and MCP-1,

whereas exposure to platelets from healthy

volunteers only induced the secretion of

MCP-1. In addition to the well-established

modulation of monocyte cytokine responses

by activated platelets through P-selectin

binding, we found that interaction of

monocytes with apoptotic platelets mediate

IL-10 secretion through phosphatidylserine

recognition in platelet–monocyte

aggregates. Moreover, IL-10 secretion

required platelet–monocyte contact but not

phagocytosis. Together, our results

demonstrate that activated and apoptotic

platelets aggregate with monocytes during

dengue infection and signal specific

cytokine responses that may contribute to

the pathogenesis of dengue (Hottz et. al., J.

Immunol., 2014).

We also demonstrated that DV infection

leads to assembly of nucleotide-binding

domain leucine rich repeat containing

protein (NLRP3) inflammasomes,

activation of caspase-1, and caspase-1–

dependent IL-1β secretion (Figure 1). Our

findings also indicate that platelet-derived

IL-1β is chiefly released in microparticles

through mechanisms dependent on

mitochondrial reactive oxygen species–

triggered NLRP3 inflammasomes.

Inflammasome activation and platelet

shedding of IL-1β–rich microparticles

correlated with signs of increased vascular

permeability. Moreover, microparticles

from DV-stimulated platelets induced

enhanced permeability in vitro in an IL-1–

dependent manner. Our findings provide

new evidence that platelets contribute to

increased vascular permeability in DV

infection by inflammasome-dependent

release of IL-1β. (Hottz, et. al., Blood,

2013)

Figure 1: Platelets obtained from healthy subjects and patients with dengue were stained with anti-NLRP3

(green) and anti-ASC (red) and examined by confocal microscopy using an Olympus FV10i-O with a 240×

lens. The images were processed using FLUOVIEW FV1000 MPE software version 5.0 and further analyzed

using Adobe Photoshop CS Version 8.0. Bars represent 10 µm.

169


169

To evaluate lung changes associated with

dengue infection, we retrospectively

analyzed 2,020 confirmed cases of dengue.

Twenty-nine of these patients (11 females

and 18 males aged 16–90 years) underwent

chest computed tomography (CT), which

yielded abnormal findings in 17 patients: 16

patients had pleural effusion (the sole

finding in six patients) and 11 patients had

pulmonary abnormalities. Lung

parenchyma involvement ranged from

subtle to moderate unilateral and bilateral

abnormalities. The most common finding

was ground-glass opacity in eight patients,

followed by consolidation in six patients.

CT findings of lower respiratory tract

involvement were uncommon. When

abnormalities were present, pleural effusion

was the most frequent finding and lung

involvement was often mild or moderate

and bilateral (Figure 2). Extensive lung

abnormalities are infrequent even in severe

disease and when present should lead

physicians to consider other diagnostic

possibilities (Rodriques, et. al., PlosOne,

2014).

Figure 2. A 16-year-old girl with a confirmed

diagnosis of dengue and reduced exercise

tolerance and breathlessness. CT images show

large bilateral pleural effusion (a, mediastinal

window) and no abnormality of the lung

parenchyma other than compressive atelectasis (b,

lung window).

Sepsis

Sepsis is a major cause of mortality and

morbidity in intensive care units. Current

evidence indicates that dysregulation of the

host inflammatory response to infectious

agents is central to the mortality of patients

with sepsis. Strategies to block

inflammatory mediators such as PAF have

been investigated as adjuvant therapies for

sepsis. PAF-AH, the enzyme responsible

for PAF degradation, showed positive

results in pre-clinical studies and phase II

clinical trials, but the results of a phase III

study were disappointing. we investigated

the potential protective mechanism of PAF-

AH in sepsis using the murine model of

cecal ligation and puncture (CLP). We

concluded that administration of exogenous

rPAF-AH reduced inflammatory injury,

altered cytokine levels and favored bacterial

clearance with a clear impact on mortality

through modulation of MCP-1/CCL2 and

NO levels in a clinically relevant sepsis

model (Teixeira-da-Cunha, et al., PlosOne,

2013).

Sepsis- associated encephalopathy (SAE) is

an early and common feature of severe

infections. Oxidative stress is one of the

mechanisms associated with the

pathophysiology of SAE. The goal of this

study was to investigate the involvement of

NADPH oxidase in neuroinflammation and

in the long-term cognitive impairment of

sepsis survivors. Acute oxidative damage to

the hippocampus was identified by

increased 4-HNE expression in parallel

with an increase in Nox2 gene expression

after sepsis. Pharmacological inhibition of

Nox2 with apocynin completely inhibited

hippocampal oxidative stress in septic

animals (Figure 3). Pharmacologic

inhibition or the absence of Nox2 in

gp91phox-/- mice prevented glial cell

activation, one of the central mechanisms

associated with SAE. Finally, treatment

with apocynin and inhibition of

hippocampal oxidative stress in the acute

phase of sepsis prevented the development

of long-term cognitive impairment. Our

results demonstrate that Nox2 is the main

source of reactive oxygen species (ROS)

involved in the oxidative damage to the

hippocampus in SAE and that Nox2-

derived ROS are determining factors for

cognitive impairments after sepsis. These

findings highlight the importance of Nox2-

derived ROS as a central mechanism in the

development of neuroinflammation

associated with SAE (Hernandes, et. al., J.

of Neuroinflammation, 2014).

170


170

Figure 3: Apocynin treatment prevents oxidative stress and astrogliosis in the hippocampus early after sepsis.

(A) WT mice were treated with apocynin one hour after sepsis onset. Brain oxidative stress was measured six

hours after sepsis onset. Values are ratios of 4-HNE/cyclophilin B (a low molecular weight loading control)

densitometry, expressed as mean ± SEM (n = 4 each group). The bottom figure shows two representative bands

of Sham, Sham + Apo, Sepsis and Sepsis + Apo. The statistical significance is expressed as: *P < 0.05 and

***P < 0.001. (B) Representative digital images of Iba-1 immunoreactivity (in green) in the CA1 region

indicate that apocynin treatment did not affect microglia activation. (C) Representative digital images of

GFAP (in green) immunoreactivity in CA1 region indicate thickening of astrocyte processes, especially around

blood vessels; apocynin treatment decreased astrogliosis after sepsis. Nuclear 4',6-diamidino-2-phenylindole

(DAPI) staining is shown in blue. Images are representative of three independent experiments (n = 6 per

experimental group). Apo: apocynin. Scale bar: 20μm.

Mechanical ventilation

When alveoli collapse the traction forces

exerted on their walls by adjacent expanded

units may increase and concentrate. These

forces may promote its re-expansion at the

expense of potentially injurious stresses at

the interface between the collapsed and the

expanded units. We developed an

experimental model to test the hypothesis

that a local non-lobar atelectasis can act as

a stress concentrator, contributing to

inflammation and structural alveolar injury

in the surrounding healthy lung tissue

during mechanical ventilation. The

microCT images of the animals revealed

that the volume of the atelectasis was 0.12

and 0.21 cm3, respectively (Figure 4). The

microCT images demonstrated that there

was not any other lung collapse at the start

of the protocol. There were more alveolar

disruption and neutrophilic infiltration in

the peri-atelectasis region than the

corresponding contralateral lung (control)

in both groups. Edema was higher in the

peri-atelectasis region than the


in the VT20/ZEEP than VT10/PEEP3

group. The volume-to-surface ratio was

higher in the peri-atelectasis region than the


in both groups. Our findings suggest that a

local non-lobar atelectasis acts as a stress

concentrator, generating structural alveolar

injury and inflammation in the surrounding

lung tissue (Retamal et. al., Critical Care,

2014).

Figure 4: Micro computed tomography

(MicroCT) images. MicroCT images over time of

one representative animal of tidal volume = 20

ml/kg and positive end-expiratory pressure = 0

cmH2O group are exhibited. The black arrow

indicates the atelectasis and the blocker.

171


171

Evidence exists that during pressure support

ventilation (PSV), the addition of an

extrinsic (ie, ventilator-generated) breath-

to-breath variability (BBV) of breathing

pattern improves respiratory function. If

BBV is beneficial per se, choosing the PS

level that maximizes it could be considered

a valid strategy for conventional PSV. In

this study, we evaluated the effect of

different PS levels on intrinsic BBV in

acutely ill, mechanically ventilated subjects

to determine whether a significant

relationship exists between PS level and

BBV magnitude. Despite a significant

increase in spontaneous activity with PS

reduction, BBV was not influenced by the

PS level and was as low as 30% for all

evaluated parameters (Cruz, et. al.,

Respiratory Care, 2014).

Silicosis

Silicosis is a lung disease caused by

inhaling crystalline silica, which induces a

fibrogenic reaction in the tissue, and

represents the most common

pneumoconiosis. Silicosis is a preventable

but incurable disease that can be fatal

owing to significant health impairment. CT,

especially high-resolution CT (HRCT), has

been considered the best test for assessing

environmental and occupational respiratory

diseases. In addition, image processing

through lung volume quantification using

MDCT (Q-MDCT) has the potential

advantage of estimating regional volumes

in different compartments that are already

determined by classifications previously

proposed in the literature. The forced

oscillation technique (FOT) is a simple

method to investigate the mechanical

properties of the respiratory system and

represents the current state-of-the-art in the

assessment of lung function. We performed

a cross-sectional study comprised 36 non-

smoker patients with silicosis and 20

matched control subjects who were

submitted to FOT and multidetector CT

(MDCT). Compared with the control

subjects, the MDCT evaluation

demonstrated that patients with silicosis

exhibited greater total lung mass. These

patients also had larger non-aerated and

poorly aerated compartments, which

included nodules and scarring. Compared

with the control subjects, FOT evaluation

demonstrated that patients with silicosis

exhibited changes in both reactive and

resistive properties of the respiratory

system. In these patients, there was a

greater heterogeneity of the respiratory

system and increased work of breathing.

Significant correlations between non-

aerated compartment size and FOT

parameters that reflect the non-

homogeneity of the respiratory system were

observed. The dynamic compliance of the

respiratory system was negatively

correlated with non-aerated compartment

size, while the impedance at 4 Hz was

positively correlated with non-aerated

compartment size. Patients with silicosis

have heavier lungs. In these patients, a

larger non-aerated compartment is

associated with a worsening of lung

function. A more significant pulmonary

involvement is associated with a loss of

homogeneity and increased mechanical

load of the respiratory system (Figure 5)

(Lopes et. al., British J. of Radiology,

2015).

Figure 5. Three-dimensional (3D) images of the

lungs reconstructed from the binary matrix of the

region of interest in the anteroposterior view (top

left). The 3D representation (posteroanterior view)

of the lung parenchyma and each compartment

reveals the hyperaerated compartment (red), the

poorly aerated compartment (light grey), the non-

aerated compartment (black) and the normally

aerated compartment (blue).

A new 3D image method for microglial

morphology analysis

Microglial cells are tissue-resident

macrophages of the central nervous system.

They are extremely dynamic, sensitive to

their microenvironment and present a

characteristic complex and heterogeneous

morphology and distribution within the

brain tissue. Many experimental clues

highlight a strong link between their

172


172

morphology and their function in response

to aggression. However, due to their

complex “dendritic-like” aspect that

constitutes the major pool of murine

microglial cells and their dense network,

precise and powerful morphological studies

are not easy to realize and complicate

correlation with molecular or clinical

parameters. Using the knock-in mouse

model CX3CR1GFP/+, we developed a 3D

automated confocal tissue imaging system

coupled with morphological modelling of

many thousands of microglial cells

revealing precise and quantitative

assessment of major cell features: cell

density, cell body area, cytoplasm area and

number of primary, secondary and tertiary

processes. We determined two

morphological criteria that are the

complexity index (CI) and the covered

environment area (CEA) allowing an

innovative approach lying in (i) an accurate

and objective study of morphological

changes in healthy or pathological

condition, (ii) an in situ mapping of the

microglial distribution in different

neuroanatomical regions and (iii) a study of

the clustering of numerous cells, allowing

us to discriminate different sub-populations.

Our results on more than 20,000 cells by

condition confirm at baseline a regional

heterogeneity of the microglial distribution

and phenotype that persists after induction

of neuroinflammation by systemic injection

of lipopolysaccharide (LPS). Using

clustering analysis, we highlight that, at

resting state, microglial cells are distributed

in four microglial sub-populations defined

by their CI and CEA with a regional pattern

and a specific behaviour after challenge

(Figure 6). Our results counteract the

classical view of a homogenous regional

resting state of the microglial cells within

the brain. Microglial cells are distributed in

different defined sub-populations that

present specific behaviour after

pathological challenge, allowing

postulating for a cellular and functional

specialization. Moreover, this new

experimental approach will provide a

support not only to neuropathological

diagnosis but also to study microglial

function in various disease models while

reducing the number of animals needed to

approach the international ethical

statements (Verdonk, et. al., J. of

Neuroinflammation, 2016).

Fig. 6: The characterization of microglial cells by

morphological criteria. A) Confocal images,

representing a sub-part of the analysed image in

the frontal cortex region after maximum intensity

projection. The individual microglia based on

GFP fluorescence appears in white outline. The

scale bar equals 50 μm. B) Ramification detection

based on GFP fluorescence with AcapellaTM

software. The segmented ramifications linked to

an individual microglia are shown artificially in

green, the unattributed ramifications in white.

The scale bar equals 50 μm. C) The morphological

criteria to characterize a microglial cell. The cell

body detection (blue) and cytoplasm area (pink)

have performed as a starting point to characterize

a microglial cell. The complexity index (green) and

the covered environment area (CEA in orange)

have been deduced from ramification detection.

The scale bar equals 10 μm. D) Two-dimensional

cartography at a single cell resolution. Colours

correspond to the range of complexity and CEA

with a gradient from a low level of complexity and

CEA (yellow) to a high level of complexity and

CEA (red). The scale bar equals 50 μm. For

illustration, the images are contrast adjusted to

aid in visualizing the GFP expression

173


173


1. ABREU, MARIANA DE ; NETO, ALCENDINO CÂNDIDO ; CARVALHO, GIOVANNA ; CASQUILLO, NATALIA

VASCONCELOS ; CARVALHO, NIEDJA ; OKURO, RENATA ; RIBEIRO, GABRIEL C.MOTTA. ; MACHADO, MARIANA ;

CARDOZO, ALÉXIA ; SILVA, ALINE SANTOS E ; BARBOZA, THIAGO ; VASCONCELLOS, LUIZ RICARDO ; RODRIGUES,

DANIELLE ARAUJO ; CAMILO, LUCIANA ; CARNEIRO, LETICIA DE A.M ; JANDRE, Frederico ; PINO, ALEXANDRE V. ;

Giannella-Neto, Antonio ; Zin, Walter A. ; CORRÊA, LEONARDO HOLANDA TRAVASSOS ; SOUZA, MARCIO NOGUEIRA DE ;

Carvalho, Alysson R. . Does acute exposure to aldehydes impair pulmonary function and structure?. Respiratory Physiology &

Neurobiology, v. 229, p. 34-42, 2016. http://dx.doi.org/10.1016/j.resp.2016.04.002

2. ALBERCA-CUSTÓDIO, RICARDO WESLEY ; GREIFFO, FLÁVIA REGINA ; MACKENZIE, BREANNE ; OLIVEIRA-JUNIOR,

MANOEL CARNEIRO ; ANDRADE-SOUSA, ADILSON SANTOS ; GRAUDENZ, GUSTAVO SILVEIRA ; SANTOS, ANGELA

BATISTA GOMES ; DAMACENO-RODRIGUES, NILSA REGINA ; CASTRO-FARIA-NETO, HUGO CAIRE ; ARANTES-COSTA,

FERNANDA MAGALHAES ; MARTINS, MILTON DE ARRUDA ; ABBASI, ASGHAR ; LIN, CHIN JIA ; IDZKO, MARCO ;

LIGEIRO OLIVEIRA, ANA PAULA ; NORTHOFF, HINNAK ; VIEIRA, RODOLFO PAULA . Aerobic Exercise Reduces Asthma

Phenotype by Modulation of the Leukotriene Pathway. Frontiers in Immunology (Online), v. 7, p. eCollection 201, 2016.


3. ASSUNÇÃO, LEONARDO SANTOS ; MAGALHÃES, KELLY G. ; CARNEIRO, ALAN BRITO ; MOLINARO, RAPHAEL ;

ALMEIDA, PATRÍCIA E. ; ATELLA, GEORGIA C. ; CASTRO-FARIA-NETO, HUGO C. ; BOZZA, PATRÍCIA T. . Schistosomal-

derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms. Biochimica and

Biophysica Acta. Molecular and Cell Biology of Lipids, v. 2, p. 1862(2):246-254, 2016. http://dx.doi.org/10.1016/j.bbalip.2016.11.006

4. BANDEIRA, ELGA ; LOPES-PACHECO, MIQUÉIAS ; CHIARAMONI, NADIA ; FERREIRA, DÉBORA ; FERNANDEZ-RUOCCO,

MARIA J. ; PRIETO, MARIA J. ; MARON-GUTIERREZ, TATIANA ; PERROTTA, RAMIRO M. ; DE CASTRO-FARIA-NETO,

HUGO C. ; ROCCO, PATRICIA R. M. ; ALONSO, SILVIA DEL VALLE ; MORALES, MARCELO M. . Association with Amino

Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery. Frontiers in Physiology, v. 7, p.

26;7:151, 2016. http://dx.doi.org/10.3389/fphys.2016.00151

5. BARRETO, MIRIAM MENNA ; RODRIGUES, ROSANA SOUZA . The importance of computed tomography of the chest in cases of

suspected infection with nontuberculous mycobacteria (Mycobacterium kansasii). RB. Radiologia Brasileira (Online), v. 49, p. V-V, 2016.

http://dx.doi.org/10.1590/0100-3984.2016.49.4e1

6. BOZZA, FERNANDO A.; GRINSZTEJN, BEATRIZ . Key points on Zika infection for the intensivist. Intensive Care Medicine (Print),

v. 00, p. 00, 2016. http://dx.doi.org/10.1007/s00134-016-4378-4

7. CARVALHO, G.M. ; Oliveira, V.R. ; CASQUILHO, N. V. ; ARAUJO, A. C. P. ; SOARES, R. M. ; AZEVEDO, S. M. F. O. ; PIRES,

KARLA MARIA PEREIRA ; VALENCA, SAMUEL SANTOS ; ZIN, W.A . Pulmonary and hepatic injury after sub-chronic exposure to

sublethal doses of microcystin-LR. Toxicon (Oxford), v. 112, p. 51-58, 2016. http://dx.doi.org/10.1016/j.toxicon.2016.01.066

8. CAVALCANTI, ALEXANDRE B. ; BOZZA, FERNANDO AUGUSTO ; MACHADO, FLAVIA R. ; SALLUH, JORGE I. F. ;

CAMPAGNUCCI, VALQUIRIA PELISSER ; VENDRAMIM, PATRICIA ; GUIMARAES, HELIO PENNA ; NORMILIO-SILVA,

KARINA ; DAMIANI, LUCAS PETRI ; ROMANO, EDSON ; CARRARA, FERNANDA ; LUBARINO DINIZ DE SOUZA, JULIANA

; SILVA, ALINE REIS ; RAMOS, GRAZIELLE VIANA ; TEIXEIRA, CASSIANO ; BRANDÃO DA SILVA, NILTON ; CHANG,

CHUNG-CHOU H. ; ANGUS, DEREK C. ; BERWANGER, OTAVIO . Effect of a Quality Improvement Intervention With Daily Round

Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients. JAMA (Chicago, Ill.), v. 315, p. 1480, 2016.

http://dx.doi.org/10.1001/jama.2016.3463

9. CAVALCANTI, ALEXANDRE B. ; DAMIANI, LUCAS P. ; BOZZA, FERNANDO A. . Acute Kidney Injury With Buffered

Crystalloids vs Saline Among ICU Patients. JAMA (Chicago, Ill.), v. 315, p. 1520, 2016. http://dx.doi.org/10.1001/jama.2016.0154

10. CERBINO-NETO, JOSÉ ; MESQUITA, EMERSOM CICILINI ; SOUZA, THIAGO MORENO L. ; PARREIRA, VIVIANE ; WITTLIN,

BERNARDO BASTOS ; DUROVNI, BETINA ; LEMOS, MARIA CRISTINA FERREIRA ; VIZZONI, ALEXANDRE ; BISPO DE

FILIPPIS, ANA MARIA ; SAMPAIO, SIMONE ALVES ; GONÇALVES, BIANCA DE SANTIS ; BOZZA, FERNANDO A. . Clinical

Manifestations of Zika Virus Infection, Rio de Janeiro, Brazil, 2015. Emerging Infectious Diseases (Print), v. 22, p. 15;22(6), 2016.

http://dx.doi.org/10.3201/eid2207.160375

11. COSTA CARVALHO, JORGE LUIS ; DE BRITO, AURILÉIA APARECIDA ; DE OLIVEIRA, ANA PAULA LIGEIRO ; DE

CASTRO FARIA NETO, HUGO CAIRE ; PEREIRA, THIAGO MARTINI ; DE CARVALHO, REGIANE ALBERTINI ;

ANATRIELLO, ELEN ; AIMBIRE, FLÁVIO . The chemokines secretion and the oxidative stress are targets of low-level laser therapy in

allergic lung inflammation. J BIOPHOTONICS, v. 1, p. 1, 2016. http://dx.doi.org/10.1002/jbio.201600061

12. CRUZ, FERNANDA FERREIRA ; HORTA, LUCAS FELIPE BASTOS ; MAIA, LÍGIA DE ALBUQUERQUE ; LOPES-PACHECO,

MIQUÉIAS ; SILVA, ANDRÉ BENEDITO DA ; MORALES, MARCELO MARCO ; GONÇALVES-DE-ALBUQUERQUE,

CASSIANO FELIPPE ; TAKIYA, CHRISTINA MAEDA ; DE CASTRO-FARIA-NETO, HUGO CAIRE ; ROCCO, PATRICIA

RIEKEN MACEDO . Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis. Plos One, v. 11, p. e0147005,


13. DE AZEVEDO-QUINTANILHA, ISACLAUDIA G. ; VIEIRA-DE-ABREU, ADRIANA ; FERREIRA, ANDRÉ COSTA ;

NASCIMENTO, DANIELE O. ; SIQUEIRA, ALESSANDRA M. ; CAMPBELL, ROBERT A. ; TEIXEIRA FERREIRA, TATIANA P. ;

GUTIERREZ, TATIANA M. ; RIBEIRO, GABRIEL M. ; E SILVA, PATRICIA M. R. ; Carvalho, Alysson R. ; BOZZA, PATRICIA T. ;

ZIMMERMAN, GUY A. ; CASTRO-FARIA-NETO, HUGO C. . Integrin αDβ2 (CD11d/CD18) mediates experimental malaria-

associated acute respiratory distress syndrome (MA-ARDS). Malaria Journal (Online), v. 15, p. 393, 2016.SHARSHAR, TAREK ;

POLITO, ANDREA ; BOZZA, FERNANDO ; CHRÉTIEN, FABRICE . Statins and brain dysfunction in intensive care. LANCET RESP

MED, v. 4, p. 169-170, 2016. http://dx.doi.org/10.1186/s12936-016-1447-7

14. FORTUNATO, JUCÉLIA JEREMIAS ; DA ROSA, NAIANA ; LAURENTINO, ANA OLÍVIA MARTINS ; GOULART, MARINA ;

MICHALAK, CAMILA ; BORGES, LIDIANE PINTO ; CITTADIN SOARES, EVANDRO DA CRUZ ; REIS, PATRICIA ALVES ; DE

CASTRO FARIA NETO, HUGO CAIRE ; PETRONILHO, FABRÍCIA . Effects of Omega-3 Fatty Acids on Stereotypical Behavior and

Social Interactions in Wistar Rats Prenatally Exposed to Lipopolysaccarides. Nutrition (Burbank, Los Angeles County, Calif.), v. 0000, p.

00000, 2016. http://dx.doi.org/10.1016/j.nut.2016.10.019

15. GANDARA, A. C. ; NUNES, R. D. ; OLIVEIRA, J. H. ; DIAS, F. A. ; GONCALVES, R. L. S. ; HECHT, F. ; FERNANDES, D. C. ;

GENTA, F. A. ; LAURINDO, F. R. M. ; OLIVEIRA M.F. ; P.L. OLIVEIRA . Amino acids from blood proteins trigger downregulation of

superoxide via TORC pathway in the midgut of the Chagas disease vector Rhodnius prolixus. Bioscience Reports, v. 36, p. e321, 2016.

http://dx.doi.org/10.1042/BSR20160061

16. GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; MEDEIROS-DE-MORAES, ISABEL MATOS ; OLIVEIRA, FLORA

MAGNO DE JESUS ; BURTH, PATRÍCIA ; BOZZA, PATRÍCIA TORRES ; CASTRO FARIA, MAURO VELHO ; SILVA,

ADRIANA RIBEIRO ; CASTRO-FARIA-NETO, HUGO CAIRE DE . Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases

Organ Dysfunction and Mortality in Experimental Sepsis. Plos One, v. 11, p. e0153607, 2016.


17. JONES, A. ; MESHULAM, T. ; OLIVEIRA M.F. ; BURRITT, N. ; CORKEY, B. E. . Extracellular Redox Regulation of Intracellular

Reactive Oxygen Generation, Mitochondrial Function and Lipid Turnover in Cultured Human Adipocytes. Plos One, v. 11, p. e0164011,


18. KAYNAR, ATA MURAT ; BAKALOV, VELI ; LAVERDE, SILVIA MARTINEZ ; CAMBRIEL, AMÉLIE I. F. ; LEE, BYOUNG-

HOON ; TOWHEED, ATIF ; GREGORY, ALYSSA D. ; WEBB, STEVEN A. R. ; PALLADINO, MICHAEL J. ; BOZZA, FERNANDO

A. ; SHAPIRO, STEVEN D. ; ANGUS, DEREK C. . Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila

melanogaster. Intensive Care Medicine Experimental, v. 4, p. 4(1):4, 2016. http://dx.doi.org/10.1186/s40635-016-0075-4

19. KENNEDY-FEITOSA, EMANUEL ; OKURO, RENATA TIEMI ; PINHO RIBEIRO, VANESSA ; LANZETTI, MANUELLA ;

BARROSO, MARINA VALENTE ; ZIN, WALTER ARAÚJO ; PORTO, LUÍS CRISTÓVÃO ; BRITO-GITIRANA, LYCIA ;

174


174

VALENCA, SAMUEL SANTOS . Eucalyptol attenuates cigarette smoke-induced acute lung inflammation and oxidative stress in the

mouse. Pulmonary Pharmacology & Therapeutics, v. 41, p. 11-18, 2016. http://dx.doi.org/10.1016/j.pupt.2016.09.004

20. LAKSHMIKANTH, CHIKKAMENAHALLI LAKSHMINARAYANA ; JACOB, SHANCY PETSEL ; KUDVA, AVINASH

KUNDADKA ; LATCHOUMYCANDANE, CALIVARATHAN ; YASHASWINI, PUTTARAJU SRIKANTA MURTHY ; SUMANTH,

MOSALE SEETHARAM ; GONCALVES-DE-ALBUQUERQUE, CASSIANO F. ; SILVA, ADRIANA R. ; SINGH, SRIDEVI

ANNAPURNA ; CASTRO-FARIA-NETO, HUGO C. ; PRABHU, SANDEEP KUMBLE ; MCINTYRE, THOMAS M. ; MARATHE,

GOPAL KEDIHITHLU . Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia - like pathology in Swiss albino mice. Scientific

Reports, v. 6, p. 34666, 2016. http://dx.doi.org/10.1038/srep34666

21. LAKSHMIKANTH, CHIKKAMENAHALLI LAKSHMINARAYANA ; JACOB, SHANCY PETSEL ; CHAITHRA, VYALA

HANUMANTHAREDDY ; DE CASTRO-FARIA-NETO, HUGO CAIRE ; MARATHE, GOPAL KEDIHITHLU . Sepsis: in search of

cure. Inflammation Research (Printed ed.), v. 65, p. 587-602, 2016. http://dx.doi.org/10.1007/s00011-016-0937-y

22. MAZZOLI-ROCHA, F. ; OLIVEIRA, V.R. ; BARCELLOS, B.C. ; MOREIRA, D.K.M. ; SALDIVA, P. H. N. ; FAFFE, D.S. ; ZIN, W.

A. . Time-dependency of mice lung recovery after a 4-week exposure to traffic or biomass air pollutants. Respiratory Physiology &

Neurobiology, v. 230, p. 16-21, 2016. http://dx.doi.org/10.1016/j.resp.2016.05.003

23. MedeirOS R ; PESSOLANI, M. ; SARNO, E. ; SOLA-PENNA, M. ; OLIVEIRA M.F. ; MORAES, M. ; LARA, F.A. . Subversion of

Schwann Cell Glucose Metabolism by Mycobacterium leprae. The Journal of Biological Chemistry (Print), v. 291, p. 21375-21387, 2016.


24. MOREIRA GOMES, MARIA D. ; CARVALHO, GIOVANNA M. C. ; CASQUILHO, NATALIA V. ; ARAÚJO, ANDRESSA C. P. ;

VALENÇA, SAMUEL S. ; LEAL-CARDOSO, JOSE H. ; ZIN, WALTER A. . 2,2'-Azobis (2-Amidinopropane) Dihydrochloride Is a

Useful Tool to Impair Lung Function in Rats. Frontiers in Physiology, v. 7, p. 475, 2016. http://dx.doi.org/10.3389/fphys.2016.00475

25. OLIVEIRA MP ; CORRÊA SOARES, JULIANA B. R. ; OLIVEIRA, M.F. . Sexual Preferences in Nutrient Utilization Regulate Oxygen

Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology. Plos


26. ON RANKE, FELIPE MUSSI ; PEREIRA FREITAS, HELOISA MARIA ; MANÇANO, ALEXANDRE DIAS ; RODRIGUES,

ROSANA SOUZA ; HOCHHEGGER, BRUNO ; ESCUISSATO, DANTE ; ARAUJO NETO, CESAR AUGUSTO ; DA SILVA,

THIAGO KRIEGER BENTO ; MARCHIORI, EDSON . Pulmonary Involvement in Niemann-Pick Disease: A State-of-the-Art Review.

Lung (New York), v. 194, p. 511-518, 2016. http://dx.doi.org/10.1007/s00408-016-9893-0

27. PAULA, LUIS FELIPE SANTOS DA CRUZ ; WELLMAN, TYLER J. ; WINKLER, TILO ; SPIETH, PETER MARKUS ; GÜLDNER,

ANDREAS ; VENEGAS, JOSE GABRIEL ; GAMA DE ABREU, MARCELO ; CARVALHO, ALYSSON RONCALLY ; VIDAL

MELO, MARCOS F. . Regional Tidal Lung Strain in Mechanically Ventilated Normal Lungs. Journal of Applied Physiology (1985), v.

XX, p. jap.00861.2015, 2016. http://dx.doi.org/10.1152/japplphysiol.00861.2015

28. PECEGO, ANA CARLA ; AMANCIO, RODRIGO T. ; RIBEIRO, CAMILA ; MESQUITA, Emersom Cicilini ; MEDEIROS, DENISE

M. ; CERBINO, JOSÉ ; GRINSZTEJN, BEATRIZ ; BOZZA, F. A. ; JAPIASSU, ANDRE M. . Six-month survival of critically ill

patients with HIV-related disease and tuberculosis: a retrospective study. BMC Infectious Diseases (Online), v. 16, p. 270, 2016.

http://dx.doi.org/10.1186/s12879-016-1644-6

29. PEREIRA, PAULO ROGERIO ; OLIVEIRA-JUNIOR, MANOEL CARNEIRO ; MACKENZIE, BREANNE ; CHIOVATTO, JAIME

EDUARDO DAVINO ; MATOS, YVES ; GREIFFO, FLAVIA REGINA ; RIGONATO OLIVEIRA, NICOLE CRISTINE ;

BRUGEMMAN, THAYSE REGINA ; DELLE, HUMBERTO ; IDZKO, MARCO ; ALBERTINI, REGIANE ; LIGEIRO OLIVEIRA,

ANA PAULA ; DAMACENO-RODRIGUES, NILSA REGINA ; CALDINI, ELIA GARCIA ; FERNANDEZ, ISIS ENSIL ; CASTRO-

FARIA-NETO, HUGO CAIRE ; DOLHNIKOFF, MARISA ; EICKELBERG, OLIVER ; VIEIRA, RODOLFO PAULA . Exercise

Reduces Lung Fibrosis Involving Serotonin/Akt Signaling. Medicine and Science in Sports and Exercise, v. 1, p. 1, 2016.

http://dx.doi.org/10.1249/mss.0000000000000907

30. REIS, P. A. ; CASTRO-FARIA-NETO, H. C. . Infection, inflammation, cognition: mediators, correlations, and implications.

Neurociências (Rio de Janeiro), v. 12, p. capa-01, 2016.

31. REIS, PATRICIA A. ; ALEXANDRE, PEDRO C.B. ; D?AVILA, JOANA C. ; SIQUEIRA, LUCIANA D. ; ANTUNES, BARBARA ;

ESTATO, VANESSA ; TIBIRIÇA, EDUARDO V. ; VERDONK, FRANCK ; SHARSHAR, TAREK ; CHRÉTIEN, FABRICE ;

CASTRO-FARIA-NETO, HUGO C. ; BOZZA, FERNANDO A. . Statins prevent cognitive impairment after sepsis by reverting

neuroinflammation, and microcirculatory/endothelial dysfunction. Brain, Behavior, and Immunity, v. 8, p. S0889-1591(16)3, 2016.

http://dx.doi.org/10.1016/j.bbi.2016.11.006

32. SALLES VON-HELD-VENTURA, JULIANA ; MÁZALA-DE-OLIVEIRA, THALITA ; CÂNDIDA DA ROCHA OLIVEIRA,

AMANDA ; GRANJA, MARCELO GOMES ; GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; CASTRO-FARIA-NETO,

HUGO CAIRE ; GIESTAL-DE-ARAUJO, ELIZABETH . The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β

and TNF-α. Biochemical and Biophysical Research Communications (Print), v. x, p. xxxx, 2016.

http://dx.doi.org/10.1016/j.bbrc.2016.07.043

33. SANDLIN, REBECCA D ; FONG, KIM Y ; Stiebler, Renata ; GULKA, CHRISTOPHER P ; NESBITT, JENNY E ; OLIVEIRA,

MATHEUS P ; OLIVEIRA, MARCUS F. ; WRIGHT, DAVID W. . Detergent-mediated formation of β-hematin: Heme crystallization

promoted by detergents implicates nanostructure formation for use as a biological mimic. Crystal Growth & Design, v. 16, p. 2542-2551,

2016. http://dx.doi.org/10.1021/acs.cgd.5b01580

34. SOUZA-DANTAS, VICENTE CÉS ; PÓVOA, PEDRO ; BOZZA, F. A. ; SOARES, MARCIO ; SALLUH, JI . Preventive strategies and

potential therapeutic interventions for delirium in sepsis. Hospital Practice, v. 1, p. 21548331.2016.1192453, 2016.

http://dx.doi.org/10.1080/21548331.2016.1192453

35. TORRENTES-CARVALHO, AMANDA ; HOTTZ, EUGÊNIO DAMACENO ; MARINHO, CINTIA FERREIRA ; DA SILVA,

JÉSSICA BADOLATO-CORRÊA ; DE OLIVEIRA PINTO, LUZIA MARIA ; FIALHO, LUCIANA GOMES ; BOZZA, FERNANDO

AUGUSTO ; CUNHA, RIVALDO VENÂNCIO ; DAMASCO, PAULO VIEIRA ; KUBELKA, CLAIRE FERNANDES ; DE

AZEREDO, ELZINANDES LEAL . Characterization of clinical and immunological features in patients coinfected with dengue virus and

HIV. Clinical Immunology (Orlando, Fla. Print), v. 164, p. 95-105, 2016. http://dx.doi.org/10.1016/j.clim.2016.01.005

36. VERDONK, FRANCK ; ROUX, PASCAL ; FLAMANT, PATRICIA ; FIETTE, LAURENCE ; BOZZA, FERNANDO A. ; SIMARD,

SÉBASTIEN ; LEMAIRE, MARC ; PLAUD, BENOIT ; SHORTE, SPENCER L. ; SHARSHAR, TAREK ; CHRÉTIEN, FABRICE ;

DANCKAERT, ANNE . Phenotypic clustering: a novel method for microglial morphology analysis. Journal of Neuroinflammation, v. 13,

p. 153, 2016. http://dx.doi.org/10.1186/s12974-016-0614-7


1. ALMEIDA, FRANCINE MARIA ; OLIVEIRA-JUNIOR, MANOEL CARNEIRO ; SOUZA, RENATO APARECIDO ; PETRONI,

RICARDO COSTA ; SOTO, SONIA FATIMA ; SORIANO, FRANCISCO GARCIA ; DE CARVALHO, PAULO TARSO CAMILLO ;

ALBERTINI, REGIANE ; DAMACENO-RODRIGUES, NILSA REGINA ; LOPES, FERNANDA DEGOBBI TENORIO QUIRINO SA

; CASTRO-FARIA-NETO, HUGO CAIRE ; MARTINS, MILTON ARRUDA ; DOLHNIKOFF, MARISA ; PAZETTI, ROGERIO ;

VIEIRA, RODOLFO PAULA . Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion

injury. The Journal of Heart and Lung Transplantation, v. 15, p. S1053-2498(15), 2015. http://dx.doi.org/10.1016/j.healun.2015.06.012

2. BARROSO, SHANA P. C. ; NICO, DIRLEI ; NASCIMENTO, DANIELLE ; SANTOS, ANA CLARA V. ; COUCEIRO, JOSÉ

NELSON S. S. ; BOZZA, FERNANDO A. ; FERREIRA, ANA M. A. ; FERREIRA, DAVIS F. ; PALATNIK-DE-SOUSA, CLARISA B.

; SOUZA, THIAGO MORENO L. ; GOMES, ANDRE M. O. ; SILVA, JERSON L.*; OLIVEIRA, ANDRÉA C. . Intranasal

Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice. Plos One, v. 10, p. e0128785,

2015. http://dx.doi.org/10.1371/journal.pone.0128785 *IN COLLABORATION WITH AL 1 (SILVA).

3. CABRAL, L. F. ; D'ELIA, T.C. ; MARINS, D. S. ; ZIN, W A ; GUIMARAES, F. S. . Pursed lip breathing improves exercise tolerance in

COPD: A randomized crossover study. European Journal of Physical and Rehabilitation Medicine (Testo Stampato), v. 51, p. 79-88, 2015.

175


175

4. CAMILO, G.B. ; CARVALHO, A.R.S. ; MACHADO, D.C. ; MOGAMI, R. ; KASUKI, L. ; GADELHA, M.R. ; MELO, P.L. ; LOPES,

A.J. . Correlations between forced oscillation technique parameters and pulmonary densitovolumetry values in patients with acromegaly.

Brazilian journal of medical and biological research, v. 48, p. 877-885, 2015.

5. CAMILO, GUSTAVO BITTENCOURT ; CARVALHO, ALYSSON RONCALLY SILVA ; MACHADO, DEQUITIER CARVALHO ;

MOGAMI, ROBERTO ; MELO, PEDRO LOPES ; LOPES, AGNALDO JOSÉ . CT pulmonary densitovolumetry in patients with

acromegaly: a comparison between active disease and controlled disease. British Journal of Radiology, v. 6, p. 20150315, 2015.

6. CORRÊA SOARES, JULIANA B. R. ; GAVIRAGHI A ; OLIVEIRA, M.F. . Mitochondrial Physiology in the Major Arbovirus Vector

Aedes aegypti: Substrate Preferences and Sexual Differences Define Respiratory Capacity and Superoxide Production. Plos One, v. 10, p.


7. DA CUNHA, LUIZ GONZAGA ; FERREIRA, MIRIAM FRANCISCA ; DE MORAES, JOÃO ALFREDO ; REIS, PATRICIA ALVES ;

CASTRO-FARIA-NETO, HUGO CAIRE ; BARJA-FIDALGO, CHRISTINA ; PLOTKOWSKI, MARIA-CRISTINA ; SALIBA,

ALESSANDRA MATTOS . ExoU-induced redox imbalance and oxidative stress in airway epithelial cells during Pseudomonas

aeruginosa pneumosepsis. Medical Microbiology and Immunology, v. 1, p. 25904542, 2015. http://dx.doi.org/10.1007/s00430-015-0418-x

8. FARIA, IGOR MURAD ; ZANETTI, GLÁUCIA ; BARRETO, MIRIAM MENNA ; RODRIGUES, ROSANA SOUZA ; ARAUJO-

NETO, CESAR AUGUSTO ; SILVA, JORGE LUIZ PEREIRA E ; ESCUISSATO, DANTE LUIZ ; SOUZA JR, ARTHUR SOARES ;

IRION, KLAUS LOUREIRO ; MANÇANO, ALEXANDRE DIAS ; NOBRE, LUIZ FELIPE ; HOCHHEGGER, BRUNO ;

MARCHIORI, EDSON . Organizing pneumonia: chest HRCT findings. Jornal Brasileiro de Pneumologia (Online), v. 41, p. 231-237,

2015. http://dx.doi.org/10.1590/s1806-37132015000004544

9. FRANCISCO, FLÁVIA ANGÉLICA FERREIRA ; RODRIGUES, ROSANA SOUZA ; BARRETO, MIRIAM MENNA ;

ESCUISSATO, DANTE LUIZ ; ARAUJO NETO, CESAR AUGUSTO ; SILVA, JORGE LUIZ PEREIRA E ; SILVA, CLAUDIO S. ;

HOCHHEGGER, BRUNO ; SOUZA JR., ARTHUR SOARES ; ZANETTI, GLÁUCIA ; MARCHIORI, EDSON . Can chest high-

resolution computed tomography findings diagnose pulmonary alveolar microlithiasis?. RB. Radiologia Brasileira (Online), v. 48, p. 205-

210, 2015. http://dx.doi.org/10.1590/0100-3984.2014.0123

10. GARCIA, DIOGO GOMES ; CASTRO-FARIA-NETO, HUGO CAIRE DE ; SILVA, CAMILA IGNÁCIO DA ; SOUZA E SOUZA,

KAUÊ FRANCISCO CORREA DE ; GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; SILVA, ADRIANA RIBEIRO ;

AMORIM, LIDIA MARIA DA FONTE DE ; FREIRE, ALINE SOARES ; SANTELLI, RICARDO ERTHAL ; DINIZ, LUAN PEREIRA

; GOMES, FLÁVIA CARVALHO ALCANTARA ; FARIA, MAURO VELHO DE CASTRO ; BURTH, PATRÍCIA . Na/K-ATPase as a

target for anticancer drugs: studies with perillyl alcohol. Molecular Cancer, v. 14, p. 15;14(1):105., 2015.

http://dx.doi.org/10.1186/s12943-015-0374-5

11. GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; SILVA, ADRIANA RIBEIRO ; BURTH, PATRÍCIA ; CASTRO-

FARIA, MAURO VELHO ; CASTRO-FARIA-NETO, HUGO CAIRE . Acute Respiratory Distress Syndrome: Role of Oleic Acid-

Triggered Lung Injury and Inflammation. Mediators of Inflammation (Print), v. 2015, p. 1-9, 2015. http://dx.doi.org/10.1155/2015/260465

12. HOCHHEGGER, BRUNO ; SOUZA, VINÍCIUS VALÉRIO SILVEIRA DE ; MARCHIORI, EDSON ; IRION, KLAUS LOUREIRO ;

SOUZA JR., ARTHUR SOARES ; ELIAS JUNIOR, JORGE ; RODRIGUES, ROSANA SOUZA ; BARRETO, MIRIAM MENNA ;

ESCUISSATO, DANTE LUIZ ; MANÇANO, ALEXANDRE DIAS ; ARAUJO NETO, CÉSAR AUGUSTO ; GUIMARÃES, MARCOS

DUARTE ; NIN, CARLOS SCHULER ; SANTOS, MARCEL KOENIGKAM ; SILVA, JORGE LUIZ PEREIRA E . Chest magnetic

resonance imaging: a protocol suggestion. RB. Radiologia Brasileira (Online), v. 48, p. 373-380, 2015. http://dx.doi.org/10.1590/0100-

3984.2014.0017

13. HOTTZ, EUGENIO D. ; MONTEIRO, ANA PAULA T. ; BOZZA, FERNANDO A. ; BOZZA, PATRÍCIA T. . Inflammasome in

Platelets: Allying Coagulation and Inflammation in Infectious and Sterile Diseases?. Mediators of Inflammation (Print), v. 2015, p. 1-7,

2015. http://dx.doi.org/10.1155/2015/435783

14. LOPES, A J ; MOGAMI, R ; CAMILO, G B ; MACHADO, D C ; MELO, P L ; CARVALHO, A R S . Relationships between the

pulmonary densitometry values obtained by CT and the forced oscillation technique parameters in patients with silicosis. British Journal

of Radiology, v. 88, p. 20150028, 2015.

15. MENNA BARRETO, MIRIAM ; MARCHIORI, EDSON ; DE BRITO, ANDREA ; ESCUISSATO, DANTE LUIZ ; HOCHHEGGER,

BRUNO ; SOUZA, ARTHUR SOARES ; RODRIGUES, ROSANA SOUZA . CT morphological features of the reversed halo sign in

pulmonary paracoccidioidomycosis. British Journal of Radiology, v. 88, p. 20150246, 2015. http://dx.doi.org/10.1259/bjr.20150246

16. NUSSBAUM, CLAUDIA ; BANNENBERG, SARAH ; KEUL, PETRA ; GRÄLER, MARKUS H. ; GONÇALVES-DE-

ALBUQUERQUE, CASSIANO F. ; KORHONEN, HANNA ; VON WNUCK LIPINSKI, KARIN ; HEUSCH, GERD ; DE CASTRO

FARIA NETO, HUGO C. ; ROHWEDDER, INA ; GÖTHERT, JOACHIM R. ; PRASAD, VYSAKH PUSHPA ; HAUFE, GÜNTER ;

LANGE-SPERANDIO, BAERBEL ; OFFERMANNS, STEFAN ; SPERANDIO, MARKUS ; LEVKAU, BODO . Sphingosine-1-

phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin. Nature Communications, v. 6, p. 6416, 2015.

http://dx.doi.org/10.1038/ncomms7416

17. OLIVEIRA, V. R. ; AVILA, M.B. ; CARVALHO, G.M. ; AZEVEDO, S. M. F. O. ; LIMA, L. M. ; BARREIRO, E. J. L. ; CARVALHO,

A.R. ; ZIN, W. A. . Investigating the therapeutic effects of LASSBio-596 in an in vivo model of cylindrospermopsin-induced lung injury.

Toxicon (Oxford), v. 94, p. 29-35, 2015. http://dx.doi.org/10.1016/j.toxicon.2014.12.004

18. OLIVEIRA, VINÍCIUS R. ; MANCIN, VIVIANE G.L. ; PINTO, ELIETE F. ; SOARES, RAQUEL M. ; AZEVEDO, SANDRA M.F.O. ;

MACCHIONE, MARIANGELA ; CARVALHO, ALYSSON R. ; ZIN, WALTER A. . Repeated intranasal exposure to microcystin-LR

affects lungs but not nasal epithelium in mice. Toxicon (Oxford), v. 104, p. 14-18, 2015.

19. PALMA, MARIANA L. ; ZAMITH-MIRANDA, DANIEL ; MARTINS, FLAVIANO S. ; BOZZA, FERNANDO A. ; NIMRICHTER,

LEONARDO ; MONTERO-LOMELI, MÔNICA ; MARQUES, ERNESTO T. A. ; DOURADINHA, BRUNO . Probiotic Saccharomyces

cerevisiae strains as biotherapeutic tools: is there room for improvement?. Applied Microbiology and Biotechnology, v. 99, p. 6563-6570,

2015. http://dx.doi.org/10.1007/s00253-015-6776-x

20. PARENTE, DANIELLA BRAZ ; PAIVA, FERNANDO FERNANDES ; OLIVEIRA NETO, JAIME ARAÚJO ; MACHADO-SILVA,

LILIAN ; FIGUEIREDO, FATIMA APARECIDA FERREIRA ; LANZONI, VALERIA ; CAMPOS, CARLOS FREDERICO

FERREIRA ; DO BRASIL, PEDRO EMMANUEL ALVARENGA AMERICANO ; GOMES, MARILIA DE BRITO ; PEREZ,

RENATA DE MELLO ; RODRIGUES, ROSANA SOUZA . Intravoxel Incoherent Motion Diffusion Weighted MR Imaging at 3.0 T:

Assessment of Steatohepatitis and Fibrosis Compared with Liver Biopsy in Type 2 Diabetic Patients. Plos One, v. 10, p. e0125653, 2015.


21. RABELLO, LÍGIA ; CONCEIÇÃO, CATARINA ; EBECKEN, KATIA ; LISBOA, THIAGO ; BOZZA, FERNANDO AUGUSTO ;

SOARES, MÁRCIO ; PÓVOA, PEDRO ; SALLUH, JORGE IBRAIN FIGUEIRA . Management of severe community-acquired

pneumonia in Brazil: a secondary analysis of an international survey. Revista Brasileira de Terapia Intensiva (Impresso), v. 27, p. 57-63,

2015. http://dx.doi.org/10.5935/0103-507x.20150010

22. ROCHAEL, NATALIA C. ; GUIMARÃES-COSTA, ANDERSON B. ; NASCIMENTO, MICHELLE T. C. ; DESOUZA-VIEIRA,

THIAGO S. ; OLIVEIRA, MATHEUS P. ; GARCIA E SOUZA, LUIZ F. ; OLIVEIRA, MARCUS F. ; SARAIVA, ELVIRA M. .

Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites.

Scientific Reports, v. 5, p. 18302, 2015. http://dx.doi.org/10.1038/srep18302

23. ROTMAN, VIVIAN ; CARVALHO, ALYSSON RONCALLY ; RODRIGUES, ROSANA SOUZA ; MEDEIROS, DENISE MACHADO

; PINTO, EDUARDO COSTA ; BOZZA, FERNANDO AUGUSTO ; CARVALHO, CARLOS ROBERTO RIBEIRO . Effects of the

open lung concept following ARDSnet ventilation in patients with early ARDS. BMC Anesthesiology, v. 16, p. 40, 2015.

http://dx.doi.org/10.1186/s12871-016-0206-1

24. SALOMON, FERNANDA FROTTE BOPP ; BARRETO, MIRIAM MENNA ; ZANETTI, GLÁUCIA ; RODRIGUES, ROSANA

SOUZA ; GASPARETTO, EMERSON LEANDRO ; MARCHIORI, EDSON . CNS and cutaneous involvement in tuberous sclerosis

complex. Arquivos de Neuro-Psiquiatria (Online), v. 73, p. 813-813, 2015. http://dx.doi.org/10.1590/0004-282x20150101

25. SCHREITER, DIERK ; CARVALHO, NADJA C. ; KATSCHER, SEBASTIAN ; MENDE, LUDGER ; RESKE, ALEXANDER P. ;

SPIETH, PETER M. ; CARVALHO, ALYSSON R. ; BEDA, ALESSANDRO ; LACHMANN, BURKHARD ; AMATO, MARCELO B.

P. ; WRIGGE, HERMANN ; RESKE, ANDREAS W. . Experimental blunt chest trauma - cardiorespiratory effects of different

mechanical ventilation strategies with high positive end-expiratory pressure: a randomized controlled study. BMC Anesthesiology, v. 16,

p. 3-1, 2015.

176


176

26. SERAFIM, RODRIGO B. ; BOZZA, FERNANDO A. ; SOARES, MARCIO ; DO BRASIL, PEDRO EMANUEL A.A. ; TURA,

BERNARDO R. ; ELY, E. WESLEY ; SALLUH, JORGE I.F. . Pharmacologic Prevention and Treatment of Delirium in Intensive Care

Patients: A Systematic Review. Journal of Critical Care, v. 15, p. S0883-9441(15)0, 2015. http://dx.doi.org/10.1016/j.jcrc.2015.04.005

27. SHINOTSUKA, CÁSSIA ; BOZZA, MARCELO ; OLIVEIRA, MARCUS ; BOZZA, FERNANDO . Mollecular, cellular and clinical

aspects of intracerebral hemorrhage: are the enemies within?. Current Neuropharmacology, v. 14, p. 1-1, 2015.

http://dx.doi.org/10.2174/1570159x14666151230110058

28. SOARES, MARCIO ; BOZZA, F. A. ; Angus, Derek C. ; JAPIASSÚ, ANDRÉ M. ; VIANA, WILLIAM N. ; COSTA, ROBERTO ;

BRAUER, LEONARDO ; MAZZA, BRUNO F. ; CORRÊA, THIAGO D. ; NUNES, ANDRÉ L. B. ; Lisboa, Thiago ; COLOMBARI,

FERNANDO ; MACIEL, ALEXANDRE T. ; AZEVEDO, LUCIANO C. P. ; DAMASCENO, MOYZÉS ; FERNANDES, HAGGEAS S.

; CAVALCANTI, ALEXANDRE B. ; DO BRASIL, PEDRO E. A. A. ; KAHN, JEREMY M. ; SALLUH, JI . Organizational

characteristics, outcomes, and resource use in 78 Brazilian intensive care units: the ORCHESTRA study. Intensive Care Medicine (Print),

v. 41, p. 2149-2160, 2015. http://dx.doi.org/10.1007/s00134-015-4076-7

29. SOUZA, THIAGO MORENO LOPES E ; FINTELMAN-RODRIGUES, NATALIA ; RESENDE, PAOLA CRISTINA ; MESQUITA,

MILENE ; GREGIANINI, TATIANA SCHAFFER ; Bozza, Fernando A ; PECEGO, ANA CARLA ; FERNANDES, SANDRA

BIANCHINI ; CURY, ANA LUISA FURTADO ; RIEDIGER, IRINA NASTASSJA ; SIQUEIRA, MARILDA M . Oseltamivir-resistant

influenza A(H1N1)pdm2009 strains found in Brazil are endowed with permissive mutations, which compensate the loss of fitness

imposed by antiviral resistance. Memórias do Instituto Oswaldo Cruz (Impresso), v. 00, p. 00-00, 2015. http://dx.doi.org/10.1590/0074-

02760140330

30. TORRES, VIVIANE BL ; AZEVEDO, LUCIANO CP ; SILVA, ULYSSES VA ; CARUSO, PEDRO ; TORELLY, ANDRÉ P ; SILVA,

ELIEZER ; CARVALHO, FREDERICO B ; VIANNA, ARTHUR ; SOUZA, PAULO CP ; GODOY, MICHELE MG ; AZEVEDO, JOSÉ

RA ; SPECTOR, NELSON ; BOZZA, FERNANDO A ; SALLUH, JORGE IF ; SOARES, MARCIO . Sepsis-Associated Outcomes in

Critically Ill Patients with Malignancies. Annals of the American Thoracic Society, v. 12, p. 150618124156002, 2015.

http://dx.doi.org/10.1513/annalsats.201501-046oc

31. WOLF, SAMUEL J. ; RESKE, ALEXANDER P. ; HAMMERMÜLLER, SÖREN ; COSTA, EDUARDO L. V. ; SPIETH, PETER M. ;

HEPP, PIERRE ; CARVALHO, ALYSSON R. ; KRAßLER, JENS ; WRIGGE, HERMANN ; AMATO, MARCELO B. P. ; RESKE,

ANDREAS W. . Correlation of Lung Collapse and Gas Exchange - A Computer Tomographic Study in Sheep and Pigs with Atelectasis in

Otherwise Normal Lungs. Plos One, v. 10, p. e0135272, 2015.


1. AJCEVIC, M. ; LUCANGELO, U. ; FERLUGA, M. ; ZIN, W. A. ; ACCARDO, A. . In vitro estimation of pressure drop across tracheal

tubes during high-frequency percussive ventilation. Physiological Measurement (Print), v. 35, p. 177-188, 2014.

http://dx.doi.org/10.1088/0967-3334/35/2/177

2. ALMEIDA, ISABEL C. T. ; SOARES, MÁRCIO ; BOZZA, FERNANDO A. ; SHINOTSUKA, CASSIA RIGHY ; BUJOKAS,

RENATA ; SOUZA-DANTAS, VICENTE CÉS ; ELY, E. WESLEY ; SALLUH, JORGE I. F. . The Impact of Acute Brain Dysfunction

in the Outcomes of Mechanically Ventilated Cancer Patients. Plos One, v. 9, p. e85332, 2014.


3. AUSTIN, SHAMLY ; MURTHY, SRINIVAS ; WUNSCH, HANNAH ; ADHIKARI, NEILL K. J. ; KARIR, VEENA ; ROWAN,

KATHRYN ; JACOB, SHEVIN T. ; SALLUH, JI ; Salluh, Jorge ; BOZZA, F. A. ; DU, BIN ; AN, YOUZHONG ; LEE, BRUCE ; WU,

FELICIA ; NGUYEN, YEN-LAN ; OPPONG, CHRIS ; VENKATARAMAN, RAMESH ; VELAYUTHAM, VIMALRAJ ; DUEÑAS,

CARMELO ; Angus, Derek C. . Access to urban acute care services in high- vs. middle-income countries: an analysis of seven cities.

Intensive Care Medicine (Print), v. 40, p. 342-352, 2014. http://dx.doi.org/10.1007/s00134-013-3174-7

4. AZEVEDO, LUCIANO C. P. ; CARUSO, PEDRO ; SILVA, ULYSSES V. A. ; TORELLY, ANDRÉ P. ; SILVA, ELIÉZER ;

REZENDE, EDERLON ; NETTO, JOSÉ J. ; PIRAS, CLAUDIO ; LOBO, SUZANA M. A. ; KNIBEL, MARCOS F. ; TELES, JOSÉ M.

M. ; LIMA, RICARDO A. ; FERREIRA, BRUNO S. ; FRIEDMAN, GILBERTO ; REA-NETO, ALVARO ; DAL-PIZZOL, FELIPE ;

BOZZA, F. A. ; SALLUH, JI ; SALLUH, JORGE I. F. ; SOARES, MÁRCIO . Outcomes for Patients with Cancer Admitted to the ICU

Requiring Ventilatory Support: Results from a Prospective Multicenter Study. Chest (American College of Chest Physicians), v. 1, p. 1,

2014. http://dx.doi.org/10.1378/chest.13-1870

5. BARBIERI, RAQUEL RODRIGUES ; SALES, ANNA MARIA ; ILLARRAMENDI, XIMENA ; MORAES, MILTON OZÓRIO ;

NERY, JOSÉ AUGUSTO DA COSTA ; MOREIRA, SUELEN JUSTO MARIA ; SARNO, EUZENIR NUNES ; MACHADO, ALICE

DE MIRANDA ; BOZZA, FERNANDO AUGUSTO . Diagnostic challenges of single plaque-like lesion paucibacillary leprosy.

Memórias do Instituto Oswaldo Cruz (Impresso), v. 109, p. 944-947, 2014. http://dx.doi.org/10.1590/0074-0276140212

6. BEDA, A. ; GUELDNER, A. ; CARVALHO, A.R. ; ZIN, W. A. ; CARVALHO, N. C. ; HUHLE, R. ; GIANNELLA NETO, A. ; KOCH,

T. ; GAMA-DE-AREU, M. . Liquid- and Air-Filled Catheters without Balloon as an Alternative to the Air-Filled Balloon Catheter for

Measurement of Esophageal Pressure. Plos One, v. 9, p. e103057, 2014. http://dx.doi.org/10.1371/journal.pone.0103057

7. BEDA, ALESSANDRO ; GÜLDNER, ANDREAS ; CARVALHO, ALYSSON R. ; ZIN, WALTER ARAUJO ; CARVALHO, NADJA

C. ; HUHLE, ROBERT ; GIANNELLA-NETO, ANTONIO ; KOCH, THEA ; DE ABREU, MARCELO GAMA . Liquid- and Air-Filled

Catheters without Balloon as an Alternative to the Air-Filled Balloon Catheter for Measurement of Esophageal Pressure. Plos One, v. 9, p.

e103057, 2014.

8. BEDA, ALESSANDRO ; SIMPSON, DAVID M. ; CARVALHO, NADJA C. ; CARVALHO, ALYSSON RONCALLY S. . Low-

frequency heart rate variability is related to the breath-to-breath variability in the respiratory pattern. Psychophysiology (New York. Print),

v. 51, p. n/a-n/a, 2014.

9. BELÉM, LUCIANA CAMARA ; ZANETTI, GLÁUCIA ; SOUZA, ARTHUR SOARES ; HOCHHEGGER, BRUNO ; GUIMARÃES,

MARCOS DUARTE ; NOBRE, LUIZ FELIPE ; RODRIGUES, ROSANA SOUZA ; MARCHIORI, EDSON . Metastatic pulmonary

calcification: State-of-the-art review focused on imaging findings. Respiratory Medicine, v. 2, p. 1, 2014.

http://dx.doi.org/10.1016/j.rmed.2014.01.012

10. BOZZA, F. A.; SALLUH, JI ; LISBOA, THIAGO ; SOARES, M. ; POVOA, PEDRO . Management of severe community-acquired

pneumonia: A survey on the attitudes of 468 physicians in Iberia and South America. Journal of Critical Care, p. 00, 2014.

http://dx.doi.org/10.1016/j.jcrc.2014.05.019

11. CAMILO, L.M. ; AVILA, M.B. ; PAULA, L.F.S.C. ; RIBEIRO, G.C.M. ; SPIETH, P. M. ; RESKE, A. A. ; AMATO, M. B. P. ;

GIANNELLA NETO, A. ; ZIN, W. A. ; CARVALHO, A.R. . Positive End-Expiratory Pressure and Variable Ventilation in Lung-Healthy

Rats under General Anesthesia. Plos One, v. 9, p. e110817, 2014. http://dx.doi.org/10.1371/journal.pone.0110817

12. CARVALHO, G.M. ; NAGATO, L. K. S. ; FAGUNDES, S.S. ; SANTOS, F. B. ; CALHEIROS, A. S. ; MALM, O. ; BOZZA, P. T. ;

SALDIVA, PAULO H.N. ; FAFFE, DÉBORA S. ; ROCCO, PATRICIA R. M. ; ZIN, W. A. . Time course of pulmonary burden in mice

exposed to residual oil fly ash. Frontiers in Physiology, v. 5, p. 366, 2014. http://dx.doi.org/10.3389/fphys.2014.00366

13. COMUZZI, L. ; RONCALLY-CARVALHO, A. ; LUCANGELO, U. ; ZIN, W. A. . Artificial Ventilation During Pneumoperitoneum.

Shortness of Breath, v. 3, p. 58-67, 2014.

14. COSTANZA, ANNELISE C. ; MOSCAVITCH, SAMUEL D. ; FARIA NETO, HUGO C.C. ; MESQUITA, EVANDRO T. . Probiotic

therapy with Saccharomyces boulardii for heart failure patients: a randomized, double-blind, placebo-controlled pilot trial. International

Journal of Cardiology (Print), v. 4, p. 2014.11.034, 2014. http://dx.doi.org/10.1016/j.ijcard.2014.11.034

15. CRUZ, M. R. ; CAMILO, L. M. ; PAULA, L. F. ; JAPIASSU, A. M. ; BEDA, A. ; CARVALHO, AR ; BOZZA, F. A. ; MEDEIROS, D.

M. . Effects of Different Levels of Pressure Support on Intra-Individual Breath-to-Breath Variability. Respiratory Care, v. 12, p. 134,

2014. http://dx.doi.org/10.4187/respcare.02853

16. GARCIA-SOUZA, LUIZ F. ; OLIVEIRA M.F. . Mitochondria: Biological roles in platelet physiology and pathology. International

Journal of Biochemistry & Cell Biology, p. 156-160, 2014. http://dx.doi.org/10.1016/j.biocel.2014.02.015

17. GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; BURTH, PATRÍCIA ; SILVA, ADRIANA RIBEIRO ; DE MORAES,

ISABEL MATOS ; DE OLIVEIRA, FLORA MAGNO ; SANTELLI, RICARDO ERTHAL ; FREIRE, ALINE SOARES ; YOUNES-

177


177

IBRAHIM, MAURICIO ; DE CASTRO-FARIA-NETO, HUGO CAIRE ; DE CASTRO-FARIA, MAURO VELHO . Na/K-ATPase assay

in the intact mice lung subjected to perfusion. BMC Research Notes, v. 7, p. 798, 2014. http://dx.doi.org/10.1186/1756-0500-7-798

18. HERNANDES, MARINA S ; D'AVILA, JOANA C ; TREVELIN, SILVIA C ; REIS, PATRICIA A ; KINJO, ERIKA R ; LOPES,

LUCIA R ; CASTRO-FARIA-NETO, HUGO C ; CUNHA, FERNANDO Q ; BRITTO, LUIZ RG ; BOZZA, FERNANDO A . The role

of Nox2-derived ROS in the development of cognitive impairment after sepsis. Journal of Neuroinflammation, v. 11, p. 36, 2014.

http://dx.doi.org/10.1186/1742-2094-11-36

19. HOTTZ, E. D. ; MEDEIROS-DE-MORAES, I. M. ; VIEIRA-DE-ABREU, A. ; DE ASSIS, E. F. ; VALS-DE-SOUZA, R. ; CASTRO-

FARIA-NETO, H. C. ; WEYRICH, A. S. ; ZIMMERMAN, G. A. ; BOZZA, F. A. ; BOZZA, P. T. . Platelet Activation and Apoptosis

Modulate Monocyte Inflammatory Responses in Dengue. The Journal of Immunology (1950), v. 11, p. 1400091-1400091, 2014.

http://dx.doi.org/10.4049/jimmunol.1400091

20. KENNEDY-FEITOSA, EMANUEL ; PINTO, RÔMULO FONSECA SANTOS ; PIRES, KARLA MARIA PEREIRA ; MONTEIRO,

ANA PAULA TEIXEIRA ; MACHADO, MARIANA NASCIMENTO ; SANTOS, JULIANA CARVALHO ; RIBEIRO, MARCELO

LIMA ; ZIN, WALTER ARAÚJO ; CANETTI, CLÁUDIO AZEVEDO ; ROMANA-SOUZA, BRUNA ; PORTO, LUÍS CRISTÓVÃO ;

VALENCA, SAMUEL SANTOS . The influence of 5-lipoxygenase on cigarette smoke-induced emphysema in mice. Biochimica et

Biophysica Acta. G, General Subjects (Print), v. 1840, p. 199-208, 2014. http://dx.doi.org/10.1016/j.bbagen.2013.09.028

21. LEO, LUCIANA M. ; ALMEIDA-CORRÊA, SUELLEN ; CANETTI, CLAUDIO A. ; AMARAL, OLAVO B. ; BOZZA, FERNANDO

A. ; PAMPLONA, FABRICIO A. . Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in

Mice. Plos One, v. 9, p. e85009, 2014. http://dx.doi.org/10.1371/journal.pone.0085009

22. LUCANGELO, U. ; GARUFI, G. ; MARRAS, E. ; FERLUGA, M. ; TURCHET, F. ; BERNABE, F. ; COMUZZI, L. ; BERLOT, G. ;

ZIN, W. A. . End-tidal versus manually-controlled low-flow anaesthesia. Journal of Clinical Monitoring and Computing, v. 28, p. 117-

121, 2014. http://dx.doi.org/10.1007/s10877-013-9516-8

23. LUNA-GOMES, TATIANA ; FILARDY, ALESSANDRA A. ; ROCHA, JULIANA DUTRA B. ; DECOTE-RICARDO, DEBORA ;

LAROCQUE-DE-FREITAS, ISABEL FERREIRA ; MORROT, ALEXANDRE ; BOZZA, PATRÍCIA T. ; CASTRO-FARIA-NETO,

HUGO C. ; DOSREIS, GEORGE A. ; NUNES, MARISE P. ; FREIRE-DE-LIMA, CÉLIO G. . Neutrophils Increase or Reduce Parasite

Burden in Trypanosoma cruzi-Infected Macrophages, Depending on Host Strain: Role of Neutrophil Elastase. Plos One, v. 9, p. e90582,


24. MACHADO, M.N. ; SCHMIDT, A.C. ; SALDIVA, PAULO H.N. ; FAFFE, D. S. ; ZIN, W. A. . Pulmonary Functional and

Morphological Damage after Exposure to Tripoli Dust. Respiratory Physiology & Neurobiology, v. 196, p. 17-24, 2014.

http://dx.doi.org/10.1016/j.resp.2014.02.007

25. MACHADO, MARIANA NASCIMENTO ; FIGUEROA, S.F. ; MAZZOLI-ROCHA, FLAVIA ; VALENCA, SAMUEL SANTOS ; ZIN,

W. A. . Papain-induced experimental pulmonary emphysema in male and female mice. Respiratory Physiology & Neurobiology, v. 200, p.

90-96, 2014.

26. MAZZOLI-ROCHA, FLAVIA ; CARVALHO, GIOVANNA M.C. ; LANZETTI, MANUELLA ; VALENÇA, SAMUEL S. ; SILVA,

LUIZ F.F. ; SALDIVA, PAULO H.N. ; ZIN, WALTER A. ; FAFFE, DÉBORA S. . Respiratory toxicity of repeated exposure to particles

produced by traffic and sugar cane burning. Respiratory Physiology & Neurobiology, v. 191, p. 106-113, 2014.


27. MIYAZAKI, YASUNARI ; VIEIRA-DE-ABREU, ADRIANA ; HARRIS, ESTELLE S. ; SHAH, AMRAPALI M. ; WEYRICH,

ANDREW S. ; CASTRO-FARIA-NETO, HUGO C. ; ZIMMERMAN, GUY A. . Integrin αDβ2 (CD11d/CD18) Is Expressed by Human

Circulating and Tissue Myeloid Leukocytes and Mediates Inflammatory Signaling. Plos One, v. 9, p. e112770, 2014.


28. MONÇÃO-RIBEIRO, L. C. ; FAFFE, D. S. ; SANTANA, P. T. ; VIEIRA, F. S. ; GRACA, C. L. A. L. ; MARQUES-DA-SILVA, C. ;

MACHADO, M.N. ; CARUSO-NEVES, C. ; ZIN, W. A. ; BOROJEVIC, R. ; TAKIYA, C.M. ; COUTINHO-SILVA, R. . P2X7 Receptor

Modulates Inflammatory and Functional Pulmonary Changes Induced by Silica. Plos One, v. 9, p. e110185, 2014.


29. NASCIMENTO, EDUARDO ; HOTTZ, EUGENIO ; GARCIA-BATES, TATIANA ; BOZZA, FERNANDO ; MARQUES, ERNESTO ;

BARRATT-BOYES, SIMON . Emerging Concepts in Dengue Pathogenesis: Interplay between Plasmablasts, Platelets and Complement

in Triggering Vasculopathy. Critical Reviews in Immunology, v. 34, p. 227-240, 2014.

http://dx.doi.org/10.1615/critrevimmunol.2014010212

30. NISIMURA, LINDICE MITIE ; ESTATO, VANESSA ; DE SOUZA, ELEN MELLO ; REIS, PATRICIA A. ; LESSA, MARCOS

ADRIANO ; CASTRO-FARIA-NETO, HUGO CAIRE ; PEREIRA, MIRIAN CLAUDIA DE SOUZA ; TIBIRIÇÁ, EDUARDO ;

GARZONI, LUCIANA RIBEIRO . Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice. PLoS Neglected Tropical

Diseases (Online), v. 8, p. e2998, 2014. http://dx.doi.org/10.1371/journal.pntd.0002998

31. NUNES, MARCELO VIEIRA LEÃO ; GIANNELLA-NETO, ANTONIO ; TAVARES, FREDERICO CAETANO JANDRE DE ASSIS .

Continuous positive airway pressure setups evaluated at simulated exercise conditions. Revista Brasileira de Engenharia Biomédica

(Impresso), v. 30, p. 173-178, 2014. http://dx.doi.org/10.1590/rbeb.2014.014

32. PARENTE, DANIELLA BRAZ ; RODRIGUES, ROSANA SOUZA ; PAIVA, FERNANDO FERNANDES ; OLIVEIRA NETO, JAIME

ARAÚJO ; MACHADO-SILVA, LILIAN ; LANZONI, VALERIA ; CAMPOS, CARLOS FREDERICO FERREIRA ; EIRAS-ARAUJO,

ANTONIO LUIS ; DO BRASIL, PEDRO EMMANUEL ALVARENGA AMERICANO ; GARTEISER, PHILIPPE ; DE BRITO

GOMES, MARILIA ; DE MELLO PEREZ, RENATA . Is MR Spectroscopy Really the Best MR-Based Method for the Evaluation of

Fatty Liver in Diabetic Patients in Clinical Practice?. Plos One, v. 9, p. e112574, 2014. http://dx.doi.org/10.1371/journal.pone.0112574

33. PEIXOTO, LILIA SILVA ; VALIANTE, PAULO MARCOS ; RODRIGUES, ROSANA SOUZA ; BARRETO, MIRIAM MENNA ;

ZANETTI, GLÁUCIA ; MARCHIORI, EDSON . An Unusual Cause of Tree-in-Bud Pattern: Pulmonary Intravascular Tumor Embolism

Caused by Chondrosarcoma. Lung (New York), v. 193, p. 151, 2014. http://dx.doi.org/10.1007/s00408-014-9659-5

34. PERÍGOLO-VICENTE, RAFAEL ; RITT, KAREN ; GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; CASTRO-FARIA-

NETO, HUGO CAIRE ; PAES-DE-CARVALHO, ROBERTO ; GIESTAL-DE-ARAUJO, ELIZABETH . IL-6, A1 and A2aR: a crosstalk

that modulates BDNF and induces neuroprotection. Biochemical and Biophysical Research Communications (Print), v. 01, p.

YBBRC32131, 2014. http://dx.doi.org/10.1016/j.bbrc.2014.05.036

35. RAMOS, G. V. ; GUARALDO, L. ; JAPIASSU, A. M. ; BOZZA, F. A. . Comparison of two databases to detect potential drug-drug

interactions between prescriptions of HIV/AIDS patients in critical care. Journal of Clinical Pharmacy and Therapeutics (Print), v. 40, p.

n/a-n/a, 2014. http://dx.doi.org/10.1111/jcpt.12222

36. RETAMAL, JAIME ; BERGAMINI, BRUNO ; CARVALHO, ALYSSON R ; BOZZA, FERNANDO A ; BORZONE, GISELLA ;

BORGES, JOÃO ; LARSSON, ANDERS ; HEDENSTIERNA, GÖRAN ; BUGEDO, GUILLERMO ; BRUHN, ALEJANDRO . Non-

lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation.

Critical Care (London. Print), v. 18, p. 505, 2014. http://dx.doi.org/10.1186/s13054-014-0505-1

37. RIBEIRO, SAYONARA R ; LUZ, PAULA M ; CAMPOS, DAYSE P ; MOREIRA, RONALDO I ; COELHO, LARA ; JAPIASSU,

ANDRÉ ; BOZZA, FERNANDO ; VELOSO, VALDILEA G ; CHENE, GENEVIEVE ; GRINSZTEJN, BEATRIZ . Incidence and

determinants of severe morbidity among HIV-infected patients from Rio de Janeiro, Brazil, 2000-2010. Antiviral Therapy (London), v. N,

p. N, 2014. http://dx.doi.org/10.3851/IMP2716

38. RODRIGUES, R. S.; FIGUEIREDO, F. A. F. ; ZANETTI, G ; MARCHIORI, E . Battery ingestion: an unusual cause of mediastinitis.

Jornal Brasileiro de Pneumologia (Impresso), v. 40, p. 582-583, 2014. http://dx.doi.org/10.1590/S1806-37132014000500016

39. RODRIGUES, ROSANA SOUZA ; BRUM, ANA LIVIA GARCIA ; PAES, MARCIANO VIANA ; PÓVOA, TIAGO FAJARDO ;

BASILIO-DE-OLIVEIRA, CARLOS ALBERTO ; MARCHIORI, EDSON ; BORGHI, DANIELLE PROVENÇANO ; RAMOS,

GRAZIELLE VIANA ; BOZZA, FERNANDO AUGUSTO . Lung in Dengue: Computed Tomography Findings. Plos One, v. 9, p.


40. SANT' ANNA JUNIOR, M. ; CARVALHAL, R.F. ; CARNEIRO, J.R.I. ; LAPA, M.S. ; ZIN, W.A. ; LUGON, J.R. ; GUIMARÃES, F.S.

. Associação entre a mecânica respiratória e função autonómica na obesidade mórbida. Revista Portuguesa de Pneumologia, v. 20, p. 31-

35, 2014. http://dx.doi.org/10.1016/j.rppneu.2013.06.009

41. SHARSHAR, TAREK ; BOZZA, FERNANDO ; CHRÉTIEN, FABRICE . Neuropathological processes in sepsis. Lancet Neurology

(Print), v. 13, p. 534-536, 2014. http://dx.doi.org/10.1016/S1474-4422(14)70064-X

178


178

42. SILVA, JOHNATAS D. ; PAREDES, BRUNO D. ; ARAÚJO, INDIANARA M. ; LOPES-PACHECO, MIQUÉIAS ; OLIVEIRA,

MILENA V. ; SUHETT, GRAZIELLE D. ; FACCIOLI, LANUZA A. P. ; ASSIS, EDSON ; CASTRO-FARIA-NETO, HUGO C. ;

GOLDENBERG, REGINA C. S. ; CAPELOZZI, VERA L. ; MORALES, MARCELO M. ; PELOSI, PAOLO ; XISTO, DÉBORA G. ;

ROCCO, PATRICIA R. M. . Effects of Bone Marrow-Derived Mononuclear Cells From Healthy or Acute Respiratory Distress Syndrome

Donors on Recipient Lung-Injured Mice. Critical Care Medicine, v. 42, p. 1, 2014. http://dx.doi.org/10.1097/ccm.0000000000000296

43. SILVA, VANESSA R. ; MARCONDES, P. ; SILVA, M. ; VILLAVERDE, ANTONIO B. ; CASTRO-FARIA-NETO, HUGO C. ;

VIEIRA, RODOLFO P. ; AIMBIRE, FLAVIO ; DE OLIVEIRA, ANA PAULA L. . Low-level laser therapy inhibits bronchoconstriction,

Th2 inflammation and airway remodeling in allergic asthma. Respiratory Physiology & Neurobiology, v. 14, p. S1569-9048(14), 2014.


44. SOUZA RODRIGUES, ROSANA; MENNA BARRETO, MIRIAM ; MARCHIORI, EDSON . Varices pericárdicas secundarias a

mediastinitis fibrosante. Archivos de Bronconeumología (Ed. impresa), v. 1, p. 1-2, 2014. http://dx.doi.org/10.1016/j.arbres.2014.03.004

45. STIEBLER, RENATA ; MAJEROWICZ, D. ; KNUDSEN, J. ; GONDIM, K. C. ; WRIGHT D.W. ; EGAN, TIMOTHY J. ; OLIVEIRA

M.F. . Unsaturated Glycerophospholipids Mediate Heme Crystallization: Biological Implications for Hemozoin Formation in the Kissing

Bug Rhodnius prolixus. Plos One, v. 9, p. e88976, 2014. http://dx.doi.org/10.1371/journal.pone.0088976


1. ALMEIDA, PATRÍCIA E. ; ROQUE, NATÁLIA R. ; MAGALHÃES, KELLY G. ; MATTOS, KATHERINE A. ; TEIXEIRA, LIVIA ;

MAYA-MONTEIRO, CLARISSA ; ALMEIDA, CECÍLIA J. ; CASTRO-FARIA-NETO, HUGO C. ; RYFFEL, BERNHARD ;

QUESNIAUX, VALÉRIE F.J. ; BOZZA, PATRÍCIA T. . Differential TLR2 downstream signaling regulates lipid metabolism and

cytokine production triggered by Mycobacterium bovis BCG infection. Biochimica and Biophysica Acta. Molecular and Cell Biology of

Lipids, v. 1841, p. 1841(1):97-107, 2013. http://dx.doi.org/10.1016/j.bbalip.2013.10.008

2. AMANCIO, RODRIGO T. ; JAPIASSU, ANDRE M. ; GOMES, RACHEL N. ; MESQUITA, EMERSOM C. ; ASSIS, EDSON F. ;

MEDEIROS, DENISE M. ; GRINSZTEJN, BEATRIZ ; BOZZA, PATRÍCIA T. ; CASTRO-FARIA, HUGO C. ; BOZZA, FERNANDO

A. . The Innate Immune Response in HIV/AIDS Septic Shock Patients: A Comparative Study. Plos One, v. 8, p. e68730, 2013.


3. AMORIM, V. B. ; RODRIGUES, R. S. ; BARRETO MM ; ZANETTI, G. ; HOCHHEGGER B ; MARCHIORI, E. . Influenza A (H1N1)

pneumonia: HRCT findings. Jornal Brasileiro de Pneumologia (Impresso), v. 39, p. 323-329, 2013. http://dx.doi.org/10.1590/S0100-

39842013000500006

4. AMORIM, V. B. ; RODRIGUES, R. S. ; BARRETO, M. M. ; ZANETTI, GLÁUCIA ; MARCHIORI, E ; MARCHIORI, EDSON .

Computed tomography findings in patients with H1N1 influenza A infection. RB. Radiologia Brasileira (Impresso), v. 46, p. 299-306,

2013.

5. BARRETO, MIRIAM MENNA ; RAFFUL, PATRICIA PIAZZA ; RODRIGUES, ROSANA SOUZA ; ZANETTI, GLÁUCIA ;

HOCHHEGGER, BRUNO ; SOUZA, ARTHUR SOARES ; GUIMARÃES, MARCOS DUARTE ; MARCHIORI, EDSON . Correlation

between computed tomographic and magnetic resonance imaging findings of parenchymal lung diseases. European Journal of Radiology,

v. 82, p. 492-501, 2013. http://dx.doi.org/10.1016/j.ejrad.2013.04.037

6. BOZZA, FERNANDO A.; D?AVILA, JOANA C. ; RITTER, CRISTIANE ; SONNEVILLE, ROMAIN ; SHARSHAR, TAREK ; DAL-

PIZZOL, FELIPE . Bioenergetics, Mitochondrial Dysfunction, and Oxidative Stress in the Pathophysiology of Septic Encephalopathy.

Shock (Augusta, Ga.), v. 39, p. 10-16, 2013. http://dx.doi.org/10.1097/shk.0b013e31828fade1

7. CARVALHO, A.R. ; BERGAMINI, B.C. ; CARVALHO, N.S. ; CAGIDO, V.R. ; JARDIM-NETO, A.C. ; JANDRE, F.C. ; ZIN, W. A. ;

GIANNELLA NETO, A. . Volume-independent elastance: A useful parameter for the open-lung positive end-endexpiratory pressure

adjustment. Anesthesia and Analgesia, v. 116, p. 627-633, 2013. http://dx.doi.org/10.1213/ANE.0b013e31824a95ca

8. CARVALHO, ALYSSON RONCALLY. Simple Tool for Bedside Stratification. Critical Care Medicine, v. 41, p. 912-913, 2013.

9. CARVALHO, VINICIUS ; FERNANDES, LOHENGRIN ; CONDE, TALINE ; ZAMITH, HELENA ; SILVA, RONALD ; SURRAGE,

ANDREA ; FRUTUOSO, VALBER ; CASTRO-FARIA-NETO, HUGO ; AMENDOEIRA, FABIO . Antinociceptive Activity of

Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation. Marine Drugs, v. 11, p. 1221, 2013.

http://dx.doi.org/10.3390/md11041221

10. CHAVES, E ; FORTUNATO, R. ; CARVALHO, D. P. ; NASCIMENTO, J. H. ; OLIVEIRA M.F. . Exercise-induced cardioprotection is

impaired by anabolic steroid treatment through a redox-dependent mechanism. Journal of Steroid Biochemistry and Molecular Biology, v.

86, p. 21-29, 2013. http://dx.doi.org/10.1016/j.jsbmb.2013.06.006

11. D'AVILA, J ; RODRIGUES, R ; CASTRO-FARIA-NETO, H ; OLIVEIRA, M ; BOZZA, F . Bioenergetic imbalance and oxidative stress

in the pathophysiology of septic encephalopathy. Critical Care (London. Print), v. 17, p. P22, 2013. http://dx.doi.org/10.1186/cc11960

12. DE LIMA, FLÁVIA MAFRA ; ALBERTINI, REGIANE ; DANTAS, YVANA ; MAIA-FILHO, ANTONIO LUIS ; DE LOURA

SANTANA, CRISTIANO ; CASTRO-FARIA-NETO, HUGO CAIRE ; FRANÇA, CRISTIANE ; VILLAVERDE, ANTONIO BALBIN ;

AIMBIRE, FLÁVIO . Low-Level Laser Therapy Restores the Oxidative Stress Balance in Acute Lung Injury Induced by Gut Ischemia

and Reperfusion. Photochemistry and Photobiology, v. 89, p. 179-188, 2013. http://dx.doi.org/10.1111/j.1751-1097.2012.01214.x

13. FLOYD, ROBERT A. ; CASTRO FARIA NETO, HUGO C. ; ZIMMERMAN, GUY A. ; HENSLEY, KENNETH ; TOWNER, RHEAL

A. . Nitrone-based Therapeutics for Neurodegenerative Diseases. Their use alone or in Combination with Lanthionines. Free Radical

Biology & Medicine, v. 1, p. S0891-5849(13, 2013. http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.033

14. GOMES, RACHEL N. ; TEIXEIRA-CUNHA, MARIANA G. A. ; FIGUEIREDO, RODRIGO T. ; ALMEIDA, PATRICIA E. ; ALVES,

SILVIO C. ; BOZZA, PATRÍCIA T. ; BOZZA, FERNANDO A. ; BOZZA, MARCELO T. ; ZIMMERMAN, GUY A. ; CASTRO-

FARIA-NETO, HUGO C. . Bacterial Clearance in Septic Mice is Modulated by MCP-1/CCL2 and Nitric Oxide. Shock (Augusta, Ga.), v.

1, p. 1-69, 2013. http://dx.doi.org/10.1097/shk.0b013e31827802b5

15. GONÇALVES-DE-ALBUQUERQUE, CASSIANO FELIPPE ; BURTH, PATRÍCIA ; SILVA, ADRIANA RIBEIRO ; DE MORAES,

ISABEL MATOS ; DE JESUS OLIVEIRA, FLORA MAGNO ; SANTELLI, RICARDO ERTHAL ; FREIRE, ALINE SOARES ;

BOZZA, PATRÍCIA TORRES ; YOUNES-IBRAHIM, MAURICIO ; DE CASTRO-FARIA-NETO, HUGO CAIRE ; DE CASTRO-

FARIA, MAURO VELHO . Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and

eicosanoid production. Journal of Inflammation (London. Online), v. 10, p. 34, 2013. http://dx.doi.org/10.1186/1476-9255-10-34

16. HOCHHEGGER, B. ; IRION, K. ; HOCHHEGGER, D. R. ; RODRIGUES, R. ; SARTORI, A. ; Marchiori, E. ; ZUO, Y.-Z. ; LIU, S.-W. .

Anterior Segment and Medial Segment of the Left Lower Lobe: A New and Unknown Nomenclature. Radiology, v. 269, p. 310-311,

2013. http://dx.doi.org/10.1148/radiol.13130771

17. HOCHHEGGER, B. ; Marchiori, E. ; SOUZA, L. SOARES ; RAFFUL, P. ; RODRIGUES, R. . Magnetic resonance in N staging of lung

cancer. European Journal of Radiology, v. 82, p. 193, 2013. http://dx.doi.org/10.1016/j.ejrad.2012.01.014

18. HOTTZ, E. D. ; LOPES, J. F. ; FREITAS, C. ; VALLS-DE-SOUZA, R. ; OLIVEIRA, M. F. ; BOZZA, M. T. ; DA POIAN, A. T. ;

WEYRICH, A. S. ; ZIMMERMAN, G. A. ; BOZZA, F. A. ; BOZZA, P. T. . Platelets mediate increased endothelium permeability in

dengue through NLRP3-inflammasome activation. Blood (Philadelphia, PA), v. 122, p. 3405-3414, 2013. http://dx.doi.org/10.1182/blood-

2013-05-504449

19. HOTTZ, E. D. ; OLIVEIRA, M. F. ; NUNES, P. C. G. ; NOGUEIRA, R. M. R. ; VALLS-DE-SOUZA, R. ; DA POIAN, A. T. ;

WEYRICH, A. S. ; ZIMMERMAN, G. A. ; BOZZA, P. T. ; BOZZA, F. A. . Dengue induces platelet activation, mitochondrial

dysfunction and cell death through mechanisms that involve DC-SIGN and caspases. Journal of Thrombosis and Haemostasis (Print), v.

11, p. 951-962, 2013. http://dx.doi.org/10.1111/jth.12178

20. MARCHIORI, E ; ZANETTI, G ; RODRIGUES, ROSANA SOUZA ; HOCHHEGGER B . Pulmonary Arterial Aneurysms. American

Journal of Respiratory and Critical Care Medicine, v. 187, p. 212-212, 2013. http://dx.doi.org/10.1164/rccm.201209-1652IM

21. MARCHIORI, E. ; RODRIGUES, R. S. ; REIS, M. C. M. ; ZANETTI, G. ; MENNA BARRETO, M. . Pleural nodules in a patient with a

colonic tumour. Thorax, v. 69, p. 395-395, 2013. http://dx.doi.org/10.1136/thoraxjnl-2013-204727

22. MARON-GUTIERREZ, TATIANA ; SILVA, JOHNATAS ; CRUZ, FERNANDA ; ALEGRIA, SAMANTHA ; XISTO, DEBORA ;

ASSIS, EDSON ; CASTRO-FARIA-NETO, HUGO ; SANTOS, CLAUDIA CHIMISSO ; MORALES, MARCELO ; ROCCO,

179


179

PATRICIA RIEKEN . Insult-dependent effect of bone marrow cell therapy on inflammatory response in a murine model of

extrapulmonary acute respiratory distress syndrome. Stem cell research & therapy, v. 4, p. 123, 2013. http://dx.doi.org/10.1186/scrt334

23. MELO, A. C. ; VALENCA, S. S. ; GITIRANA, L. B. ; SANTOS, J. C. ; RIBEIRO, M. L. ; MACHADO, M. N. ; MAGALHAES, C. B. ;

ZIN, W. A. ; PORTO, L. C. . Redox markers and inflammation are differentially affected by atorvastatin, pravastatin or simvastatin

administered before endotoxin-induced acute lung injury. International Immunopharmacology (Print), v. 17, p. 57-64, 2013.

http://dx.doi.org/10.1016/j.intimp.2013.05.016

24. NORMANDO, V.M.F. ; MAZZOLI-ROCHA, F. ; MOREIRA, D.K.M. ; BARCELLOS, B.C. ; PICANÇO-DINIZ, D.L.W. ; ZIN, W. A. .

Regular exercise training attenuates pulmonary inflammatory responses to inhaled alumina refinery dust in mice. Respiratory Physiology

& Neurobiology, v. 186, p. 53-60, 2013. http://dx.doi.org/10.1016/j.resp.2012.12.010

25. PESCE LAMAS CONSTANTINO, CAROLINA ; SOUZA RODRIGUES, ROSANA ; ARAUJO OLIVEIRA NETO, JAIME ;

MARCHIORI, EDSON ; EIRAS ARAUJO, ANTONIO LUIS ; RENATA DE MELLO PEREZ, NULL ; BRAZ PARENTE, DANIELLA

. Computed Tomography and Magnetic Resonance Enterography Findings in Crohn?s Disease: What Does the Clinician Need to Know

From the Radiologist?. Canadian Association of Radiologists Journal, v. 65, p. 42, 2013. http://dx.doi.org/10.1016/j.carj.2012.11.004

26. SANTOS, RAQUEL SOUZA ; SILVA, PEDRO LEME ; OLIVEIRA, GISELE PENA DE ; SANTOS, CINTIA LOURENÇO ; CRUZ,

FERNANDA FERREIRA ; ASSIS, EDSON FERNANDES DE ; CASTRO-FARIA-NETO, HUGO CAIRE DE ; CAPELOZZI, VERA

LUIZA ; MORALES, MARCELO MARCOS ; PELOSI, PAOLO ; GATTASS, CERLI ROCHA ; ROCCO, PATRICIA RIEKEN

MACEDO . Oleanolic acid improves pulmonary morphofunctional parameters, in experimental sepsis by modulating oxidative and

apoptotic processes. Respiratory Physiology & Neurobiology, v. 31, p. 10(1):34, 2013. http://dx.doi.org/10.1016/j.resp.2013.08.019

27. TEIXEIRA-DA-CUNHA, MARIANA G. A. ; GOMES, RACHEL N. ; ROEHRS, NATHASSIA ; BOZZA, FERNANDO A. ;

PRESCOTT, STEPHEN M. ; STAFFORINI, DIANA ; ZIMMERMAN, GUY A. ; BOZZA, PATRICIA T. ; CASTRO-FARIA-NETO,

HUGO C. . Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration.


28. TOWNER, RHEAL A. ; GARTEISER, PHILIPPE ; BOZZA, FERNANDO ; SMITH, NATALIYA ; SAUNDERS, DEBRA ; D'AVILA,

JOANA C.P. ; MAGNO, FLORA ; OLIVEIRA, MARCUS F. ; EHRENSHAFT, MARILYN ; LUPU, FLOREA ; SILASI-MANSAT,

ROBERT ; RAMIREZ, DARIO C. ; GOMEZ-MEJIBA, SANDRA E. ; MASON, RONALD P. ; FARIA-NETO, HUGO C CASTRO . In

Vivo Detection of Free Radicals in Mouse Septic Encephalopathy using Molecular MRI and Immuno-Spin-Trapping. Free Radical

Biology & Medicine, v. 23, p. 65C:828-837, 2013. http://dx.doi.org/10.1016/j.freeradbiomed.2013.08.172

29. WALTER-NUNO AB ; OLIVEIRA MP ; OLIVEIRA, M. F. ; GONÇALVES RLS ; RAMOS IB ; KOERICH LB ; OLIVEIRA, P.L. ;

PAIVA-SILVA, GABRIELA O. . Silencing of maternal Heme Binding Protein causes embryonic mitochondrial dysfunction and impairs

embryogenesis in the blood sucking insect Rhodnius prolixus. The Journal of Biological Chemistry (Print), v. 111, p. 111-120, 2013.


30. YOSHIDA, TAKESHI ; TORSANI, VINICIUS ; GOMES, SUSIMEIRE ; SANTIAGO, ROBERTA R.S. ; BERALDO, MARCELO ;

TUCCI, MAURO R. ; ZIN, WALTER A. ; KAVANAGH, BRIAN P. ; AMATO, MARCELO B. P. . Spontaneous Effort Causes Occult

Pendelluft during Mechanical Ventilation. American Journal of Respiratory and Critical Care Medicine, v. 188, p. 1420-1427, 2013.

http://dx.doi.org/10.1164/rccm.201303-0539oc

180


180

Scientific meetings and training of human resources

181


181

INBEB Conferences and Meetings

The events organized by the Institute allows our Associate Laboratories to present their

work to other members, as well as to external researchers. In such instances, INBEB groups

enjoy opportunity of further interaction, which helps them to improve their work and establish

new partnerships.

National Meeting of microPET/SPECT/CT users.

October – 2015

Promoted by Cenabio and IDOR, the Seminar was held in partnership between Cenabio

II and IDOr, in Rio de Janeiro. It featured lectures around the topics involved in the use of the

device as well as ongoing projects. Some of the topics covered concerned the production of new

radiopharmaceuticals; Several types of phantoms available for studies of tomography, Nuclear

Medicine, and Magnetic Resonance; Image processing in preclinical studies; Benefits of

fluoridated choline in clinical practice in the diagnosis of prostate cancer; Research with

laboratory animals using microPET; And others.

Invited key-note speakers

182


182

5th INBEB Conference

May - 2014

The 5th INBEB Annual Seminar took place on May 7, 8 and 9, 2014, in the Health

Sciences Center (CCS) of the Federal University of Rio de Janeiro (UFRJ), Campus Fundão.

The event included lectures by representatives of the various Associated Laboratories of

INBEB, as well as the inauguration of new facilities at the National Nuclear Magnetic

Resonance Center Jiri Jonas (CNRMN / CENABIO).

Also, a tutorial on the determination of membrane protein structure by solid state NMR

was offered. The free workshop was ministered by researcher Barth-Jan van Rossum (Leibniz

für Molekulare Pharmakologie, Berlin, Germany).

The best posters were awarded with funds for participation in national and international

academic events.

Symposium on Non-thermal Food Technologies

November - 2013

On November 4, 2013, INBEB promoted the Mini Symposium: "international

cooperation on non-thermal technologies in foods".

The event promoted institutional presentations on general information, infrastructure,

projects and actions in non-thermal technologies. In addition, the event included presentations

on examples of international cooperation, including the cases of FAPERJ; Embrapa / Labex;

European Union; CNPq; CAPES and IFT.

Several institutions participated in the symposium, such as:

1) Embrapa Agroindústria de Alimentos;

2) UFRJ / INBEB;

3) UFRJ / IQ (Food Science);

4) University of Padova;

5) CSIRO / Australia;

6) University of Bio-Bio / Chile;

7) INTA / Argentina;

8) CSIC / Spain;

9) ATB - Leibniz Institute for Agricultural Engineering;

10) Cornell University;

11) Mutilvac;

12) Senai;

13) US Army Natick Research Center.

The event was held at the Helio Fraga Auditorium, in the Health Sciences building at

Federal University of Rio de Janeiro, Campus Fundão.

183


183

4th INBEB Conference

May - 2013

The Fourth Annual Meeting of INBEB occurred on 8, 9 and 10 of May, 2013, in the

Professor Hélio Fraga Auditorium, at the Federal University of Rio de Janeiro. The event also

presented the scientific results of the 20 Associate Laboratories from INBEB, including various

lectures and about 200 posters.

This meeting was This meeting was attended by the Swiss researcher Kurt Wüthrich,

Nobel Prize winner for chemistry in 2002. During the event, it was inaugurated a room-office

for Wüthrich at the INBEB headquarters. The Nobel Prize winner also presented the main

conference: "Historical Development and Current Trends of NMR in Structural Biology and

Biotechnology".

Wüthrich maintains a partnership with the Institute through the federal program Science

Without Borders, and has served as a visiting professor at INBEB / UFRJ since July 2012,

which guides the work of doctoral and post-doctoral.

Professor wüthrich at the conference and at his INBEB’s office.

184


184

Other events supported by INBEB

The Institute also supported or helped in several fashions events that represent a

contribution to the progress of science. Some of them are listed below:

Lecture at the SBQ Annual Meeting

June 2016

Due to an invitation of the Brazilian Chemical Society (SBQ), the INBEB associate

researcher, Kurt Wüthrich, Nobel Prize for Chemistry in 2002, traveled to the city of Goiânia, in

the Brazilian Midwest, to deliver a keynote speak in its 39th Annual meeting. The lecture was

about the current status of Nuclear Magnetic Resonance and the fruits of two decades of basic

research. Wültrich recalled discovery and evolution of the technique, paying tribute to those

who paved the scientific way to his Nobel Prize. After the lecture, the guests were able to enjoy

an informal talk with the researcher, who talked about chemistry, science and his passion for

sports.

Kurt Wültrich at the 39th Brazilian Chemistry Society Conference. Pictures by

Marcus de Melo (from the official conference divulgation).

INBEB and IDOR support event on protein folding in neurodegenerative diseases

and cancer

August - 2015

The symposium "Frontiers in Protein Misfolding in Neurodegenerative Diseases and

Cancer" took place at IDOR headquarters. It was a parallel event to the 23rd International Congress

of the International Union of Biochemistry and Molecular Biology (IUBMB) and the 44th Annual

Meeting of the Society Brazilian University of Biochemistry and Molecular Biology (SBBq).

185


185

Among the invited speakers, there were several INBEB members, such as the Nobel Prize-winning

researcher Kurt Wutrich and coordinator Jerson Lima da Silva.

Poster of the event (top left) / The researcher Kurt Wültrich (top right) / Event

organizers and invited speakers (bottom photo).

186


186

International Event on Biopolymers in Rio de Janeiro

July - 2015

The Biophysical Society's thematic seminar "Polymers and Self-Assembly: From Biology to

Nanomaterials" was held in Rio de Janeiro from October 25 to 30, 2015, at the Brazilian Center for

Physical Research.

Many proteins are arranged in the form of polymers. This can result in natural arrangements

(such as actin and tubulin) and also in abnormal and pathological forms (such as amyloid protein,

which accumulates in organs and tissues, causing the disease amyloidosis). Therefore, the study of

the structure and function of these biological polymers is an important field of research for

biophysics, bringing together chemists, chemical engineers, physicists, and material scientists.

The seminar brought together the different multidisciplinary areas to share techniques and

innovations in the area of biopolymers, enhancing the knowledge of these complex systems. It

featured lectures from 25 prominent scientists in nine countries: Germany, Argentina, Australia,

China, the United States, France, the United Kingdom, Singapore, and Brazil.

INBEB on iPoLS

July - 2014

INBEBs Researchers represent Brazil at the Annual Conference of the International Physics

of Living Systems (iPoLS) Network, which took place from July 21 to 24 in Munich, Germany. The

trans-institutional program promotes the interaction of pioneer groups in the use of theoretical and

experimental physics to promote understanding of biology and biomedicine.

Researchers Jerson Lima da Silva, Fernanda Tovar Moll and Monica Santos de Freitas,

from the Federal University of Rio de Janeiro and members of INBEB, are among the invited

speakers. The event also had representatives from CNRS (France); Georgia Institute of Technology;

Harvard University; LMU Munich; Max Planck Institute of Biochemistry; National University of

Singapore; Princeton University; Rice University; University of Illinois at Urbana-Campaign;

University of Maryland; Tel Aviv University; TU Munich; Weizmann Institute of Science and Yale

University.

Brazil-Canada Workshop on Prion Studies

March 2014

The workshop was held on March 17 and 18, 2014. As a result of a Brazil-Canada

cooperation, the event promoted discussions on advances of science on the study of prions and

especially on diseases caused by improper coiling of prion-like proteins. The event was held in

Banff, Alberta, Canada.

Sponsored by the Alberta Prion Research Institute, Fapesp and Faperj, the event hosted

the encounter of 25 Brazilian and Canadian researchers to discuss serious scientific and

socioeconomic challenges in the two countries. Among the Brazilian speakers are the INBEB

researchers, Prof. Jerson Lima Silva (UFRJ), Prof. Débora Foguel (UFRJ), Prof. Yraima

187


187

Cordeiro (UFRJ), Prof. Carlos Ramos (Unicamp), Dr. Jerusa Smid (USP), and Dr.Tuane Vieira

(UFRJ).

Invited speakers at the event venue.

Magna Meeting of the Brazilian Academy of Sciences (ABC)

May - 2013

On May 6, 7 and 8, 2013, the ABC Magna Meeting brought a Fields Medal winner and

3 Nobel Prize winners - among them Kurt Wüthrich, a visiting researcher at INBEB.

The meeting was originally intended to be a time of fellowship between the

Academicians, the celebration of the incorporation of new scientists to the Academy and

reception of various authorities related to Science, Technology and Innovation.

In recent years, it also became an occasion for comprehensive and multidisciplinary

debates, combining lectures from senior researchers with presentations from outstanding young

researchers in the various areas of science.

In order to contribute to the country’s reach of new levels in its scientific and

technological development, some priority topics were discussed at the ABC Magna Meeting.

They were: major projects promoted through scientific policies, improvement of science

teaching and higher education structure, stimulation of research and development in companies

and investment in science, technology and innovation in health.

In addition to publicizing the main ongoing efforts in behalf of scientific development,

the meeting proposed complementary measures that, in the view of the scientific community,

can enhance such efforts, for the benefit of society.

188


188

Poster of the event

Regular seminars

The Institute promotes regular seminars at the Federal University of Rio de Janeiro. In

the quadrennium, 25 lectures were organized, as listed below:

• 05/07/2013

Aline Faro (Instituto de Física/São Carlos/USP):

"Proteínas fluorescentes e o mecanismo de foto comutação reversível".

• 12/07/2013

Etel R. P. Gimba (Profa. Adjunta do Polo Universitário de Rio das Ostras/UFF e

Pesquisador visitante sênior no INCA):

"Investigação funcional de genes envolvidos na progressão tumoral como estratégia na

descrição de biomarcadores e alvos terapêuticos".

• 22/10/2013

Elio Cino (Pesquisador visitante do INBEB):

189


189

"Conformational biases of linear motifs".

• 06/12/2013

Maria Isabel Achatz (Cientista assistente da Fundação Antônio Prudente/Hospital A. C.

Camargo):

"TP53 e a síndrome de Li-Fraumeni: o desafio do diagnóstico de famílias de alto risco".

• 24/01/2014

Lucia Banci (Professora de Química/Diretora do CERM (Centro

di Ricerca di Risonanze Magnetiche)/Universidade de Florença/Itália):

"From single proteins to cellular functions: the unique contribution of NMR".

• 20/02/2014

Gonzalo de Prat Gay (Protein Structure-Function and Engineering Laboratory,

Fundación Instituto Leloir and IIBBA-CONICET, Buenos Aires, Argentina):

“Análise bioquímica e biofísica de proteínas do vírus sincicial respiratório humano:

Fosfoproteína P, proteína anti-terminadora da transcrição M2-1, e proteína não estrutural NS1".

• 24/03/2014

Sergio Marco (Directeur de Recherche INSERM):

"Theory and practice in 3D electron microscopy and chemical mapping for biology."

• 31/03/2014

Christian Roumestand (Centre de Biochimie Structurale/Montpellier):

“Mycobacterium tuberculosis Virulence Factors: Ressuscitation mechanism, STPK

signalisation, membrane permeability".

• 07/05/2014

Kurt Wüthrich (The Scripps Research Institute/Eidgenössische Technische Hochschule

Zürich/Prof. Visitante do IBqM/UFRJ/INBEB):

“A Personal View of the History of NMR in Structural Biology and Medical

Diagnosis”.

• 07/05/2014

Barth-Jan van Rossum (Leibniz Institute für Molekulare Pharmakologie, Berlin,

Germany):

“Determinação de estrutura de proteínas de membrana por Ressonância Magnética

Nuclear em estado sólido”.

190


190

• 27/05/2014

Luis Serrano Pubul (ICREA Professor/CRG Director):

"Erb-MPAK pathway and the role of protein concentration in signaling”.

• 06/06/2014

Suparna Sanyal (Uppsala University):

“Protein folding activity of the ribosome (PFAR) and prion diseases".

• 31/07/2014

Patrícia Souza dos Santos (INBEB/UFRJ):

"Os Cursos de Férias: o amor e a inspiração pra uma vida!".

• 15/09/2014

Matilde Bongianni (University of Verona/It):

"RT-QuIC of olfactory neuroepithelium brushings as an intravital diagnosis for

Creutzfeldt-Jakob disease."

• 30/09/2014

Fabio Almeida (CNRMN/INBEB/UFRJ):

“RMN para estrutura e dinâmica de proteínas e metabolômica”.

• 08/10/2014

Sergio Souza (INBEB/UFRJ):

“PET/SPECT/CT – Aplicações pré-clínicas”

• 14/10/2014

Emiliano Medei (INBEB/IBCCF/UFRJ):

“IVIS-Xenogen: visão atual e perspectivas no CENABIO”.

• 21/10/2014

Fernanda Tovar Moll (I’DOR/INBEB/UFRJ):

“Bioimagem translacional – aplicações da Imagem por Ressonância Magnética”.

• 29/10/2014

Kildare Miranda (INBEB/UFRJ):

“Microscopia Eletrônica 3D”.

191


191

• 04/11/2014

Adriana Bastos Carvalho (INBEB/UFRJ):

“Ultrassonografia - FACS”.

• 05/11/2014

Luminita Paraoan (University of Liverpool):

“Milestones of intracellular trafficking of cystatin C in the retinal pigment epithelium:

re-routing toward age-related macular degeneration”.

• 18/08/2015

Enrico Gratton (Laboratory for Fluorescence Dynamics/University of California):

"Mechanisms of molecular transport through nuclear pore complexes in live cells."

• 07/10/2015

Jeffrey Lengyel ( FEI Company, Hillsboro/USA):

“Cryo-TEM: A new era for 3D structural analysys of protein complexes”.

• 16/10/2015

Jack Johnson (Scripps Research Institute in La Jolla/California):

"Virus Particle Maturation: An Experimental Laboratory for the Study of

Macromolecular Dynamics".

• 24/11/2015

Tiago Fleming Outeiro (Department of Neuro Degeneration and Restorative Research

Center for Nanoscale Microscopy and Molecular Physiology of the Brain/University Medical

Center/ Goettingen/Germany):

"From the bench to the bedside: deciphering the molecular basis of Parkinson's

disease".

192


192

Training and teaching human resources

The INBEB members are integrated into graduate programs, several of which were given

a grade of 6 or 7 by the CAPES evaluation. The training of students is crucial to produce high-

quality science with publications in high-impact journals. We believe that the following

comments, which we have received from Professor Edilene Oliveira da Silva (coordinator of AL

14 – ICB/UFPA), summarizes much of INBEB's success in encouraging the improvement of

students from disadvantaged regions:

“Considering the geographic and scientific isolation of the LA 14, INBEB's support

favored a technical-scientific advance, representing a qualitative and quantitative leap in

personnel training and publications in journals of international circulation. In addition, it

favored an expressive participation of the LA 14 members in activities of education and

dissemination of science in the basic education of students from poor municipalities of the

Amazon region.”

In fact, in the period, INBEB financed four travels of UFPA students to Rio de Janeiro to

learn new research techniques:

- From July 15th to 26th of 2013, the Master student Bruno Jose Martins da Silva traveled

to the State University Center of West Zone from Rio de Janeiro. The student has developed its

activities in laboratory technology in biochemistry and microscopy, performed a research

related to the development of new drugs against leishmaniasis.

- From March 12 thto 21th of 2015, Bruno Jose Martins da Silva now traveled as a Ph.D.

student to the Federal University of Rio de Janeiro. At the Laboratory of ultrastructure cell

Hertha Meyer,the student learned the cryo-ultramicrotomy technique and performed analysis on

the transmission electron microscope.

- Also, in july 2013, the Masters students Caroline Martins Almeida and Paula Cristina

Rodrigues Frade went to the Federal University of Rio de Janeiro, at the AL2, Associate

Laboratory of Structural Biology of cardiac and Amyloidogenic proteins, coordenate by Debora

Foguel, to learn new techniques (such as immunoblotting), perform experiments and to keep a

closer collaboration.

Furthermore, during the period from 2013 to 2016, our groups have guided hundreds of

graduate students, obtaining the equivalent of:

- 184 master’s dissertations (22 in 2016; 56 in 2015; 6 in 2014 and 46 in 2013);

- 176 Doctoral thesis (34 in 2016; 42 in 2015; 52 in 2014 and 48 in 2013).

We present the listing of each of these students and their respective laboratories as follows:

193


193

- Doctoral thesis completed:

AL 1 - Associated Laboratory of Virus and Cancer Structural Biology

(Coordinator: Jerson Lima da Silva - Instituto de Bioquímica Médica - IBqM/UFRJ)

Total of 11 Doctoral thesis completed during the whole period, as follows:

2016:

1. Bruno Macedo da Silva. Estudos in vitro e in vivo de conversão e agregação da proteína

prion: efeito de ácidos nucleicos e a proposta de um modelo de agregação amiloide. 2016.

Doctoral thesis (Doutorado em Ciências Farmacêuticas) - Universidade Federal do Rio de

Janeiro, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do RJ. Advisor:

Yraima Moura Lopes Cordeiro.

2. Carlos Henrique Dumard. Vírus da influenza inativado por pressão hidrostática: uma

perspectiva de vacina universal?. 2016. Doctoral thesis (Doutorado em Química

Biológica) - Universidade Federal do Rio de Janeiro, Coordenação de Aperfeiçoamento

de Pessoal de Nível Superior. Advisor: Jerson Lima da Silva.

3. Cláudia M.N. Drummond Fonseca. PERFIL DA NARRATIVA DE INDIVÍDUOS COM

COMPROMETIMENTO COGNITIVO LEVE: CORRELAÇÃO COM BASES

NEURAIS DA LINGUAGEM. 2016. Doctoral thesis (Doutorado em Ciências

Morfológicas) - Universidade Federal do Rio de Janeiro, . Advisor: Fernanda Freire

Tovar Moll.

4. Gabriel Coutinho. Correlação de perfis neuropsicológico e de neuroimagem como fator

de risco de progressão de Comprometimento Cognitivo Leve para Doença de Alzheimer.

2016. Doctoral thesis (Doutorado em Ciências Morfológicas) - Universidade Federal do

Rio de Janeiro, . Advisor: Fernanda Freire Tovar Moll.

5. Myriam de Carvalho Monteiro. NEUROPLASTICIDADE NA DISGENESIA DO

CORPO CALOSO: ASPECTOS ANATÔMICOS, FUNCIONAIS E

NEUROPSICOLÓGICOS. 2016. Doctoral thesis (Doutorado em Programa de Ciências

Morfológicas (PCM)- Universidade Federal do Rio de Jan) - Universidade Federal do Rio

de Janeiro, . Advisor: Fernanda Freire Tovar Moll.

6. Rodrigo Jorge Vianna Barbosa. PLASTICIDADE DE LONGA DISTANCIA EM

MODELOS ANIMAIS DE DISGENESIA CALOSA.. 2016. Doctoral thesis (Doutorado

em Ciências Morfológicas) - Universidade Federal do Rio de Janeiro, Conselho Nacional

de Desenvolvimento Científico e Tecnológico. Advisor: Fernanda Freire Tovar Moll.

2015:

1. Natália do Carmo Ferreira. IDENTIFICAÇÃO DE NOVOS CANDIDATOS A

FÁRMACOS ANTI-PRION ATRAVÉS DE METODOLOGIAS IN VITRO E IN

SILICO. 2015. Doctoral thesis (Doutorado em Ciências Farmacêuticas) - Universidade

Federal do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível

Superior. Advisor: Yraima Moura Lopes Cordeiro.

2014:

1. Gilson Costa dos Santos Junior Estudo da cromatina nos sitios de fixação à matriz nuclear

no dominio do gene TP53 e das modificações epigenéticas no meodelo de progressão

tumoral mamaria 21T. 2014. , Conselho Nacional de Desenvolvimento Científico e

Tecnológico. Advisor Cláudia Vitória de Moura Gallo.

2013:

1. Aline da Rocha Matos. Caracterização da expressão e função da trombospondina 2 no

câncer de próstata. 2013. Doctoral thesis (Doutorado em Pós Graduação Stricto Sernsu

em Oncologia) - Instituto Nacional de Câncer, Ministério da Sáude. Advisor: Etel

Rodrigues Pereira Gimba.

2. Guilherme Augusto Piedade de Oliveira. Aplicações em Biologia Estrutural para a

Compreensão de Sistemas Biológicos. 2013. Doctoral thesis (Doutorado em Química

Biológica) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Jerson Lima da Silva.

194


194

3. Karen Medeiros Gonçalves. RELAÇÃO ESTRUTURA-ATIVIDADE DE LIPASES

COMERCIAIS LIVRES E EM MICELAS REVERSAS. 2013. Doctoral thesis

(Doutorado em Ciências Farmacêuticas) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint supervisor: Yraima

Moura Lopes Cordeiro.


Proteins

(Coordinator: Débora Foguel- Instituto de Bioquímica Médica - IBqM/UFRJ)


2015:

1. Estefania Pereira Cardoso Azevedo. Papel da imunidade inata no desenvolvimento e pro-

gressão das amiloidoses. 2015. Doctoral thesis (Doutorado em Química Biológica) -

Universidade Federal do Rio de Janeiro, Fundação Carlos Chagas Filho de Amparo à

Pesquisa do Estado do RJ. Advisor: Debora Foguel.

2014:

1. Cícero Figueiredo-Freitas. S-nitrosilação de proteínas sarcoméricas: Novos alvos para

modulação da contratilidade cardíaca.. 2014. Doctoral thesis (Doutorado em Quimica

Biologica) - Instituto de Bioquimica Medica - UFRJ, Coordenação de Aperfeiçoamento

de Pessoal de Nível Superior. Advisor: Martha Meriwether Sorenson.

2013:

1. Cristiane Latge de Almeida e Silva. Estudos estruturais do fator neurotrófico dopamina

cerebral (CDNF) e seus efeitos neuroprotetores contra a toxicidade de agregados de alfa-

sinucleína.. 2013. Doctoral thesis (Doutorado em Química Biológica) - Instituto de

Bioquímica Médica, Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Advisor: Debora Foguel.

2. Priscila dos Santos Ferreira da Silva. Estudos Estruturais e Celulares com a Proteína

Amiloidogênica Transtirretina: Da Proteína à Doença. 2013. Doctoral thesis (Doutorado

em Quimica Biológica) - Instituto de Bioquímica Médica, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Debora Foguel.

3. Ricardo Santanna de Oliveira. Determinantes Estruturais Envolvidos na Agregação de

Proteínas: Uma Abordagem In vitro e In silico. 2013. Doctoral thesis (Doutorado em

Química Biológica) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Debora Foguel.

4. Tiago Veltri Ormastroni da Trindade. Instabilidade da troponina C cardíaca mutante

D145E associada à cardiomiopatia amplifica o fenótipo de alta sensibilidade ao Ca2+ em

temperaturas próximas à fisiológica. 2013. Doctoral thesis (Doutorado em Quimica

Biologica) - Instituto de Bioquimica Medica - UFRJ, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Martha Meriwether Sorenson.

AL 3 Associated Laboratory of Proteins Structure Determination by NMR

(Coordinator: Fábio Almeida – UFRJ)


2016:

1. Anwar Iqbal. Análise estrutural de mutantes de tioredoxina. 2016. Doctoral thesis

(Doutorado em Química Biológica) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint supervisor: Ana

Paula Canedo Valente

2. Iamara da Silva Andrade. Identificação da interação entre as proteínas NS1 e do Vírus da

Dengue sorotipo 2 e GAPDH: influência da proteína viral no metabolismo e na

morfologia mitocondrial. 2016. Doctoral thesis (Doutorado em Ciências Biológicas

195


195

(Biofísica)) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Ronaldo da Silva Mohana Borges.

2015:

1. Aline Batista. Caracterização Estrutural de alergenos por RMN. 2015. Doctoral thesis

(Doutorado em Química Biológica) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Ana Paula

Canedo Valente.

2. Aracelys Lopez Catilla. Emprego da Espectroscopia de RMN no Estudo da Interação de

Sticholysinas e modelos miméticos de Membrana e em Genomica Estrutural de

Tripanossomatídeos. 2015. Doctoral thesis (Doutorado em Química Biológica) -

Universidade Federal do Rio de Janeiro, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Jose Ricardo Murari Pires.

3. Gustavo Tavares Ventura. Caracterização estrutural e estudos de interação com inibidores

específicos da proteína não-estrutural 3 (NS3) do vírus da hepatite C (HCV). 2015.

Doctoral thesis (Doutorado em Ciências Biológicas (Biofísica)) - Universidade Federal

do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Advisor: Ronaldo da Silva Mohana Borges.

4. Jonas Nascimento Conde. Interação entre proteína NS1 do vírus da dengue 2 e as

proteínas humanas vitronectina e plasminogênio. 2015. Doctoral thesis (Doutorado em

Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Ronaldo da Silva

Mohana Borges

5. Talita Lopes Santos. Influência da seleção de conformação na especificidade de peptídeos

antimicrobianos. 2015. Doctoral thesis (Doutorado em Química Biológica) -


Científico e Tecnológico. Advisor: Ana Paula Canedo Valente.

2014:

1. Adolfo Moraes. Alergenos: Construção de Moléculas Hipoalergênicas: da Caracterização

Estrutural às Vacinas Alergeno-específicas. 2014. Doctoral thesis (Doutorado em

Química Biológica) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Ana Paula Canedo Valente. Joint

supervisor: Fabio Ceneviva Lacerda Almeida.

2. Diego Allonso R. dos Santos da Silva. Avaliação do potencial da proteína viral NS1 e da

proteina humana High Mobility Group Box 1 (HMGB1) como biomarcadores

prognósticos de dengue. 2014. Doctoral thesis (Doutorado em Ciências Biológicas

(Biofísica)) - Universidade Federal do Rio de Janeiro, Fundação Carlos Chagas Filho de

Amparo à Pesquisa do Estado do RJ. Advisor: Ronaldo da Silva Mohana Borges.

3. Luciana Elena S. F. Machado. Determinação da Estrutura do domínio 10 da proteína C

ligadora de miosina e sua interação com LMM. 2014. Doctoral thesis (Doutorado em

Química Biológica) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Fabio Ceneviva Lacerda

Almeida. Joint supervisor: Ana Paula Canedo Valente.

4. Tatiana Kelly Fidalgo. Análise do metaboloma salivar e microbiota cariogênica de

crianças com cárie e após tratamento dental. 2014. Doctoral thesis (Doutorado em

Odontologia) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Joint supervisor: Ana Paula Canedo Valente.

5. Valéria de Abreu da Silva Bastos. Binômio Mãe-Bebê: Saúde bucal, perfil salivar e

aleitamento materno. 2014. Doctoral thesis (Doutorado em Odontologia) - Universidade

Federal do Rio de Janeiro, . Advisor: Ana Paula Canedo Valente.

2013:

1. Cristiane Latgé de Almeida e Silva. Determinação da estrutura do fator neurotrófico

dopamina cerebral (CDNF) e seu efeito protetor contra a toxicidade de oligômeros de

alfa-sinucleína, proteína envolvida na doença de parkinson. 2013. Doctoral thesis

(Doutorado em Química Biológica) - Universidade Federal do Rio de Janeiro, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Joint supervisor: Marcius da

Silva Almeida.

196


196

AL 4 Associated Laboratory of Pharmacologic Proteomic

(Coordinator: Russolina Zingali – UFRJ)


2016:

1. Ana Carolina Leal de Oliveira. Cooperação entre neutrófilos e vesículas extracelulares na

trombose associada ao câncer. 2016. Doctoral thesis (Doutorado em Química Biológica) -


Científico e Tecnológico. Advisor: Robson de Queiroz Monteiro.

2. Rosane Nunes. Estudo de Biofertlizantes em Plantas de Milho. 2016. Doctoral thesis

(Doutorado em Bioquímica) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior Joint supervisor: Russolina Benedeta

Zingali.

2015:

1. Felipe Roberto Borba Pereira. Caracterização parcial e atividades biológicas do veneno

da aranha brasileira Lasiodora sp. (Aranae: Theraphosidae). 2015. Doctoral thesis

(Doutorado em Bioquímica e Fisiologia) - Universidade Federal de Pernambuco,

Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco. Advisor:

Russolina Benedeta Zingali.

2. Ricardo Teixeira Araujo. Efeitos da APH na imunogenicidade do veneno de Bothrops

jararacussu. 2015. Doctoral thesis (Doutorado em Quimica Biologica) - Instituto de

Bioquímica Médica /CCS / UFRJ, Conselho Nacional de Desenvolvimento Científico e

Tecnológico. Advisor: Russolina Benedeta Zingali.

2014:

1. Andreia da Silva de Oliveira. Papel da trombomodulina na migração celular de linhagens

de melanoma humano. 2014. Doctoral thesis (Doutorado em Química Biológica) -


Científico e Tecnológico. Advisor: Robson de Queiroz Monteiro.

2. Leonardo de Figueiredo Vilela. Engenharia Metabólica de Saccharomyces cerevisiae

visando melhorar a eficiência da fermentação de misturas contendo hexoses e pentoses.

2014. Doctoral thesis (Doutorado em Bioquímica) - Universidade Federal do Rio de

Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint supervisor:

Bianca Cruz Neves.

3. Marjolly Caruso Brígido. Proteoma da célula Hep G2 infectada pelo virus da Dengue.

2014. Doctoral thesis (Doutorado em Química Biológica) - Universidade Federal do Rio

de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor:

Russolina Benedeta Zingali.

2013:

1. Camilla de Souza Borges. Correlação entre a proteína oncogêncica Bcr-Abl e o receptor

PAR-1 revelam um novo alvo para o tratamento da leucemia mielóide crônica. 2013.

Doctoral thesis (Doutorado em Química Biológica) - Universidade Federal do Rio de

Janeiro, . Advisor: Robson de Queiroz Monteiro.

2. Reinaldo Barros Geraldo. Estudo das Desintegrinas Derivadas de Serpentes:

Bioinformática Estrutural, Biologia Molecular e Estudos in vitro. 2013. Doctoral thesis

(Doutorado em Quimica Biologica) - Instituto de Bioquímica Médica /CCS / UFRJ,

Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Russolina

Benedeta Zingali.

3. Vanessa Sandim. Analise proteomica da Urina de pacientes com cancer renal. 2013.

Doctoral thesis (Doutorado em Quimica Biologica) - Instituto de Bioquímica Médica

/CCS / UFRJ, Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Advisor: Russolina Benedeta Zingali.

197


197


Molecular Modeling

(Coordinator: José Daniel Figueroa Villar – IME)


2016:

1- Elaine da Conceição Petronilho Síntese e Avaliação de Novos Potenciais Inibidores e

Reativadores da Acetilcolinesterase. 2016. , Coordenação de Aperfeiçoamento de Pessoal

de Nível Superior. Advisor: Jose Daniel Figueroa-Villar.

2- Jacqueline Santos Cruz Síntese de determinados da citrinina e guanidina para ação

bacteriana. 2016. , Coordenação de Aperfeiçoamento de Pessoal de Nível

Superior. Advisor: Jose Daniel Figueroa-Villar.

3- Sirlene Oliveira Farncisco de Azeredo Síntese e avaliação biológica de derivados da

fenanthrenoquinona e da 1,4-naftoquinona. 2016. , Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Advisor: Jose Daniel Figueroa-Villar.

2015:

1. Marcelle de Souza Ferreira. "Síntese e avaliação de novos potenciais fármacos derivados

do benzilideno barbiturato e análogos". 2015. Doctoral thesis (in Chemistry) - Instituto

Militar de Engenharia, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Advisor: Jose Daniel Figueroa-Villar.

2. Jorge Willian Moreira de Souza. "Avaliação de Intercalação em DNA do Potencial

Radiossensibilizador dos Fármacos Azul de Metileno e 1,10-Fenantrolina como

Adjuvantes em Protocolo de Quimiorradioteraia Antitumor de Mama". 2015. Doctoral

thesis (in Biological Sciences (Biophysics)) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. CoAdvisor: Jose Daniel

Figueroa-Villar.

2014:

1. Evelyn F. Guimaraes. "Desenvolvimento e certificação de material de referência em

hidrocarbonetos policícliocs aromáticos (HPAs) e sua aplicação na avaliação de

contaminação de etanol combustível". 2014. Doctoral thesis (in Chemistry) - Instituto

Militar de Engenharia, INMETRO. Advisor: Jose Daniel Figueroa-Villar.

2. Simone Sacramento Valverde. "Síntese e Avaliação Biológica de Enaminas e

Quinolonas". 2014. Doctoral thesis (in Chemistry) - Instituto Militar de Engenharia.


2013:

1. Leandro José de Assis Caracterização Cinética da Ser/thr Fosfatase SIT4 e seu Papel na

Regulação da Piruvato Descarboxilase 1 por Fosforilação em Saccharomyces cerevisiae.

2013. , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Co-Advisor: Jose

Daniel Figueroa-Villar.

AL 06 - Associate Laboratory of Proteins and Proteomic Heterologous Expression

(Coordinator: Hernan Terenzi - UFSC)


2015:

1. Priscila Martins. Inibidores de PtpA e B. 2015. Doctoral thesis (in Biochemistry) -

Universidade Federal de Santa Catarina, Coordenação de Aperfeiçoamento de Pessoal de

Nível Superior. Advisor: Hernan Francisco Terenzi.

2. Tiago Bortolotto. Hidrolases sintéticas ancoradas em sistemas nanoestruturados. 2015.

Doctoral thesis (in Biochemistry) - Universidade Federal de Santa Catarina, Coordenação

de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Hernan Francisco Terenzi.

2014:

1. Carolina Pereira Tavares. Fatores de transcrição em plantas. 2014. Doctoral thesis (in

Biochemistry) - Universidade Federal de Santa Catarina, Coordenação de

198


198

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Hernan Francisco Terenzi.

2013:

1. Angela Menegatti. Inibidores de tirosina fosfatases. 2013. Doctoral thesis (in

Biochemistry) - Universidade Federal de Santa Catarina, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Hernan Francisco Terenzi.

2. Jean Borges Bertoldo. Lipases termotolerantes. 2013. Doctoral thesis (in Biochemistry) -



AL_7- Associated Laboratory of Proteins Biochemistry

(Coodinator: Carlos Henrique Inácio Ramos. UNICAMP)


2016:

1. Fabán Villata Romero. “Análise estrutural e funcional de metalo- e serina proteases de

veneno de serpentes”. 2016. Doctoral thesis in Science– Universidade Estadual de

Campinas,

2015:

1. Glaucia Melina Squizato Pinheiro. Doctoral thesis. Title: “Caracterização estrutural e

funcional das chaperonas moleculares SsHSP21.5-mt e SsHSP22.3-cp de Saccharum ssp.

(cana-de-açúcar)" 2015. Advisor: Carlos Ramos

2014: 1. Daniela Pott Marinho Ballottin. “CARACTERIZAÇÃO DE NANOPARTÍCULAS DE

PRATA E SUA APLICAÇÃO NA PRODUÇÃO DE TECIDOS

ANTIMICROBIANOS”. 2014. Doctoral thesis in Sciences- Universidade Estadual de

Campinas. Advisor: Ljubica Tasic

2. Letícia Maria Zanphorlin. Doctoral thesis. Title: “Hsp90 humana: interação com a co-

chaperona tom70 e efeito do celastrol na estrutura e função" 2014. Advisor: Carlos

Ramos

2013:

1. Almas Taj Awan. “Hidrólise de bagaço de laranja para produção de etanol”. 2013.

Doctoral thesis in Science - Universidade Estadual de Campinas. Advisor: Ljubica Tasic

2. Viviane Cristina Heinzen da Silva. Doctoral thesis. Title: “Investigação da interação das

chaperonas moleculares Hsp100 e Hsp90 com outras chaperonas, com proteínas-clientes

e com um fator de transcrição de choque térmico." 2013. Advisor: Carlos Ramos

AL 8 - Associated Laboratory of Macromolecules Crystallization

(Coodinator: Marcelo Santos Castilho -UFBA)

Total of 0 Doctoral thesis completed during the whole period.

AL 9 - Associated Laboratory of Cellular Ultrastructure Hertha Meyer (Coordinator: Wanderley de Souza -IBCCF/UFRJ)


2016:

1. Aline Cristina De Abreu Moreira De Souza. Envolvimento de Receptores P2 durante a

Toxoplasmose crônica. 2016. Instituto de Biofísica Carlos Chagas Filho. Advisores:

Robson Coutinho Silva e Rossiane Vommaro.

2. Juliana de Araujo Portes. AVALIAÇÃO DO EFEITO ANTI-Toxoplasma gondii DE

COMPOSTOS METALOCOMPLEXOS.. 2016. Doctoral thesis (in Biological Sciences

(Biophysics)) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Wanderley de Souza.

199


199

3. Viviane Sant'anna de Souza. Avaliação da atividade da ivermectina, análogos de

fosfolipídios e complexos metálicos sobre nematóides da super família rabditoidea. 2016.

Doctoral thesis (in Biophysics) - Instituto de Biofísica Carlos Chagas Filho, Coordenação

de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Wanderley de Souza.

2015:

1. Carolina Moura Costa Catta Preta. Endossimbiose em tripanossomatídeos: estudo do

ciclo celular e da composição glicoprotéica de dois organismos intimamente relacionados.

2015. Instituto de Biofísica Carlos Chagas Filho. Advisora: Maria Cristina Motta.

2. Guilherme Luiz Pinheiro. O potencial da microbiota bacteriana do caracol gigante

africano (Achatinafulica) na produção de enzimas celulolíticas. 2015. Instituto de

Biofísica Carlos Chagas Filho. Advisores: Wanderley de Souza e Susana Frasés.

3. Silvana Sant´Anna de Souza. Estudo do genoma, do transcriptoma e do cinetoplasto de

Angomonas deanei e Strigomonas culicis: dois tripanossomatídeos que contêm simbionte.

2015. Instituto de Biofísica Carlos Chagas Filho. Advisoras: Maria Cristina Motta e

Rosane Silva.

4. Sueli de Souza Lima. Morfologia e taxonomia de nematoides Spirurida, parasitos de

anfíbios, de repteis e de aves nas microrregiões de Juiz de Fora, Cataguases e Ubá, Zona

da Mata mineira, Minas Gerais, Brasil. 2015. Instituto de Biofísica Carlos Chagas Filho.

Advisores: Wanderley de Souza e Jairo da Silva Pinheiro.

5. Tatiana Christina Paredes Santos. Estudo morfológico da cistogênese do Toxoplasma

gondii e sua interação com a célula hospedeira. 2015. Instituto de Biofísica Carlos Chagas

Filho. Advisoras: Marcia Attias e Rossiane Vommaro.

2014:

1. Aline AraujoZuma. Estudo do mecanismo de ação da Camptotecina e do Berenil no

Trypanosoma cruzi: lidando com a desorganização do DNA nuclear e mitocondrial. 2014.

Instituto de Biofísica Carlos Chagas Filho. Advisora: Maria Cristina Motta

2. Ivone Rosa de Andrade. Organização estrutural de Tritrichomonas foetus e Trichomonas

vaginalis e caracterização bioquímica da costa de T. foetus. 2014. Instituto de Biofísica

Carlos Chagas Filho. Advisores: Marlene Benchimol e Wanderley de Souza.

3. Joseane Lima Prado Godinho. Novas abordagens e estratégias na avaliação biológica de

fármacos para o tratamento das Leishmanioses. 2014. Instituto de Biofísica Carlos

Chagas Filho. Advisores: Juliany Cola Fernandes Rodrigues e Wanderley de Souza.

4. Juliana Cunha Vidal. Transições morfológicas na via endocítica nas diferentes formas

evolutivas de T. cruzi. 2014. Instituto de Biofísica Carlos Chagas Filho. Advisora:

Narcisa L. Cunha e Silva.

5. Renata Travassos de Lima Carvalho. Estudo da ultraestrutura e mobilidade do conóide de

Toxoplasma gondii. 2014. Instituto de Biofísica Carlos Chagas Filho. Advisora: Marcia

Attias.

2013:

1. Allan Cezar de Azevedo Martins. Simbiose em tripanossomatídeos: a influência da

bactéria simbiótica no metabolismo energético mitocondrial e na síntese lipídica do

protozoário hospedeiro. 2013. Instituto de Biofísica Carlos Chagas Filho. Advisores:

Maria Cristina Motta e Marcelo Einicker Lamas.

2. Emile Santos Barrias. Participação das diferentes vias endocíticas na infecção celular do

Trypanosoma cruzi. 2013. Instituto de Biofísica Carlos Chagas Filho. Advisora: Tecia

Maria Ulisses de Carvalho.

3. Lorian Cobra Straker. Descrição Morfológica e Análise Filogenética de Microestruturas

de Penas de Procellariiformes. 2013. Instituto de Biofísica Carlos Chagas Filho.

Advisora: Marcia Attias. Co-Advisor: Marcos André Raposo Ferreira.

4. Phercyles Veiga dos Santos. Quimioterapia anti Trypanosoma cruzi: Atividade de

Compostos com ação na biossíntese de ergosterol e histonas desacetilases da classe III.

2013. Instituto de Biofísica Carlos Chagas Filho. Advisores: Tecia Maria Ulisses de

Carvalho e Wanderley de Souza.


Biological Systems

200


200

( Coodinator: Paulo Mascarello Bisch - IBCCF/UFRJ)


2016:

1. DANIEL MOREIRA DA COSTA LEITE. CARACTERIZAÇÃO DA INTERAÇÃO DO

FATOR TRANSCRICIONAL PHOB COM REGIÕES REGULADORAS DO DNA:

IMPLICAÇÕES NA FISIOLOGIA E PATOGENICIDADE DA VIBRIO CHOLERAE.

2016. Doctoral thesis (Doutorado em Biofisica) - Instituto de Bofisica Carlos Chagas

Filho, Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Wanda

Maria Almeida von Kruger.

2015:

1. Fernanda Rios Jacinavicius. ASPECTOS MORFOLÓGICOS, FISIOLÓGICOS E

BIOQUÍMICOS E SUAS RELAÇÕES COM PRODUÇÃO DE MICROCISTINAS EM

CEPAS DE Microcystis aeruginosa (CYANOBACTERIA). 2015. Doctoral thesis

(Doutorado em Biodiversidade Vegetal e Meio Ambiente) - Instituto de Botânica,

Fundação de Amparo à Pesquisa do Estado de São Paulo. Joint supervisor: Ana Beatriz

Furlanetto Pacheco.

2. Pedro Victor Renault de Barros. Estudos Computacionais Sobre a Dinâmica

Conformacional e a Modulação Alostérica em Cisteíno-proteases.. 2015. Doctoral thesis

(Doutorado em Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de

Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Paulo

Mascarello Bisch.

2014:

1. Mauricio Garcia de Souza Costa. A New Method to Explore the Free Energy

Lasndscapes of Large Structural Changes in Proteins: Molecular Dynamics with Exited

Normal Modes (MDeNM). 2014. Doctoral thesis (Doutorado em Ciências Biológicas

(Biofísica)) - Universidade Federal do Rio de Janeiro, Coordenação de Aperfeiçoamento

de Pessoal de Nível Superior. Advisor: Paulo Mascarello Bisch.

2013:

1. João Lídio da Silva Gonçalves Vianez Júnior. Modelagem Molecular Aplicada a

Genômica Estrutural e Funcional de Espécies de Vibrio: Estudo do Regulon PHO.. 2013.


do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Advisor: Paulo Mascarello Bisch.

AL 11 - Associated Laboratory of Microscopy

(Coordinators: Thais Cristina Baeta Soares Souto Padrón / Ulysses Garcia Casado Lins

IMPPG/UFRJ)


2014:

1. Viviana Karina Morillo Lopez. Isolamento, cultivo e análise genômica de Magnetofaba

australis cepa IT-1, um novo gênero de bactéria magnetotática isolada do Hemisfério Sul.

2014. Universidade Federal do Rio de Janeiro. Advisor: Ulysses Garcia Casado Lins.

2013:

1. Roberta Ferreira Cura das Neves - “Trypanosoma cruzi: Dinâmica da superfície celular

papel em diferentes cepas” – 2013. Doctoral thesis in Science (Microbiology)Instituto de

Microbiologia Paulo de Góes – UFRJ. Advisor: Thaïs Cristina Baeta Soares Souto

Padrón

2. Anne Cristine Silva Fernandes. - “Leishmania amazonensis: participação da fosfolipase

A2 independente de cálcio na diferenciação cellular e modulação de fatores de virulência

e infecção” 2013. Doctoral thesis in Science (Microbiology)Instituto de Microbiologia

Paulo de Góes – UFRJ. Advisor: Thaïs Cristina Baeta Soares Souto Padrón

3. Fernando Pereira de Almeida. Aplicação da microscopia de varredura confocal a laser e

201


201

microscopia eletrônica de varredura ambiental no estudo da morfologia e crescimento de

biofilmes bacterianos e fungos filamentosos. 2013. Universidade Federal do Rio de

Janeiro. Advisor: Ulysses Garcia Casado Lins.

AL 12 - Associated Laboratory of Cellular Ultrastructure

(Coodinator: Marlene Benchimol – IBCCF/UFRJ and Unigranrio)


2014:

1. Ivone Rosa. Organização estrutural de Tritrichomonas foetus e Trichomonas vaginalis e

caracterização bioquímica da costa de T. foetus. 2014. Doctoral thesis (Ciências

Biológicas (Biofísica) - Universidade Federal do Rio de Janeiro- Advisor: Marlene

Benchimol

2. Victor do Valle Midlej. Caracterização morfológica e bioquímica do processo de

excistamento em Giardia lamblia. 2014. Doctoral thesis (Morphological Sciences) -

Universidade Federal do Rio de Janeiro - Doctoral thesis: Advisor: Marlene Benchimol

2013:

1. Antonio Pereira das Neves neto. Proteômica do pseudocisto de Trichomonas vaginalis.

2013. Doctoral thesis (Programa de Ciências Morfológicas) - Universidade Federal do

Rio de Janeiro- Advisor: Marlene Benchimol

2. Dirceu Esdras Teixeira. Uma nova abordagem de ensino, utilizando protozoários

patogênicos. 2013. Doctoral thesis (Biochemistry) - Universidade Federal do Rio de

Janeiro- Advisor: Marlene Benchimol and Wanderley de Souza (AL 9)

AL 13 - Associated Laboratory of Structural Biothecnology

(Coodinator: Celso B. Sant'Anna Filho -INMETRO)

Total of 0 Doctoral thesis completed during the whole period.


(Coordinator: Edilene Oliveira da Silva – UFPA.)


2016:

1. Davi Marcos Soiza de Oliveira. PERFIL COMPARATIVO DA EXPOSIÇÃO DE

SÍTIOS DE CARBOIDRATOS ENCONTRADOS NA SUPERFÍCIE DO EPITÉLIO

INTESTINAL DE LUTZOMYIA LONGIPALPIS (DIPTERA, PISYCODIDAE) DO

ESTADO DO PARÁ. 2016. Doctoral thesis (in Biology of Infectious and Parasitic

Agents) - Universidade Federal do Pará, . Advisor: Edilene Oliveira da Silva.

2. Luis Henrique Seabra de Farias. Estudo da Ação da Crotoxina Sobre o Perfil de Ativação

de Macrófagos Peritoneiais Infectados com Leishmania (leishmania) amazonensis. 2016.

Doctoral thesis (in Biology of Infectious and Parasitic Agents) - Universidade Federal do

Pará, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Edilene

Oliveira da Silva.

2013:

1. Ana Paula Drummond Rodrigues. "Ácido kójico: um bioproduto com ação leishmanicida

para o tratamento tópico de leishmaniose cutânea experimental em hamsters causada por

Leishmania (Leishmania) amazonensis". 2013. Doctoral thesis in Neurosciences and Cell

Biology. Universidade Federal do Pará. Advisor Edilene Oliveira da Silva

AL 15 - Associated Laboratory of Microscopy CETENE (Coodinator: Christina Alves Peixoto - Fundação Oswaldo Cruz)

202


202


2016:

1. Ana Karolina Santana Nunes. AVALIAÇÃO DOS EFEITOS DO INIBIDOR DE

FOSFODIESTERASE-5 SOBRE OS MECANISMOS REGULATÓRIOS DA

NEUROINFLAMAÇÃO, EM MODELO DE DESMIELINIZAÇÃO INDUZIDO EM

CAMUNDONGOS C57BL/6 WILD TYPE E KNOCKOUT PARA iNOS. 2016.

Doctoral thesis (Doutorado em Ciências Biológicas) - Universidade Federal de

Pernambuco, Fundação de Amparao a Pesquisa do Estado de Pernambuco. Advisor:

Christina Alves Peixoto.

2. Edlene Lima Ribeiro. CARACTERIZAÇÃO DOS MECANISMOS ANTI-

INFLAMATÓRIOS DA DIETILCARBAMAZINA EM MODELO MURINO DE

INFLAMAÇÃO CRÔNICA E HIPERTENSÃO PULMONAR INDUZIDA POR

MONOCROTALINA. 2016. Doctoral thesis (Doutorado em Ciências Biológicas) -

Universidade Federal de Pernambuco, Fundação de Amparao a Pesquisa do Estado de

Pernambuco. Advisor: Christina Alves Peixoto.

3. Rayana Leal de Almeida Luna. Influência de citocinas e fatores de crescimento em

modelos murinos de pré-eclâmpsia e de perda gestacional: alvos terapêuticos alternativos

na prevenção do aborto na má-formação vascular fetal. 2016. Doctoral thesis (Doutorado

em Ciências Biológicas) - Universidade Federal de Pernambuco, Fundação de Amparao a

Pesquisa do Estado de Pernambuco. Advisor: Christina Alves Peixoto.

2015:

1. Amanda Karolina Soares e Silva. AVALIAÇÃO DO MECANISMO DE AÇÃO DO

DERIVADO TIAZOLIDINICO GQ-02 SOBRE A RESISTÊNCIA A INSULINA,

ESTEATOSE HEPÁTICA E ATEROSCLEROSE EM CAMUNDONGOS

HIPERLIPIDÊMICOS. 2015. Doctoral thesis (Doutorado em Ciências Biológicas) -

Universidade Federal de Pernambuco, Conselho Nacional de Desenvolvimento Científico

e Tecnológico. Advisor: Christina Alves Peixoto.

2. Fabiana Oliveira dos Santos Gomes. AVALIAÇÃO DOS EFEITOS DO INIBIDOR DE

FOSFODIESTERASE-5 SOBRE A PRÓSTATA DE CAMUNDONGOS C57BL/6

WILD TYPE E KNOCKOUT PARA iNOS.. 2015. Doctoral thesis (Doutorado em

Ciências Biológicas) - Universidade Federal de Pernambuco, Fundação de Amparao a

Pesquisa do Estado de Pernambuco. Advisor: Christina Alves Peixoto.

2014:

1. Karla Patrícia de Sousa Barbosa. Avaliação da ação anti-inflamatória de novos derivados

tiazolidínicos em modelo de pleurisia induzida por carragenina em camundongos. 2014.

Doctoral thesis (Doutorado em Ciências Biológicas) - Universidade Federal de

Pernambuco, Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco.

Joint supervisor: Christina Alves Peixoto.

2. Sura Wanessa Santos Rocha. ANÁLISES DOS EFEITOS DA DIETILCARBAMAZINA

(DEC) SOBRE O PROCESSO INFLAMATÓRIO HEPÁTICO AGUDO E CRÔNICO

EM CAMUNDONGOS C57BL/6J. 2014. Doctoral thesis (Doutorado em Ciências

Biológicas) - Universidade Federal de Pernambuco, Fundação de Amparo à Ciência e

Tecnologia do Estado de Pernambuco. Advisor: Christina Alves Peixoto.

2013:

1. Ana Janaína Jeanine Martins Lemos. Adminsitrção Associativa do cloridato de

metformina e melatonina na reversão da polcistose ovariana e os efeitos sobre o fígado e

reprodução em ratas albinas. 2013. Doctoral thesis (Doutorado em Biociência Animal) -

Universidade Federal Rural de Pernambuco, Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Joint supervisor: Christina Alves Peixoto.

2. Bruna Santos Silva. AVALIAÇÃO DOS EFEITOS DA DIETILCARBAMAZINA

SOBRE OS MECANISMOS REGULATÓRIOS DO NF-kβ NA LESÃO

HEPATOCELULAR INDUZIDA PELO ALCOOLISMO. 2013. Doctoral thesis

(Doutorado em Ciências Biológicas) - Universidade Federal de Pernambuco, Fundação de

Amparao a Pesquisa do Estado de Pernambuco. Advisor: Christina Alves Peixoto.

203


203

3. Mariana Aragão Matos Donato. ESTUDO SOBRE O MECANISMO DE AÇÃO DO

CITRATO DE SILDENAFIL NO DESENVOLVIMENTO FOLICULAR DE

CAMUNDONGOS C57BL/6. 2013. Doctoral thesis (Doutorado em Ciências Biológicas)

- Universidade Federal de Pernambuco, Fundação de Amparao a Pesquisa do Estado de

Pernambuco. Advisor: Christina Alves Peixoto.

AL 16 - Associate Laboratory of Molecular And Cellular Cardiology

(Coordinator: Antonio Campos de Carvalho – IBCCF/UFRJ)


2016:

1. Camila Iansen Irion. Impacto de Células Estromais Mesenquimais na Respiração

Mitocondrial do Tecido Cardíaco após o Infarto Agudo do Miocárdio. 2016. Doctoral

thesis (in Biological Sciences - Physiology) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Regina Coeli

dos Santos Goldenberg.

2. Danúbia Silva dos Santos. Terapia com Células-tronco Embrionárias no Modelo de

Cardiomiopatia Dilatada Induzida por Doxirrubicina. 2016. Doctoral thesis (in Biological

Sciences (Physiology)) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Regina Coeli dos Santos

Goldenberg.

3. Karina Dutra Asensi. Alta Resistência ao Estresse Oxidativo: Possível Vantagem

Terapêutica das Células Estromias Mesenquimais Derivadas do Sangue Menstrual no

Infarto do Miocárdio. 2016. Doctoral thesis (in Biological Sciences - Physiology) -

Universidade Federal do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de

Nível Superior. Advisor: Regina Coeli dos Santos Goldenberg.

2015:

1. Felipe Gonçalves Carvalho. "ANÁLISE DA EXPRESSÃO DA

ENDORRIBONUCLEASE DICER EM MENINGIOMAS CEREBRAIS”. 2015.

Doctoral thesis in Phisiology - UFRJ, Advisor: Antonio Carlos Campos de Carvalho

2. Guilherme Visconde Brasil. "Células Tronco Embrionárias: Uma Nova Perspectiva

Terapêutica para a Cardiomiopatia Chagásica Experimental”. 2015. Doctoral thesis in

Phisiology - UFRJ, Advisors: Antonio Carlos Campos de Carvalho and Regina Coeli dos

Santos Goldenberg

3. Dilza Balteiro Pereira de Campos. "Diferenciação cardiogênica de uma linhagem de

células-tronco embrionárias e caracterização dos cardiomiócitos obtidos”. 2015. Doctoral

thesis in Phisiology - UFRJ, Advisors: Adriana Bastos Carvalho and Antonio Carlos

Campos de Carvalho

4. Cláudia Cardoso Marciel Escalhão. "Investigação do Uso da Polilaminina em Células

Mesenquimais Derivadas do Tecido Adiposo Canino em Lesão Medular". 2015. Doctoral

thesis in Biological Sciences (Biophysics) - UFRJ. Advisors: Regina Coeli dos Santos

Goldenberg and Tatiana Sampaio.

5. Lindalva Layse de Lima Malagueta Vieira. Papel de canais iônicos nas interações das

células tronco mesenquimais com tecido renal lesado. 2015. Doctoral thesis (in

Biochemistry and Physiology) - Universidade Federal de Pernambuco, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. CoAdvisor: Emiliano Horacio

Medei.

2014:

1. Fernanda Cristina Paccola Mesquita. "Geração e diferenciação de células-tronco de

pluripotência induzidas humanas”. 2014. Doctoral thesis in Biophysics - UFRJ, Advisors:

Adriana Bastos Carvalho and Antonio Carlos Campos de Carvalho

2. Gustavo Monnerat Cahli. Aspectos fisiopatológicos do remodelamento elétrico cardíaco

induzido pelo diabetes mellitus experimental: potencial terapêutico das células-tronco

mesenquimais de medula óssea. 2014. Doctoral thesis (in Biological Sciences

204


204

(Physiology)) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Emiliano Horacio Medei.

3. Marco Antonio Vidal Jiménez. Estudo do componente autoimune na Doença de Chagas.

2014. Doctoral thesis (in Biological Sciences - Physiology) - Universidade Federal do Rio

de Janeiro, . Advisor: Emiliano Horacio Medei.

4. Vivian Miranda Lago. "Efeito da superexpressão da proteína p2beta de T. cruzi no

coração de camundongos transgênicos”. 2014. Doctoral thesis in Biophysics - UFRJ,

Advisor: Antonio Carlos Campos de Carvalho

2013:

1. Débora Bastos Mello. "Avaliação do modelo murino para o estudo da terapia celular na

cardiomiopatia chagásica. 2013. Doctoral thesis in Biological Sciences (Physiology) -

UFRJ. Advisors: Adriana Bastos Carvalho and Regina Coeli dos Santos Goldenberg.

Leandro Vairo. "Avaliação do potencial terapêutico das células-tronco embrionárias no

infarto do miocárdio”. 2013. Doctoral thesis in Biophysics - UFRJ, Advisors: Regina

Coeli dos Santos Goldenberg and Antonio Carlos Campos de Carvalho

2. Tais Hanae Kasai Brunswick. "Caracterização das células progenitoras cardíacas e

avaliação de seu potencial terapêutico em modelo de infarto cicatrizado em ratos". 2013.

Doctoral thesis in Phisiology - UFRJ, Advisor: Antonio Carlos Campos de Carvalho

AL 17. Associated Laboratory of Ion transport physiology in health and disease

(Coodinator: Adalberto Ramón Vieyra – IBCCF/UFRJ)


2016:

1. Malek Chouchane. REPROGRAMMING OF DISTINCT ASTROGLIAL

POPULATIONS INTO SPECIFIC NEURONAL SUBTYPES IN VITRO AND IN

VIVO. 2016. Doctoral thesis (Doutorado em NEUROCIÊNCIAS) - Universidade Federal

do Rio Grande do Norte, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Advisor: Marcos Romualdo Costa. 2. Thiago Pereira de Abreu. Correlação entre malária grave e lesão renal em modelo murino.

2016. Doctoral thesis (Doutorado em Ciências Biológicas (Fisiologia)) - Universidade


Superior. Advisor: Celso Caruso Neves.

2015:

1. Diogo de Barros Peruchetti. Mecanismos moleculares induzidos por albumina no túbulo

proximal renal: papel de mTORC1/2 na excreção renal de sódio. 2015. Doctoral thesis

(Doutorado em Ciências Biológicas (Fisiologia)) - Universidade Federal do Rio de

Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Celso

Caruso Neves and Ana Acacia Caruso Neves

2. Elaine Hilário de Souza. Modulação da atividade da Cu(I)-ATPase hepática por insulina e

glucagon. 2015. Doctoral thesis (Doutorado em Ciências Biológicas (Biofísica)) -


Científico e Tecnológico. Advisor: Jennifer Lowe.

3. Gabriela Modenesi Sirtoli. Correlação entre a Na+-ATPase e o cotransportador NaPi-IIB

em células de câncer de ovário: possível papel na sobrevivência e proliferação celular.



Superior. Advisor: Celso Caruso Neves.

4. João Luiz da Silva Filho. Papel de angiotensina II (Ang II)/receptor AT1 na resposta de

linfócitos T durante a infecção pelo plasmodium berghei. 2015. Doctoral thesis


Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor:

Celso Caruso Neves and Ana Acacia Pinheiro Caruso Neves

5. Lindalva Layse Lima Malagueta Vieira. Estudo dos efeitos da metformina sobre a

corrente transitoria de saída de potássio e a repolarizaçao cardíaca em ratos. 2015.

205


205

Doctoral thesis (Doutorado em Bioquímica e Fisiologia) - Universidade Federal de

Pernambuco, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor:

Adalberto Ramon Vieyra. Joint supervisor: Emiliano H Medei (AL 16). 6. Thais Russo Abrahão. Transporte de fosfato inorgânico em Leishmania (Leishmania)

infantum e Trypanosoma brucei brucei: Caracterização, expressão e regulação do

transportador de fosfato inorgânico. 2015. Doctoral thesis (Doutorado em Curso de Pós-

graduação em Ciências (Microbiologia)) - Instituto de Microbiologia Prof. Paulo de Góes

/ UFRJ, Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Jose

Roberto Meyer Fernandes.

7. Valdilene da Silva Ribeiro. SOBRECARGA DE VITAMINA E DURANTE O

PERÍODO PRÉ-NATAL PODE REPERCUTIR SOBRE A FUNÇÃO RENAL NA

IDADE ADULTA. 2015. Doctoral thesis (Doutorado em Bioquímica e Fisiologia) -

Universidade Federal de Pernambuco, . Advisor: Ana Durce Oliveira da Paixão.

2014:

1. Clara Rodrigues Ferreira. As lesões evidentes e latentes da isquemia/reperfusão em

mitocôndrias renais e sua prevenção por células mononucleares da medula óssea

dependem dos caminhos dos elétrons até a citocromo c oxidase durante a respiração.

2014. Doutorado em Química Biológica. Universidade Federal do Rio de Janeiro.

Advisor: Adalberto R Vieyra. Joint supervisor: Antonio Galina Filho. 2. Edjair V. Cabral. Alterações renais provocadas pela sobrecarga de sal. 2014. Doutorado

em Bioquímica e Fisiologia. Universidade Federal de Pernambuco. Advisor: Ana DO

Paixão. Joint supervisor: Adalberto R Vieyra. 3. Fernanda Magalhães Ferrão. Mecanismos moleculares envolvidos no efeito de Ang II

luminal que contribuem para a homeostasia do íon Ca2+ no túbulo proximal.. 2014.


do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Advisor: Jennifer Lowe. 4. Francisco José Arnould Batista. Uroguanilina modula a (Na++K+)ATPase no túbulo

proximal: possível envolvimento das vias GMPc/PKG e PKB/mTOR. 2014. Doctoral

thesis (Doutorado em Ciências Biológicas (Fisiologia)) - Universidade Federal do Rio de

Janeiro, Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico.

Advisor: Celso Caruso Neves.

5. Juliana Dias Alves Pinto. A angiotensina-(3-4) inibe a Na+-ATPase renal de ratos

espontaneamente hipertensos por um mecanismo que envolve a participação de

heterodímeros de receptores de angiotensina II e PKA. 2014. Doutorado em Ciências

Biológicas (Biofísica). Universidade Federal do Rio de Janeiro. Advisor: Adalberto R

Vieyra. 6. Luzia da Silva Sampaio. Caracterização do Sistema Endocanabinóide em Células de

Túbulo Proximal Renal e Avaliação de sua Participação em Processo de Lesão

Promovida por Isquemia e Reperfusão. 2014. Doctoral thesis (Doutorado em Ciências

Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Marcelo Einicker Lamas.

7. Sheila Maturana Teixeira. Avaliação das subunidades da (Na+/K+)-ATPase durante o

desenvolvimento da retina de ratos e a modulação de sua atividade por citocinas. 2014.

Doctoral thesis (Doutorado em Neuroimunologia) - Universidade Federal Fluminense,

Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Luiz

Roberto Leão Ferreira.

8. Thaís Souza Silveira. Caracterização das atividades ecto-fosfatásicas da microalga

Euglena gracilis e do tripanossomatídeo Phytomonas serpens. 2014. Doctoral thesis

(Doutorado em Curso de Pós-graduação em Ciências (Microbiologia)) - Instituto de

Microbiologia Prof. Paulo de Góes / UFRJ, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Jose Roberto Meyer Fernandes.

2013:

1. Allan Cézar de Azevedo Martins. Endosimbiose em tripanosomatídeos:a influência da

bactéria simbiótica no metabolismo energético mitocondrial e na sínDoctoral thesis de

lipídios do protozoário hospedeiro. 2013. Doctoral thesis (Doutorado em Ciências

206


206

Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Joint advisor: Marcelo Einicker

Lamas.

2. Claudia Fernanda Dick. Mecanismos de captação de fosfato inorgânico em Trypanosoma

rangeli e Trypanosoma cruzi. 2013. Doctoral thesis (Doutorado em Curso de Pós-

graduação em Ciências (Microbiologia)) - Instituto de Microbiologia Prof. Paulo de Góes

/ UFRJ, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do RJ. Advisor:

Jose Roberto Meyer Fernandes.

3. Karine da Silva Verdoorn. Regeneração do tecido renal após lesão por obstrução ureteral

reversível: avaliação do tratamento com células mononucleares de medula óssea. 2013.

Doctoral thesis (Doutorado em Ciencias Biologicas - Fisiologia) - Universidade Federal


Advisor: Marcelo Einicker Lamas.

4. Leandro de Souza Silva. Angiotensina II e peptídeos relacionados: possível papel na

patogênese da malária. 2013. Doctoral thesis (Doutorado em Ciências Biológicas

(Fisiologia)) - Universidade Federal do Rio de Janeiro, Coordenação de Aperfeiçoamento

de Pessoal de Nível Superior. Advisor: Ana Acacia Pinheiro Caruso Neves and Joint

supervisor: Celso Caruso Neves.

5. Milene Rangel da Costa. Mecanismos de regeneração renal pós-isquemia mediados por

células mesenquimais humanas: uma abordagem global utilizando espectrometria de

massas Label-free MSE. 2013. Doutorado em Ciências Biológicas (Biofísica).

Universidade Federal do Rio de Janeiro. Advisor: Adalberto R Vieyra.

6. Paulo André da Silva. Mecanismos que envolvem vias de sinalização associadas à

Angiotensina II e à MAPK/ERK1/2: base das alterações no transporte de Na+ em túbulos

proximais renais causadas pela desnutrição crônica. 2013. Doutorado em Ciências

Biológicas (Fisiologia). Universidade Federal do Rio de Janeiro. Advisor: Adalberto R

Vieyra. 7. Rafael Soares Lindoso. Papel das Microvesículas e microRNAs na interação parácrina

entre células mesenquimais e renal no processo regenerativo. 2013. Doctoral thesis

(Doutorado em Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de


Marcelo Einicker Lamas.

8. Rosilane Taveira da Silva. Inter relação entre o sistema renina angiotensina e o sistema

dopaminérgico intrarrenal em cultura de células LLC-PK1. 2013. Doctoral thesis

(Doutorado em Ciencias Biologicas - Fisiologia) - Universidade Federal do Rio de

Janeiro, . Advisor: Marcelo Einicker Lamas.


(Coodinated by Prof. Julio Scharfstein- IBCCF/UFRJ)


2015:

1. Larissa Nogueira de Almeida. "Impacto do edema inflamatório no balanço de forças

entre Trypanosoma cruzi e o sistema imune inato" 2015. Doctoral thesis de Doutorado em

Ciências Biológicas - Universidade Federal do rio de Janeiro-IBCCFº, Advisor: Julio

Scharfstein

2014:

2. Erivan Schnaider Ramos Junior. "Papel do eixo Fímbria/TLR2/B2R na ativação de

células sentinelas do sistema imune inato por Porphyromonas gingivalis" 2014. Doctoral

thesis de Doutorado em Ciências Biológicas- Universidade Federal do Rio de Janeiro-

IBCCFº, Advisor: Julio Scharfstein

AL 19 - Associated Laboratory of Cellular and Molecular Neurology

(Coordinator: Rosalia Mendez Otero)

207


207


2016:

1. Alane Bernardo Ramos. Efeito a longo prazo da terapia com celulas mononucleoses de

medula óssea na isquemia cerebral global em ratos. 2016. Doctoral thesis (Doutorado em

Ciências Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Rosalia Mendez-Otero.

2. Helio Rodrigues da Silva. Estudo da eficácia da marcação e monotiramento de células

tronco mesenuimais de medula óssea aplicada ao modelo de isquemia cerebral focal.

2016. Doctoral thesis (Doutorado em Ciências da Saúde) - Faculdade de Ciências

Médicas da Santa Casa de São Paulo, . Joint supervisor: Rosalia Mendez-Otero.

2015:

1. Louise Alessandra Mesentier Louro. Investigation of cellular and pharmacological

therapies in a model of optic nerve injury. 2015. Doctoral thesis (Doutorado em Ciências

Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Rosalia Mendez-Otero.

2. Andréa Marins Damasceno Bomfim. Efeito da Terapia Celular em Modelo de Lesão

Medular Unilateral: Correlação Morfológica e Funcional. 2015. Doctoral thesis

(Doutorado em Biofisica) - Universidade Federal do Rio de Janeiro, Conselho Nacional

de Desenvolvimento Científico e Tecnológico. Advisor: Rosalia Mendez-Otero.

2014:

1. Mariana Araya de Godoy. Avaliação do potencial neuroprotetor das células-tronco

mesenquimais da medula óssea em um modelo in vitro da doença de Alzheimer. 2014.



Advisor: Rosalia Mendez-Otero.

2013:

1. Paulo Henrique Rosado de Castro. Rastreamento e Quantificação de Células

Mononucleares de Medula Óssea marcadas com 99mTecnécio em Terapias Celulares.

2013. Doctoral thesis (Doutorado em Medicina (Radiologia)) - Universidade Federal do

Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint

supervisor: Rosalia Mendez-Otero.

AL 20. Associated Laboratory of Inflammation and Metabolism

(Coordinator: Fernando Augusto Bozza)


2016:

1. Flora Magno de Jesus Oliveira. Impacto da Pneumonia Grave no Sistema Nervoso

Central: Efeitos de Curto e Longo Prazo. 2016. Doctoral thesis (Doutorado em Biologia

Celular e Molecular) - Fundação Oswaldo Cruz, . Advisor: Fernando Augusto Bozza.

2. Isabel Mattos Medeiros de Moraes. Estudo da Ativação Plaquetária na Malária Vivax.

2016. Doctoral thesis (Doutorado em Biologia Celular e Molecular) - Fundação Oswaldo

Cruz, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Hugo

Caire de Castro Faria Neto.

3. Matheus Pinto de Oliveira. Estudos sobre o metabolismo energetico e redox do helmin to

Schistosoma mansoni. 2016. Doctoral thesis (Doutorado em Química Biológica) -


Científico e Tecnológico. Advisor: Marcus Fernandes de Oliveira.

4. Renata Tiemi Okuro. Avaliação da SínDoctoral thesis de Ceramida por Vias Enzimáticas

Distintas e seu Efeito na Lesão Pulmonar Induzida por Lipopolissacarídeo na morfologia

e mecânica pulmonar, infiltração e apoptose neutrofílica, níveis de citocinas e estresse

oxidativo. 2016. Doctoral thesis (Doutorado em Ciências Biológicas (Fisiologia)) -


Científico e Tecnológico. Advisor: Walter Araujo Zin.

208


208

2015:

1. Mariana Gisely Amarante T.da Cunha. Papel do Receptor CCL2 no Aprendizado e no

Processo de Consolidação de Memória.. 2015. Doctoral thesis (Doutorado em Biologia

Celular e Molecular) - Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Hugo Caire de Castro Faria Neto.

2. Mariana Nascimento Machado. Terapia com Células Mononucleares Derivadas de

Medula Óssea em Modelo Experimental de Enfisema Pulmonar Induzido por Papaína.



Superior. Advisor: Walter Araujo Zin.

3. Natalia Vasconcelos Casquilho. Potencial Anti-oxidante do LASSBio 596 Via Oral em

Camundongos Intoxicados por Microscistina-LR. 2015. Doctoral thesis (Doutorado em

Ciências Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro, Coordenação

de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Walter Araujo Zin.

4. Rodrigo Teixeita Amancio. Disfunção cognitiva e HIV: Identificação de biomarcadores

para o diagnóstico precoce.. 2015. Doctoral thesis (Doutorado em Biologia Celular e

Molecular) - Fundação Oswaldo Cruz, . Advisor: Fernando Augusto Bozza

2014:

1. Bruno Curty Bergamini. Comparação entre a Pressão Positiva ao Final da Expiração que

Corresponde a Mínima Elastância Obtida a partir da Manobra de Titulação Lenta ou

Rápida. 2014. Doctoral thesis (Doutorado em Engenharia Biomédica) - Universidade


Superior. Advisor: Alysson Roncally Silva Carvalho.

2. Cássia Righy Shinotsuka. RESPOSTA INFLAMATÓRIA SECUNDÁRIA AO

ACIDENTE VASCULAR ENCEFÁLICO HEMORRÁGICO ? ANÁLISE DE

CITOCINAS, PRODUTOS DO METABOLISMO DO HEME E MARCADORES DE

ESTRESSE OXIDATIVO. 2014. Doctoral thesis (Doutorado em Pesquisa Clinica em

Doenças Infecciosas) - Fundação Oswaldo Cruz, . Advisor: Fernando Augusto Bozza.

3. Eugenio Hottz. Mecanismos de Ativação Plaquetária na Infecção pelo Vírus da Dengue:

caracterização de marcadores de gravidade e identificação de novos alvos terapêuticos..

2014. Doctoral thesis (Doutorado em Biologia Celular e Molecular) - Fundação Oswaldo

Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor:

Fernando Augusto Bozza.

4. Luciana Camilo. Ventilação Variável: Avaliação de um Novo Modo Ventilatório em

Pacientes Ventilados Mecanicamente. 2014. Doctoral thesis (Doutorado em Instituto de

Biofísica Carlos Chagas Filho) - Universidade Federal do Rio de Janeiro, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Alysson Roncally Silva

Carvalho.

5. Mariana Barcellos Avila. Repercussões do Recrutamento Alveolar e Estratégia

Ventilatória Protetora em Modelo de Lesão Pulmonar Heterogênea. 2014. Doctoral thesis



Alysson Roncally Silva Carvalho.

6. Mariana Barcellos de Ávila. Repercussoes Pulmonares e Sistêmicas de Estratégias

Ventilatórias com Baixo Volume Correntee durante Anestesia em Ratos com Pulmões

Saudáveis. 2014. Doctoral thesis (Doutorado em Ciências Biológicas (Fisiologia)) -


Científico e Tecnológico. Joint supervisor: Walter Araujo Zin.

7. Pedro Celso Braga Alexandre. Disfunção cerebral associada á sepse: papel das estatinas

na prevenção do dano cognitivo em modelo de sepse experimental. 2014. Doctoral thesis

(Doutorado em Biologia Celular e Molecular) - Instituto Cswaldo Cruz, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Hugo Caire de Castro

Faria Neto.

8. Pedro Celso Braga Alexandre. Disfunção cerebral associada à sepse: papel das estatinas

na reversão do dano cognitivo em modelo de sepse experimental. 2014. Doctoral thesis

(Doutorado em Biologia Celular e Molecular) - Instituto Oswaldo Cruz, Conselho

209


209

Nacional de Desenvolvimento Científico e Tecnológico. Joint supervisor: Fernando

Augusto Bozza.

9. Rodrigo Teixeira Amâncio. Disfução Cognitiva e HIV: Identificação biomarcadores para

o diagnóstico precoce. 2014. Doctoral thesis (Doutorado em Biologia Celular e

Molecular) - Fundação Oswaldo Cruz, . Advisor: Hugo Caire de Castro Faria Neto.

10. Valmara dos Santos Pereira. Efeito do Hipotireoidismo Farmacológico sobre a Função

Pulmonar de Ratos Wistar Adultos Jovens. 2014. Doctoral thesis (Doutorado em Ciências

Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Joint supervisor: Walter Araujo Zin.

11. Vinícios Rpsa de Oliveira. Potencial Terapêutico de LASSBIO 596 em Modelo in vivo de

Lesão Pulmonar Induzida por Cilindrospermopsina. 2014. Doctoral thesis (Doutorado em


Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Alysson Roncally Silva

Carvalho.

12. Vinicius Rosa de Oliveira. Potencial Terapêutico de LASSBio 596 em Modelo de Lesão

Pulmonar Induzida por Cilindrospermopsina. 2014. Doctoral thesis (Doutorado em


Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Walter Araujo Zin.

2013:

1. Camila Nunes Batista. Estudos sobre o metabolismo redox em Plasmodium falciparum.

2013. Doctoral thesis (Doutorado em Medicina (Doenças Infecciosas e Parasitárias)) -

Universidade Federal do Rio de Janeiro, . Joint supervisor: Marcus Fernandes de Oliveira.

2. Clarissa Bichara Magalhaes. Potencial Anti-inflamatório e Anti-oxidante do Eugenol na

Lesão Pulmonar Aguda Induzida por Lipopolissacarídeo. 2013. Doctoral thesis



Walter Araujo Zin.

3. Diogo Gomes Garcia. Sinalização de morte celular via Na+, K+ ATPase como alvo de

drogas anticancer: Estudos com o álcool perílico. 2013. Doctoral thesis (Doutorado em

Biologia Celular e Molecular) - Instituto Cswaldo Cruz, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Hugo Caire de Castro Faria

Neto.

4. Diogo Gomes Garcia. Sinalização de mortes celular via Na+, K+ aTPase como alvo de

drogas anti cancer: Estudo com alcool perilico.. 2013. Doctoral thesis (Doutorado em

Biologia Celular e Molecular) - Fundação Oswaldo Cruz, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Hugo Caire de Castro Faria Neto.

5. Douglas dos Reis Riva. O Material Particulado Fino (PM2,5) da Região Metropolitada do

Rio de Janeiro Provoca Alterações Pulmonares em Camundongos Saudáveis?. 2013.

Doctoral thesis (Doutorado em Ciências Biológicas (Fisiologia)) - Universidade Federal

do Rio de Janeiro, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do RJ.

Advisor: Walter Araujo Zin.

6. Giovanna Marcella Cavalcante Carvalho. Exposição Subcronica à Microcistina-LR:

Repercussões Pulmonares e Hepáticas da Duração do Tratamento com LASSBio 596.



Superior. Advisor: Walter Araujo Zin.

7. Maria Diana Moreira Gomes Rolim. Atividade do Diicloridrato de 2,2?-azobis (2-

metilpropionamidina) no Pulmão de Ratos. 2013. Doctoral thesis (Doutorado em Ciências

Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro, Fundação Cearense de

Apoio ao Desenvolvimento Científico e Tecnológico. Advisor: Walter Araujo Zin.

210


210

- Masters theses completed:

AL 1 - Associated Laboratory of Virus and Cancer Structural Biology

(Coordinator: Jerson Lima da Silva - Instituto de Bioquímica Médica - IBqM/UFRJ)

Total of 15 dissertations completed during the whole period, as follows:

2016:

1. Nataly Melo dos Santos. ANÁLISE DO PERFIL DE EXPRESSÃO E PAPEL

FISIOPATOLÓGICO DE ISOFORMAS DA P53 E DA OSTEOPONTINA EM

LINHAGENS CELULARES DE CARCINOMA DE ENDOMÉTRIO. 2016. Dissertation

(Mestrado em CIÊNCIAS BIOMÉDICAS (FISIOLOGIA E FARMACOLOGIA)) -

Universidade Federal Fluminense, Fundação Carlos Chagas Filho de Amparo à Pesquisa

do Estado do RJ. Advisor: Etel Rodrigues Pereira Gimba.

2015:

1. Jéssica Martins de Moura Valadares. Modulação da atividade da Na,K-ATPase e Ca-

ATPase por novos glicosídeos cardíacos semi-sintéticos com modificações na porção

glicosídica. 2015. Dissertation (Master in Ciências Farmacêuticas) - Universidade Federal

de São João Del-Rei . Advisor Leandro Augusto de Oliveira Barbosa.

2. João Gabriel Rangel Gonçalves. Bioquímica no ensino médio: desenvolvimento de uma

nova estratégia de abordagem.. 2015. Dissertation (Mestrado em Ciências Biológicas


de Pessoal de Nível Superior. Joint supervisor: Patricia Souza dos Santos.

3. Juliana Braga de Sales Andrade. Espectroscopia por Ressonância Magnética no

Transtorno Obsessivo Compulsivo,Advisor. 2015. Dissertation (Mestrado em Ciências

Morfológicas) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Fernanda Freire Tovar Moll.

4. Murilo Martins Pedrote. Estudo de Agregação da Proteína Supressora Tumoral p53 Em

Glioblastomas Humanos. 2015. Dissertation (Mestrado em Química Biológica) -


Nível Superior. Advisor: Jerson Lima da Silva.

5. Renan Amphilophilo Fernandes. O papel do inibidor de histona deacetilase, Panobinostat

no metabolismo energético de câncer de pulmão. 2015. Dissertation (Master in

Fisiopatologia Clínica e Experimental) - Universidade do Estado do Rio de Janeiro

Universidade do Estado do Rio de Janeiro , Conselho Nacional de Desenvolvimento

Científico e Tecnológico . Advisor Cláudia Vitória de Moura Gallo.

6. Tamara Fernandes. Efeito da ferritina e sobrecarga de ferro na atividade da Na,K-

ATPase. 2015. Dissertation (Master in Ciências Farmacêuticas) - Universidade Federal de

São João Del-Rei . Advisor Leandro Augusto de Oliveira Barbosa.

2014:

1. Ana Emilia Goulart. Mecanismos de ação e impactos do silencimento do RNA não

codificaste PCA3 em células de câncer de próstata. 2014. Dissertation (Mestrado em PÓS

GRADUAÇÃO STRICTO SENSU EM ONCOLOGIA) - Instituto Nacional de Câncer, .

Joint supervisor: Etel Rodrigues Pereira Gimba.

2. Kivvi Duarte de Mello. INVESTIGAÇÃO DOS MECANISMOS DE

SOBREVIVÊNCIA CELULAR ATIVADOS POR VARIANTES DE SPLICING DA

OSTEOPONTINA NO CÂNCER DE PRÓSTATA. 2014. Dissertation (Mestrado em

Programa de Pos Graduaçao em Ciencias Morfologicas) - Universidade Federal do Rio de

Janeiro, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do RJ. Joint

supervisor: Etel Rodrigues Pereira Gimba.

3. Lilian Nara David Silva. AVALIAÇÃO DA MODULAÇÃO DO PERFIL LIPÍDICO E

ATIVIDADE DA Na,K-ATPase DE CÉLULAS TUMORAIS TRATADAS COM

GLICOSÍDEOS CARDÍACOS. 2014. Dissertation (Master in CIÊNCIAS DA SAÚDE) -

Universidade Federal de São João Del-Rei . Advisor Leandro Augusto de Oliveira

Barbosa.

211


211

4. Theo Marins. Conectividade e Neuroplasticidade Cerebral por Neurofeedback.. 2014.

Dissertation (Mestrado em Ciências Morfológicas) - UFRJ / ID’Or, . Advisor: Fernanda

Freire Tovar Moll.

2013:

1. Diana Praia Borges. ADEQUAÇÃO DA PLATAFORMA DE TESTE RÁPIDO PARA O

DIAGNÓSTICO DA FEBRE AMARELA. 2013. Dissertation (Mestrado em Mestrado

Profissionalizante em Imunobiológicos) - Fundação Oswaldo Cruz, . Advisor: Ana Paula

Dinis Ano Bom.

2. Edinéa Pastro Mendes. DESENVOLVIMENTO DE CONTROLE DE PROCESSO

PARA A PRODUÇÃO DE CONJUGADO DE ANTICORPO ANTI-IgG CANINA

COM PEROXIDASE DE RAIZ FORTE. 2013. Dissertation (Mestrado em Vigilância

Sanitária) - Fundação Oswaldo Cruz, . Advisor: Ana Paula Dinis Ano Bom.

3. Monica Barboza. Taxonomia de Bloom como ferramenta para avaliação de provas de

Ciências do ensino fundamental. 2013. Dissertation (Mestrado em Mestrado Profissional)

- Instituto de Bioquímica Médica da UFRJ, . Joint supervisor: Patricia Souza dos Santos.

4. Sayonarah Carvalho Rocha. Efeito da 21-benzilideno-digoxina na junção oclusiva e na

Na,K-ATPase. 2013. Dissertation (Master in Ciências Farmacêuticas) - Universidade

Federal de São João Del-Rei Advisor Leandro Augusto de Oliveira Barbosa.


Proteins

(Coordinator: Débora Foguel- Instituto de Bioquímica Médica - IBqM/UFRJ)


2016:

1. Cinthia Lima Rocha Barbosa. Identificação de novos variantes da proteína transtirretina

em pacientes portadores de PAF no Brasil: emprego da bioinformática na caracterização

das suas propriedades amiloidogênicas. 2016. Dissertation (Mestrado em Química

Biológica) - Universidade Federal do Rio de Janeiro, . Advisor: Debora Foguel.

2015:

1. Renata Vasconcelos Barbosa da Silva. Análise da Evolução Clínica dos Pacientes com

Polineuropatia Amiloidótica Familiar (PAF) ligada a transtiretna tratados com tafamidis

ou transplante hepático, comparados com a evolução natural da doença. 2015.

Dissertation (Mestrado em Clínica Médica) - Universidade Federal do Rio de Janeiro, .

Advisor: Marcia Waddington Cruz.

2. Rodrigo Requião. Efeito de domínios alcalinos na regulação da sínDoctoral thesis de

proteínas. 2015. Dissertation (Mestrado em Química Biológica) - Universidade Federal


Advisor: Fernando Lucas Palhano Soares.

2014:

1. Aline Miyoko Sakaguchi Yamashita. A S-nitrosoglutationa redutase modula a

proliferação e fusão de mioblastos. 2014. Dissertation (Mestrado em Quimica Biologica)

- Instituto de Bioquimica Medica - UFRJ, Coordenação de Aperfeiçoamento de Pessoal

de Nível Superior. Advisor: Martha Meriwether Sorenson.

2. Liliani Aparecida Sereno Fontes de Medeiros. Aprisionando o monômero da variante não

amiloidogência da transtirretina T119M: possível terapia contra a polineuropatia

amiloidótica familiar. 2014. Dissertation (Mestrado em Química Biológica) -


Científico e Tecnológico. Advisor: Debora Foguel.

3. Luiza Fernandes. Efeitos das Micropartículas de Epigalocatequina-3-galato no processo

de agregação da α-sinucleína e remodelamento da fibra madura.. 2014. Dissertation

(Mestrado em Química Biológica) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Fernando

Lucas Palhano Soares.

212


212

4. Shenia Sbardellotto Colnaghi Novis. Aplicação das Redes Neurais Artificiais na criação

de um escore de gravidade para pacientes com Polineuropatia Amiloidótica Familiar.

2014. Dissertation (Mestrado em Clínica Médica) - Universidade Federal do Rio de

Janeiro, . Advisor: Marcia Waddington Cruz.

2013:

1. Giselly da Silva Dias. Utilização de Animações Moleculares para Divulgação Científica..

2013. Dissertation (Mestrado em Química Biológica) - Universidade Federal do Rio de

Janeiro, . Advisor: Debora Foguel.

2. Júlia Araújo de Freitas. Envolvimento do Fator de Transcrição NFAT na Doença de

Parkinson. 2013. Dissertation (Mestrado em Programa de Pós-graduação em Química

Biológica) - Universidade Federal do Rio de Janeiro, Conselho Nacional de

Desenvolvimento Científico e Tecnológico. Advisor: Debora Foguel. Joint supervisor:

Bruno Kaufmann Robbs.

AL 3 Associated Laboratory of Proteins Structure Determination by NMR

(Coordinator: Fábio Almeida – UFRJ)


2016:

1. Thayana Araujo da Cruz. PURIFICAÇÃO E CARACTERIZAÇÃO PARCIAL DE UM

BIOFÁRMACO RECOMBINANTE PRODUZIDO EM CÉLULAS CHO. 2016.

Dissertation (Mestrado em Bioquímica) - Universidade Federal do Rio de Janeiro,

Conselho Nacional de Desenvolvimento Científico e Tecnológico. Joint supervisor:

Ronaldo da Silva Mohana Borges.

2015:

1. Livia Roberta Piedade de oliveira. Saúde bucal, perfil salivar e acesso a tratamento

odontológico de crianças com diabetes tipo 1. 2015. Dissertation (Mestrado em

Odontologia (Odontopediatria)) - Universidade Federal do Rio de Janeiro, . Joint

supervisor: Ana Paula Canedo Valente.

2. Talita Stelling de Araújo. Correlação estrutura-função de proteínas humanas

correlacionadas ao câncer. 2015. Dissertation (Mestrado em Química Biológica) -


Científico e Tecnológico. Advisor: Marcius da Silva Almeida.

2014:

1. Anne Miranda Capaccia. Identificação de interações entre proteínas do fígado humano e a

proteína NS3 do vírus da Hepatite C. 2014. Dissertation (Mestrado em Ciências

Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro, Conselho Nacional de


2. Diana Pelizzari Raymundo. Caracterização estrutural da rede de interação da proteína

apoptótica BEX3: um caminho para o desenvolvimento de novas drogas anticâncer. 2014.

Dissertation (Mestrado em Química Biológica) - Universidade Federal do Rio de Janeiro,

. Advisor: Marcius da Silva Almeida.

3. Diego Rodrigues Coelho. Análise da estabilidade estrutural da proteína recombinante

NS1 do vírus da dengue. 2014. Dissertation (Mestrado em Ciências Biológicas



4. Laizes Johanson. Estudo de um peptídeo mimético ao Fator Neurotrófico Derivado de

Glia. 2014. Dissertation (Mestrado em Química Biológica) - Universidade Federal do Rio

de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor:

Marcius da Silva Almeida.

5. Rafael Mesquita Stoque. Estudo da estabilidade da proteína capsídica do vírus da dengue

e de seus mutantes por Modelagem Molecular e métodos biofísicos. 2014. Dissertation

(Mestrado em Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro,

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do RJ. Advisor: Ronaldo

da Silva Mohana Borges.

213


213

6. Ramon Pinheiro Aguiar. Determinação da Estrutura e Dinâmica de TXNIP e sua

Interação com Tioredoxina. 2014. Dissertation (Mestrado em Química Biológica) -


Científico e Tecnológico. Advisor: Fabio Ceneviva Lacerda Almeida. Joint supervisor:

Ana Paula Canedo Valente.

2013:

1. Priscila Assunção de Almeida. Metaboloma salivar e sanguíneo de crianças com

insuficiência renal crônica por meio da ressonância nagnética nuclear. 2013. Dissertation

(Mestrado em Odontologia (Odontopediatria)) - Universidade Federal do Rio de Janeiro, .

Joint supervisor: Ana Paula Canedo Valente.

AL 4 Associated Laboratory of Pharmacologic Proteomic

(Coordinator: Russolina Zingali – UFRJ)


2016:

1. Isabele Batista Campanhon Araújo. Proteínas e Peptídeos do leite de nutrizes

adolescentes: Proteômica, atividade antimicrobiana e inlfluência do período lactacional.

2016. Dissertation (Mestrado em Ciência de Alimentos) - Universidade Federal do Rio de

Janeiro, . Joint supervisor: Marcia Regina Soares da Silva.

2015:

1. Hellen Coelho. Análise de micropartículas na doença falciforme e sua correlação com

perfil pró-trombótico dos pacientes. 2015. Dissertation (Mestrado em Química Biológica)

- Universidade Federal do Rio de Janeiro, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Russolina Benedeta Zingali.

2. Leonora Vital Brazil. VALIDAÇÃO DE ANTICORPOS MONOCLONAIS ESPÉCIE-

ESPECÍFICO NO DESENVOLVIMENTO DE KIT DIAGNÓSTICO PARA A

IDENTIFICAÇÃO E EPIDEMIOLOGIA DO ACIDENTE BOTRÓPICO NO ESTADO

DO RIO DE JANEIRO.. 2015. Dissertation (Mestrado em Química Biológica) -

Universidade Federal do Rio de Janeiro, . Advisor: Russolina Benedeta Zingali.

3. Victor David. Desintegrinas do veneno de Bothrops jararaca: clonagem e expressão da

forma recombinante. 2015. Dissertation (Mestrado em Quimica Biologica) - Instituto de

Bioquímica Médica /CCS / UFRJ, Coordenação de Aperfeiçoamento de Pessoal de Nível

Superior. Advisor: Russolina Benedeta Zingali.

2014:

1. Barbara Barbosa Succar. Avaliação do Perfil Antitrombótico das Desintegrinas

Recombinantes do Veneno de Bothrops Jararaca. 2014. Dissertation (Mestrado em

Quimica Biologica) - Instituto de Bioquímica Médica /CCS / UFRJ, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Russolina Benedeta Zingali.

2. Bernardo barbosa abbês. Caracterização de mecanismos moleculares envolvidos na

interação entre Burkholderia cenocepacia e plantas hospedeiras - Oryza sativa L. e

Medicago sativa L.. 2014. Dissertation (Mestrado em Bioquímica) - Universidade Federal


Advisor: Bianca Cruz Neves.

3. Fausto Gueths Gomes. Papel de exossomos provenientes de linhagens de carcinoma

mamário humano na biologia plaquetária e coagulação sanguínea. 2014. Dissertation

(Mestrado em Química Biológica) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Robson de

Queiroz Monteiro.

4. Jéssica Pereira Machado. Clonagem, expressão e purificação do domínio de ligação a

DNA do receptor de quorum sensing RhlR de Pseudomonas aeruginosa. 2014.

Dissertation (Mestrado em Bioquímica) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint supervisor: Bianca

Cruz Neves.

214


214

5. Jorgeane Freire e Souza. Propriedades antitrombóticas dos Inibidores exógenos da

agregação plaquetária, dipetalodipina e triplatina. 2014. Dissertation (Mestrado em

Química Biológica) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Robson de Queiroz Monteiro.

6. Leticia Dobler. Expressão e caracterização functional da EstA de Pseudomonas

aeruginosa PAO1 visando à otimização da produção de biossurfactantes do tipo

raminolipídeos. 2014. Dissertation (Mestrado em Bioquímica) - Universidade Federal do

Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor:

Bianca Cruz Neves.

7. Tainá Gomes. Progressão tumoral independente da hipóxia: ativação do fator de

transcrição HIF-1 via receptores PAR1 e PAR2 em carcinoma mamário. 2014.


Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Robson de

Queiroz Monteiro.

8. Tiago Souza Salles. Efeitos antivirais dos extratos das plantas Schinus terebinthifolius e

Punica granatum na replicação do vírus Mayaro em células Vero. 2014. Dissertation

(Mestrado em Bioquímica) - Universidade Federal do Rio de Janeiro, . Advisor: Marcia

Regina Soares da Silva.

9. Wilber de Sousa Alves. Estudos de fitorremediação de solos contaminados com

hidrocarbonetos aromáticos policíclicos através da análise proteômica. 2014. Dissertation

(Mestrado em Bioquímica) - Universidade Federal do Rio de Janeiro,

PETROBRAS/CENPES. Advisor: Marcia Regina Soares da Silva.

2013:

1. Raiana Apolinário de Paula. Caracterização do perfil de glicoproteínas presentes em soros

de indivíduos sadios e pacientes com dengue clássica e hemorrágica utilizando lectina de

semente de Cratylia mollis (Cramoll 1,4). 2013. Dissertation (Mestrado em Bioquímica e

Fisiologia) - Universidade Federal de Pernambuco, Fundação de Amparo à Ciência e

Tecnologia do Estado de Pernambuco. Advisor: Russolina Benedeta Zingali.


Molecular Modeling

(Coordinator: José Daniel Figueroa Villar – IME)


2016:

1- Mariana de Oliveira Tonelli. SínDoctoral thesis e caracterização de derivados de

malononitrila e piperonal. 2016. Master’s thesis (MSc in Systems and Computation) -

Instituto Militar de Engenharia Instituto Militar de Engenharia , Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior . Advisor:Jose Daniel Figueroa-Villar.

2- Juliana de Oliveira Carneiro Brum. SínDoctoral thesis e Avaliação de Potenciais

Fparmacos par a Doença de Alzheimer. 2016. Master’s thesis (Master in Chemistry) -

Instituto Militar de Engenharia Instituto Militar de Engenharia , Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior . Advisor: Jose Daniel Figueroa-Villar.

3- Luana Gonçalves de Souza. Modelagem Molecular e RMN na Avaliação de Novos

Candidatos a Fármacos Inibidores de Acetilcolinesterase para o Tratamento da Doença de

Alzheimer. 2016. Master’s thesis (Master in Chemistry) - Instituto Militar de

Engenharia Instituto Militar de Engenharia ,Coordenação de Aperfeiçoamento de Pessoal

de Nível Superior . Advisor: Jose Daniel Figueroa-Villar.

2015:

1. Fabio de Vasconcellos Fontes. "SínDoctoral thesis e Avaliação Anti T. Cruzi de Novos

Análogos de Benzanidazol". 2015. Master’s thesis (Master in Chemistry) - Instituto

Militar de Engenharia, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.


2014:

215


215

1. Danielle Rodrigues Garcia. "Aplicação de FERMO em Química Medicinal". 2014.

Master’s thesis (Master in Chemistry) - Instituto Militar de Engenharia, . Advisor: Jose

Daniel Figueroa-Villar.

2013:

1. Clara Simões. Estudo da interação de intercalantes radiossensibilizadores em DNA

através da técnica de RMN. 2013. Master’s thesis (Master in Chemistry) - Instituto

Militar de Engenharia .Advisor: Jose Daniel Figueroa-Villar.

AL 06 - Associate Laboratory of Proteins and Proteomic Heterologous Expression

(Coordinator: Hernan Terenzi - UFSC)


2016:

1. Philipe Gabriel. Hidrolases sintéticas. 2016. Master’s thesis (Master in Biochemistry) -

Universidade Federal de Santa Catarina, Advisor: Hernan Francisco Terenzi.

2015:

1. Cristine Saibert. Interação drogas-DNA. 2015. Master’s thesis (Master in Chemistry) -

Universidade Federal de Santa Catarina, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Hernan Francisco Terenzi.

2. Nathalia Castilho. Nucleases e Proteases sintéticas. 2015. Master’s thesis (Master in

Biochemistry) - Universidade Federal de Santa Catarina, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Hernan Francisco Terenzi.

2014:

1. Gabriel Luiz Kreft. Hidrolases sintéticas. 2014. Master’s thesis (Master in Chemistry) -



AL_7- Associated Laboratory of Proteins Biochemistry

(Coodinator: Carlos Henrique Inácio Ramos. UNICAMP)


2016:

1. Izabella Venturini Cagliari. Clonagem, expressão, purificação e caracterização da

proteína SGT1 da cana-de-açúcar, uma co-chaperona do sistema Hsp90. 2016. Master’s

thesis (Master in Chemistry) - Universidade Estadual de Campinas, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Carlos Henrique Inacio Ramos.

Advisor: Carlos Ramos

2015:

1. Ana Luíza Assin Squillace. Master’s thesis. Title: "Expressão, purificação e

caracterização da co-chaperona HOP ('Hsp70-Hsp90 Organizing Protein') de sorgo"

2015. Advisor: Carlos Ramos

2. Daniela Zacharias Cypriano. “Fermentação da biomassa da casca de laranja com

utilização da hidrólise ácida e enzimática”. 2015. Master’s thesis. Química - Universidade

Estadual de Campinas. Advisor: Ljubica Tasic

2014:

1. Bárbara Ramalho Peres. Master’s thesis. Title: "Clonagem, expressão e purificação de

proteínas que participam de um complexo envolvido na mediação da interação entre a

chaperona Hsp90 e complexos DNA- ou RNA-proteína em Leishmania

amazonensis."2014. Advisor: Carlos Ramos

AL 8 - Associated Laboratory of Macromolecules Crystallization

(Coodinator: Marcelo Santos Castilho -UFBA)


216


216

2015:

1. Ayala Ribeiro da Silva. Estudo epidemiológico de candidemia no Hospital Universitário

Prof. Edgard Santos, Salvador, BA. 2015. Dissertation (Mestrado em FARMÁCIA) -

Universidade Federal da Bahia, Fundação de Amparo à Pesquisa do Estado da Bahia.

Advisor: Tânia Fraga Barros.

2014:

1. Bárbara Velame Ferreira Teixeira. Avaliação De Potenciais Inibidores De Pteridina

Redutase 1 (PTR1) e Dihidrofolato Redutase-Timidilato Sintase(DHFR-TS) DE

Leishmania chagasi. 2014. Dissertation (Mestrado em Farmácia) - Universidade Federal

da Bahia, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor:

Marcelo Santos Castilho.

2. Gean Marcelo Costa. Identificação e planejamento de inibidores da enzima Tripanotiona

Redutase de Leishmania braziliensis. 2014. Dissertation (Mestrado em Programa de Pós-

Graduação em Biotecnologia) - Universidade Estadual de Feira de Santana, Coordenação

de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Marcelo Santos Castilho.

3. Renata Souza do Amaral. Detecção e identificação de espécies de Candida em

hemoculturas de um hospital de Salvador, Bahia, através da Reação em Cadeia da

Polimerase em tempo real (RT-PCR).. 2014. Dissertation (Mestrado em Farmácia) -

Universidade Federal da Bahia, Conselho Nacional de Desenvolvimento Científico e

Tecnológico. Advisor: Tânia Fraga Barros.

4. Silvia de Araújo Cruvinel. Avaliação na frequência fúngica em pacientes do Hospital Ana

Nery, Salvador, Bahia.. 2014. Dissertation (Mestrado em Farmácia) - Universidade

Federal da Bahia, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Advisor: Tânia Fraga Barros.

5. Vinícius Medeiros de Magalhães. Avaliação da sensibilidade antifúngica in vitro e da

variabilidade genética de isolados de Candida spp. 2014. Dissertation (Mestrado em

FARMÁCIA) - Universidade Federal da Bahia, Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Advisor: Tânia Fraga Barros.

2013:

1. João Antônio Miranda de Oliveira Souza. Variabilidade genética de Cryptococcus spp.

isolados de praças públicas da cidade do Salvador, Bahia.. 2013. Dissertation (Mestrado

em BIOTECNOLOGIA) - Universidade Federal da Bahia, . Advisor: Tânia Fraga Barros.

2. Lara Maria Brito Cunha Ribeiro. Triagem de inibidores da biossínDoctoral thesis de

estafiloxantina em Staphylococcus aureus. 2013. Dissertation (Mestrado em

Biotecnologia) - Universidade Estadual de Feira de Santana, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Marcelo Santos Castilho.

3. Talita de Jesus Caldas Nunes. Identificação molecular de sorotipos e determinação de

?mating-type? de isolados clínicos de Cryptococcus spp.. 2013. Dissertation (Mestrado

em BIOTECNOLOGIA) - Universidade Federal da Bahia, .Advisor: Tânia Fraga Barros.

4. Thamires Quadros Froes. Triagem virtual e avaliação in vivo de inibidores da

prostaglandina E2 microssomal sintetase -1. 2013. Dissertation (Mestrado em

FARMÁCIA) - Universidade Federal da Bahia, Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Joint supervisor: Marcelo Santos Castilho.

AL 9 - Associated Laboratory of Cellular Ultrastructure Hertha Meyer (Coordinator: Wanderley de Souza -IBCCF/UFRJ)


2015:

1. Aline Araujo Alves. Participação do citoesqueleto de actina e da proteína motora miosina

na endocitose em epimastigotas de Trypanosoma cruzi. 2015. Instituto de Biofísica

Carlos Chagas Filho. Advisora: Narcisa L. Cunha e Silva.

217


217

2. Camila Hubner Costabile Wendt. Análise tridimensional dos mecanismos de captação de

hemoglobina e do processo de biogênese dos cristais de hemozoína em Plasmodium

chabaudi. 2015. Instituto de Biofísica Carlos Chagas Filho. Advisor: Kildare Miranda.

3. Camila Silva Gonçalves. Caracterização morfológica e ultraestrutural dos diferentes

estágios de desenvolvimento do Trypanosoma cruzi (clone Dm28c) durante a

metaciclogênese com enfoque no cinetoplasto. 2015. Instituto de Biofísica Carlos Chagas

Filho. Advisora: Maria Cristina Motta. Co-Advisora: Danielle Pereira Cavalcanti.

4. Gabriela Veras De Moraes. Estudo comparado da infecção da forma bradizoíta de

Toxoplasma gondii da cepa ME-49 em células de linhagem intestinal e fibroblasto. 2015.

Instituto de Biofísica Carlos Chagas Filho. Advisora: Marcia Attias.

5. Rachel de Pinho Rachid. Aperfeiçoamento de metodologias de crioprocessamento de

Plasmodium chabaudi para microscopia eletrônica de transmissão. 2015. Instituto de

Biofísica Carlos Chagas Filho. Advisor: Kildare Miranda.

2014:

1. Ana Carolina Loyola Machado. A influência da bacteria simbiótica no metabolismo

energético do tripanossomatídeo hospedeiro Strigomonas culicis. 2014. Instituto de

Biofísica Carlos Chagas Filho. Advisora: Maria Cristina Motta. Co-Advisor: Antonio

Galina Filho.

2013:

1. Carolina de Lima Alcantara. Caracterização ultraestrutural do complexo citóstoma-

citofaringe de epimastigotas de Trypanosoma cruzi. 2013. Instituto de Biofísica Carlos

Chagas Filho. Advisora: Narcisa L. Cunha e Silva.

2. Débora Rocha Afonso Silva. Estudo comparativo dos efeitos do metronidazol,

hidroxiquinuclidina e miltefosina no crescimento, viabilidade e ultraestrutura de

Trichomonas vaginalis. 2013. Instituto de Biofísica Carlos Chagas Filho. Advisores:

Marlene Benchimol e Wanderley de Souza.

3. Sara Teixeira de Macedo Silva. Avaliação de diferentes inibidores da biossínDoctoral

thesis de esteróis em Leishmania: estudos in vitro e in vivo. 2013. Instituto de Biofísica

Carlos Chagas Filho. Advisora: Juliany Cola Fernandes Rodrigues.


Biological Systems

(Coodinator: Paulo Mascarello Bisch - IBCCF/UFRJ)


2016:

1. CRISTÓVÃO ANTUNES DE LANNA. CARACTERIZAÇÃO GENOTÍPICA,

FENOTÍPICA E DO POTENCIAL PATOGÊNICO DE CEPAS DE Vibrio

parahaemolyticus ISOLADAS NO BRASIL. 2016. Dissertation (Mestrado em Biofisica)

- Instituto de Biofisica Carlos chagas Filho da UFRJ, Coordenação de Aperfeiçoamento

de Pessoal de Nível Superior.Advisor: Wanda Maria Almeida von Kruger.

2015:

1. Daniel Canena Manhães de Carvalho. Estudo comparativo da identificação de células

cervicais em estágios neoplásicos e canceroso por exame de Papanicolaou e por

microscopia de força atômica.. 2015. Dissertation (Mestrado em Ciências Biológicas


de Pessoal de Nível Superior. Advisor: Gilberto Weissmuller.

2014:

1. Allan Amorim Santos. Degradação de microcistina por bactérias presentes no sedimento

da Lagoa de Jacarepaguá RJ. 2014. Dissertation (Mestrado em Ciências Biológicas


Desenvolvimento Científico e Tecnológico. Joint supervisor: Ana Beatriz Furlanetto

Pacheco.

2013:

218


218

1. Iame Alves Guedes. DIVERSIDADE E DINÂMICA DE CIANOBACTÉRIAS E

PRODUÇÃO DE MICROCISTINA NO RESERVATÓRIO DO FUNIL-RJ. 2013.

Dissertation (Mestrado em Ciências Biológicas (Biofísica)) - Universidade Federal do

Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico. Joint

supervisor: Ana Beatriz Furlanetto Pacheco.

AL 11 - Associated Laboratory of Microscopy

(Coordinators: Thais Cristina Baeta Soares Souto Padrón / Ulysses Garcia Casado Lins –

IMPPG/UFRJ)


2016:

1. Clarissa Werneck Ribeiro. Caracterização morfológica e filogenética de procariotos

multicelulares magnetotáticos em ambiente salobro. 2016. Master’s thesis (Master in

Sciences (Microbiology)) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Ulysses Garcia Casado Lins.

2015:

1. Jefferson Bomfim Silva Cypriano. Biomineralização de magnetossomos pela bactéria

magnotática Magnetofaba australis cepa IT-1: fonte de ferro como fator externo de

influência nos defeitos cristalinos. 2015. Universidade Federal do Rio de Janeiro.

Advisor: Ulysses Garcia Casado Lins

2. Pedro Ernesto Lopes Leão. Efeito do sentido do campo magnético na biomineralização de

magnetossomos e sobre a transferência da polaridade magnética na bactéria

magnetotática Magnetovibrio blakemorei. 2015. Master’s thesis. Universidade Federal

do Rio de Janeiro. Advisor: Ulysses Garcia Casado Lins

AL 12 - Associated Laboratory of Cellular Ultrastructure

(Coodinator: Marlene Benchimol – IBCCF/UFRJ and Unigranrio)


2014:

1. Felipe Fernandes da Silva. DESENVOLVIMENTO DE OBJETOS DE

APRENDIZAGEM SOBRE O CICLO DO Plasmodium falciparum NO ENSINO

BÁSICO. 2014. Master’s thesis (Educação em Ciências e Saúde) - Universidade Federal

do Rio de Janeiro- Advisor: Marlene Benchimol

2. Flavia Damiani Gomes. O Ensino de Biologia Celular através de animações. 2014.

Master’s thesis (Ciências Biológicas (Biofísica) - Universidade Federal do Rio de

Janeiro- Advisor: Marlene Benchimol

3. Luiz Carlos dos Santos. Estudo de Trichomonas tenax e suas interações com células de

mamíferos. 2014. Master’s thesis (Ciências Biológicas (Biofísica) - Universidade Federal

do Rio de Janeiro- Advisor: Marlene Benchimol

2013:

1. Débora Rocha. Estudo do Efeito de Drogas que afetam a biossínDoctoral thesis de

esteróis em Trichomonas vaginalis. 2013. Master’s thesis (Ciências Biológicas

(Biofísica)) - Universidade Federal do Rio de Janeiro- Advisor: Marlene Benchimol

AL 13 - Associated Laboratory of Structural Biothecnology

(Coodinator: Celso B. Sant'Anna Filho -INMETRO)


2016:

1. César Silva Xavier. Desenvolvimento e produção de kit didático sobre eletroforese e

estudo de suas aplicações na educação básica, técnica e tecnológica.. 2016. Dissertation

219


219

(Mestrado em Mestrado em Formação Científica para professores) - Universidade Federal


Advisor: Danielle Pereira Cavalcanti.

2. Yuri Komatsu Damas Abud. Contribuição do feixe vascular, parede celular e porção

cristalina da celulose na recalcitrância da cana-de-açúcar. 2016. Master’s thesis - Instituto

Nacional de Metrologia, Qualidade e Tecnologia, Instituto Nacional de Metrologia,

Qualidade e Tecnologia. Advisor: Celso Barbosa de Sant'Anna Filho.

2015:

1. Camila da Silva Gonçalves. Estudo ultraestrutural dos diferentes estágios de

desenvolvimento do Trypanosoma cruzi durante a metaciclogênese com enfoque no

cinetoplasto. 2015. Dissertation (Mestrado em Ciências Biológicas (Biofísica)) -


Científico e Tecnológico. Joint supervisor: Danielle Pereira Cavalcanti.

2. Edgard Gill Bessa. Desenvolvimento de um projeto científico prático em biotecnologia

para alunos do ensino médio. 2015. Master’s thesis - Universidade Federal do Rio de

Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor Celso

Barbosa de Sant'Anna Filho.

3. Lucilene Campos da Hora Silva. O DNA e suas aplicações biotecnológicas: uma análise

da aprendizagem de professores e alunos da educação básica. 2015. Dissertation

(Mestrado em Formação Científica para professores de Biologia) - Universidade Federal


Advisor: Danielle Pereira Cavalcanti.

4. Márcio William da Costa Alves. DESENVOLVIMENTO DE MATERIAL DE

DIVULGAÇÃO SOBRE PROTOZOOSES DE VEICULAÇÃO HÍDRICA. 2015.

Dissertation (Mestrado em Formação Científica para Professores de Biologia) -


Nível Superior. Advisor: Ana Paula Rocha Gadelha.

5. Veronica Silva Ferreia. Produtos biotecnológicos de microalgas: Biodiesel, clorofila e

nanopartículas metálicas. 2015. Master’s thesis - Instituto Nacional de Metrologia,

Qualidade e Tecnologia, . Advisor: Celso Barbosa de Sant'Anna Filho.

2014:

1. Jonas Wendling Coelho Vieira. Processo de criação de um website de pesquisa sobre

protozooses. 2014. Dissertation (Mestrado em Formação Científica para Professores de

Biologia) - Universidade Federal do Rio de Janeiro, Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Advisor: Danielle Pereira Cavalcanti.


(Coordinator: Edilene Oliveira da Silva – UFPA.)


2015:

1. Bruno José Martins da Silva. "Ação imunomoduladora e leishmanicida do extrato aquoso

proveniente da raiz da planta Physalis angulata L. 2015. Master’s thesis. Biologia de

Agentes Infecciosos e Parasitários. Universidade Federal do Pará. Advisor Edilene

Oliveira da Silva.

2. Caroline Martins Almeida. "Estudo da ação imunomodulatoria do Ácido kójico sobre as

células mononucleares da medula óssea de camundongos." 2015. Master’s thesis.

Neurociências e Biologia Celular. Universidade Federal do Pará. Advisor Edilene

Oliveira da Silva.

3. Paula Cristina Rodrigues Frade. "Ação do Ácido Kójico sobre neutrófilos humanos e

durante infecção com Leishmania (Leishmania) amazonensis. 2015. Master’s thesis in

Biologia de Agentes Infecciosos e Parasitários. Universidade Federal do Pará. Advisor

Edilene Oliveira da Silva.

2014:

220


220

1. Lienne Silveira de Moraes. "Ação do alcaloide (+)-filantidina sobre o protozoário

Leishmania (Leishmania) amazonensis e a célula hospedeira". 2014. Master’s thesis.

Neurociências e Biologia Celular. Universidade Federal do Pará. Advisor Edilene

Oliveira da Silva.

2. Rodrigo Ribeiro Furtado. "Detecção da Atividade e Imunolocalização da Enzima Óxido

Nitrico Sintase em Leishmania (Leishmania) amazonensis e Leishmania (Viannia)

braziliensis" 2014. Master’s thesis. Neurociências e Biologia Celular. Universidade

Federal do Pará. Advisor Edilene Oliveira da Silva.

2013:

1. Amanda Anástacia Pinto Hage. "Análise Citoquímica e Ultraestrutural de duas cepas de

Leishmania (V.) braziliensis obtidas em diferentes dias de cultivo In Vitro". 2013.

Master’s thesis. Neurociências e Biologia Celular. Universidade Federal do Pará. Advisor

Edilene Oliveira da Silva.

2. Jorge Augusto Leão Pereira. "Ação do metabólito 5-hidroxi-2-hidroximetil-γ-pirona,

sobre o fungo filamentoso Curvularia pallescens". 2013. Master’s thesis. Biologia de

Agentes Infecciosos e Parasitários. Universidade Federal do Pará. Advisor Edilene

Oliveira da Silva.

3. José Aprigio Nunes Lima. "Avaliação epidemiológica da fauna flebotomínica (Diptera:

Psychodidae) na área de abrangência do Campus II do Instituto Evandro Chagas,

Ananindeua, Estado do Pará, Brasil". 2013. Master’s thesis. Biologia de Agentes

Infecciosos e Parasitários. Universidade Federal do Pará. Advisor Edilene Oliveira da

Silva.

4. Raquel Raick Pereira da Silva. "Estudo in vitro do extrato aquoso de Physalis angulata

sobre o protozoário Leishmania (L.) amazonensis". 2013. Master’s thesis. Neurociências

e Biologia Celular. Universidade Federal do Pará. Advisor Edilene Oliveira da Silva.

AL 15 - Associated Laboratory of Microscopy CETENE (Coodinator: Christina Alves Peixoto - Fundação Oswaldo Cruz)


2015:

1. Ingrid Tavares de Lima. Avaliação dos dietilcarbamazina sobre o processo de inflamação

pulmonar aguda induzida por lipopolissacarídeo. 2015. Dissertation (Mestrado em

Ciências Biológicas) - Universidade Federal de Pernambuco, Fundação de Amparo à

Ciência e Tecnologia do Estado de Pernambuco. Advisor: Christina Alves Peixoto.

2. Maria Eduarda Rocha de França. ANÁLISES DOS EFEITOS DA

DIETILCARBAMAZINA (DEC) SOBRE A FIBROSE HEPÁTICA EM

CAMUNDONGOS C57BL/6J WILD TYPE. 2015. Dissertation (Mestrado em Ciências

Biológicas) - Universidade Federal de Pernambuco, Fundação de Amparao a Pesquisa do

Estado de Pernambuco. Advisor: Christina Alves Peixoto.

3. Shyrlene Meiry da Rocha Araújo. AVALIAÇÃO DOS EFEITOS DO DERIVADO

TIAZOLIDÍNICO LPSF/GQ-02 SOBRE AS VIAS DE SINALIZAÇÃO DO AMPK E

SREBP1 NO METABOLISMO LIPÍDICO HEPÁTICO DE CAMUNDONGOS LDLR-

/-. 2015. Dissertation (Mestrado em Ciências Biológicas) - Universidade Federal de

Pernambuco, Fundação de Amparao a Pesquisa do Estado de Pernambuco. Advisor:


4. Wilma Helena de Oliveira. AVALIAÇÃO DOS EFEITOS DA METFORMINA SOBRE

A NEURODEGENERAÇÃO NO MODELO DE ENCEFALOPATIA DIABÉTICA EM

CAMUNDONGOS C57BL/6. 2015. Dissertation (Mestrado em Ciências Biológicas) -

Universidade Federal de Pernambuco, Coordenação de Aperfeiçoamento de Pessoal de

Nível Superior. Advisor: Christina Alves Peixoto.

2014:

1. Deniele Bezerra Lós. Avaliação da aplicação do exercício aquático precoce no processo

regenerativo do nervo periférico submetido à neurotmese experimental. 2014.

Dissertation (Mestrado em Fisioterapia) - Universidade Federal de Pernambuco,

221


221

Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco. Joint supervisor:


2. Gabriel Barros Rodrigues. AVALIAÇÃO DOS EFEITOS DA DIETILCARBAMAZINA

SOBRE OS MECANISMOS REGULATÓRIOS DA INFLAMAÇÃO HEPÁTICA

INDUZIDA PELO ALCOOLISMO. 2014. Dissertation (Mestrado em Ciências

Biológicas) - Universidade Federal de Pernambuco, Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Advisor: Christina Alves Peixoto.

3. Laise Aline Martins dos Santos. AVALIAÇÃO DOS EFEITOS DA

DIETILCARBAMAZINA SOBRE OS MECANISMOS REGULATÓRIOS DO NF-kβ

NA INFLAMAÇÃO AGUDA PULMONAR EM CAMUNDONGOS. 2014. Dissertation

(Mestrado em Ciências Biológicas) - Universidade Federal de Pernambuco, Fundação de

Amparao a Pesquisa do Estado de Pernambuco. Advisor: Christina Alves Peixoto.

2013:

1. Rayana Leal de Almeida Luna. AVALIAÇÃO DOS EFEITOS DO INIBIDOR DE

FOSFODIESTERASE-5 SOBRE O ÚTERO GRAVÍDICO EM MODELO DE

TROMBOFILIA INDUZIDO POR LIPOPOLISSACARÍDEOS EM

CAMUNDONGOS.. 2013. Dissertation (Mestrado em Ciências Biológicas) -

Universidade Federal de Pernambuco, Coordenação de Aperfeiçoamento de Pessoal de

Nível Superior. Advisor: Christina Alves Peixoto.

AL 16 - Associate Laboratory of Molecular And Cellular Cardiology

(Coordinator: Antonio Campos de Carvalho – IBCCF/UFRJ)


2016:

1. Maria Gabriela de Oliveira Barbeta. Caracterização da matriz extracelular produzida por

cardiomiócitos derivados de células-tronco embrionárias humanas em cultivo

tridimensional. 2016. Master’s thesis (Master's in Biological Sciences (Physiology)) -

Instituto de Biofísica Carlos Chagas Filho, . Advisor: Adriana Bastos Carvalho.

2014:

1. Diorney Luiz Souza Gran da Silva. Influência do tratamento com células-tronco

mesenquimais sobre a função tireoidea de animais com diabetes mellitus tipo 1. 2014.

Master’s thesis (Master's in Biological Sciences (Physiology)) - Universidade Federal do

Rio de Janeiro, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do RJ.

Advisor: Emiliano Horacio Medei.

2. Isalira Peroba Ramos de Góes Freitas. "Avaliação do potencial terapêutico das células

mesenquimais derivadas de tecido adiposona fase aguda da cardiomiopatia chagásica

experimental". 2014. Master’s thesis. Medicina (Radiologia) - UFRJ. Advisor: Regina

Coeli dos Santos Goldenberg.

3. Lanuza Alaby Pinheiro Faccioli. "Avaliação do processo de descelularização hepática e

estudo da utilização dessa matriz na bioengenharia tecidual". 2014. Master’s thesis.

Medicina (Radiologia) - UFRJ. Advisor: Regina Coeli dos Santos Goldenberg.

2013:

1. Bruna Farjun. "Perfil de Expressão de microRNAs no Remodelamento Cardíaco Pós-

Infarto do Miocárdio". 2013. Master’s thesis (Master's in Biological Sciences

(Physiology)) - IBCCF/UFRJ. Advisor: Adriana Bastos Carvalho.

2. Fabiana Bergamin Muccillo. "Caracterização fenotípica e funcional da fração

mononuclear da medula óssea de pacientes com cardiomiopatia chagásica crônica". 2013.

Master’s thesis. Doenças Infecciosas - Fiocruz, Advisor: Antonio Carlos Campos de

Carvalho

3. Grazielle Suhett Dias. "Estabelecimento de um modelo de lesão hepática induzida por

radiação ionizante". 2013. Master’s thesis. Medicina (Radiologia)) - UFRJ. Advisor:

Regina Coeli dos Santos Goldenberg.

222


222

4. Poliana Rodrigues Alves. "Isolamento, cultivo e caracterização de células derivadas de

cardioesferas de camundongos". 2013. Master’s thesis (Master in Health Sciences) -

Universidade Federal de Uberlândia. Co-advisor: Adriana Bastos Carvalho.

5. Raiana Andrade Quintanilha Barbosa. "Análise da expressão de microRNAs em pacientes

com doença isquêmica do coração". 2013. Master’s thesis (Master's in Biological

Sciences (Physiology)) - IBCCF/UFRJ. Advisor: Adriana Bastos Carvalho.

AL 17. Associated Laboratory of Ion transport physiology in health and disease

(Coodinator: Adalberto Ramón Vieyra – IBCCF/UFRJ)


2016:

1. Andreson Charles de Freitas Silva. Albumina modula a Na+-ATPase de túbulo proximal:

Possível papel na excreção renal de sódio. 2016. Dissertation (Mestrado em Ciências

Fisiológicas) - Universidade Estadual do Ceará, Fundação Cearense de Apoio ao

Desenvolvimento Científico e Tecnológico. Advisor: Celso Caruso Neves.

2. Luiz Fernando Carvalho Kelly. Caracterização bioquímica do transporte de fosfato na

ameba de vida livre Acanthamoeba castellani e seu possível papel no processo de

encistamento. 2016. Dissertation (Mestrado em Química Biológica) - Universidade

Federal do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e

Tecnológico. Advisor: Jose Roberto Meyer Fernandes.

2015:

1. Adriana Carvalho Natal de Moraes. Toxicidade renal da cilindrospermopsina em modelo

murino. 2015. Dissertation (Mestrado em Ciências Biológicas (Biofísica)) - Universidade

Federal do Rio de Janeiro. Joint supervisor: Celso Caruso Neves.

2. Dayana de Souza Freire. Efeito de microcistina-LR no transporte renal de sódio e seu

papel na fisiologia renal. 2015. Dissertation (Mestrado em Ciências Biológicas


Desenvolvimento Científico e Tecnológico. Advisor: Jennifer Lowe.

3. Jéssica Alves de Medeiros Araújo. Reprogramação de células do cordão umbilical

humano em neurônios excitatórios e inibitórios. 2015. Dissertation (Mestrado em

NEUROCIÊNCIAS) - Universidade Federal do Rio Grande do Norte, . Advisor: Marcos

Romualdo Costa.

4. Juliane Silva de Farias. Repercussão da inflamação durante a gestação sobre a função

placentária e programação de fibrose renal na vida adulta: possibilidade de prevenção

pelo tratamento com α-tocoferol. 2015. Dissertation (Mestrado em Bioquímica e

Fisiologia) - Universidade Federal de Pernambuco, Fundação de Amparo à Ciência e

Tecnologia do Estado de Pernambuco. Advisor: Ana Durce Oliveira da Paixão. Joint

supervisor: Lecio Duarte Vieira Filho

5. Katarine Ferreira da Silva. Estudos da ação do óleo essencial Croton zehtneri em

alterações renais. 2015. Dissertation (Mestrado em Ciências Fisiológicas) - Universidade

Estadual do Ceará, Advisor: Celso Caruso Neves.

6. Margherita Pomatto. PHENOTIPICAL AND FUNCTIONAL CHARACTERIZATION

OF EXTRACELLULAR VESICLES DERIVED FROM HUMAN MESENCHYMAL

STROMAL/STEM CELLS. 2015. Dissertation (Mestrado em Biotecnologie mediche) -

University of Torino,. Joint advisor: Federica Collino.

7. Nathália Rocco Machado. Modulação da atividade Na+/K+ ATPase por peróxido de

hidrogênio gerado através do heme em Leishmania amazonensis. 2015. Dissertation

(Mestrado em Química Biológica) - Instituto de Bioquímica Médica, Fundação Carlos

Chagas Filho de Amparo à Pesquisa do Estado do RJ. Advisor: Jose Roberto Meyer

Fernandes.

8. Regina Souza Aires. EFEITOS DE UM INIBIDOR PREFERENCIAL DA

CICLOOXIGENASE-2, NIMESULIDA, SOBRE O DESENVOLVIMENTO RENAL

DE RATOS SUBMETIDOS À DESNUTRIÇÃO INTRAUTERINA. 2015. Dissertation

(Mestrado em Inovação Terapêutica) - Universidade Federal de Pernambuco,

223


223

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Ana Durce

Oliveira da Paixão.

9. Thayana Roberta Ferreira de Mattos. Estudo da Homeostasia do Cobre na Expressão e

Secreção da Lipocalina-2 em Células do Túbulo Proximal Renal: Papel das ATPases

Transportadoras ATP7A e ATP7B. 2015. Dissertation (Mestrado em Ciências Biológicas


de Pessoal de Nível Superior. Advisor: Rafael Ramos Hospodar Felippe Valverde.

2014:

1. Andreson Charles de Freitas Silva. Mecanismos de falha da natriurese pressórica no curso

do diabetes experimental. 2014. Dissertation (Mestrado em Ciências Fisiológicas) -

Universidade Estadual do Ceará, . Advisor: Celso Caruso Neves.

2. Anita Leocádio Freitas Mesquita. Modulação da atividade 3'nucleotidásica por

5'nucleotídeos em Leishmania amazonensis. 2014. Dissertation (Mestrado em Química

Biológica) - Instituto de Bioquímica Médica, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Jose Roberto Meyer Fernandes.

3. Geissy Lainny de Lima Araújo. Efeitos da sinalizaçãopor Sonic Hedgehog sobre a

proliferação de células tronco neurais e gliogênese no córtex cerebral em

desenvolvimento. 2014. Dissertation (Mestrado em NEUROCIÊNCIAS) - Universidade

Federal do Rio Grande do Norte, Coordenação de Aperfeiçoamento de Pessoal de Nível

Superior. Advisor: Marcos Romualdo Costa.

4. Julliana Ferreira Sant´Anna. Interação parácrina entre células renais e células estromais

mesenquimais: estudo do papel dos mediadores lipídicos. 2014. Dissertation (Mestrado

em Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Marcelo

Einicker Lamas.

5. Luiz Carlos Simas Pereira Junior. Avaliação das atividades (Na+/K+)-ATPásicas de

origem cerebral e renal de camundongos inoculados com veneno da serpente Bothrops

jararaca sobre. 2014. Dissertation (Mestrado em CIÊNCIAS E BIOTECNOLOGIA) -

Universidade Federal Fluminense, Conselho Nacional de Desenvolvimento Científico e

Tecnológico. Advisor: Luiz Roberto Leão Ferreira.

6. Luiza Helena Daltro Cardoso. Envolvimento da proteína cinase C épsilon (PKCe) na

regulação da atividade da Cu(I)-ATPase presente em fígado de porco (Atp7b).. 2014.

Dissertation (Mestrado em Ciências Biológicas (Biofísica)) - Universidade Federal do

Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Advisor: Jennifer Lowe. 7. Paula Mattos. Uso de células mononucleares derivadas de medula óssea (CDMO) em

modelo de isquemia/reperfusão renal provoca alterações na sínDoctoral thesis e na ação

do ácido lisofosfatídico (LPA). 2014. Dissertation (Mestrado em Ciências Biológicas


de Pessoal de Nível Superior. Advisor: Marcelo Einicker Lamas.

2013:

1. Clemilson Berto Jr. Avaliação do potencial teratogênico dos protótipos LASSBio 596 e

LASSBio 468, candidatos a fármacos antiasmáticos. 2013. Dissertation (Mestrado em

Mestrado em Farmacologia e Química Medicinal) - Universidade Federal do Rio de

Janeiro. Joint supervisor: Aloa Machado de Souza.

2. Daianna Rosse Martins Gonçalves. Repercussão do α-tocoferol sobre o stress oxidativo e

angiogênese na placenta de ratas submetidas à desnutrição. 2013. Dissertation (Mestrado

em Bioquímica e Fisiologia) - Universidade Federal de Pernambuco, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Ana Durce Oliveira da

Paixão.

3. Hermany Munguba Vieira. Indicadores de calcio e de voltagem codificados

geneticamente na detecҫao de potenciais de aҫao e inputs sinapticos em cultura de

neuronios hipocampais. 2013. Dissertation (Mestrado em NEUROCIÊNCIAS) -

Universidade Federal do Rio Grande do Norte, Coordenação de Aperfeiçoamento de

Pessoal de Nível Superior. Joint supervisor: Marcos Romualdo Costa.

224


224

4. Luís Paulo N. C. Borges. PAPEL DO ESTRESSE OXIDATIVO HIPOTALÂMICO NA

HIPERTENSÃO INDUZIDA PELA RESTRIÇÃO DIETÉTICA MATERNA. 2013.

Dissertation (Mestrado em Bioquímica e Fisiologia) - Universidade Federal de

Pernambuco, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor:

Ana Durce Oliveira da Paixão.

5. Natalie Emanuelle Ribeiro e Silva. Repercussão do α-tocoferol sobre o stress oxidativo e

angiogênese na placenta de ratas submetidas à sobrecarga de Sódio. 2013. Dissertation

(Mestrado em Ciência Animal Tropical) - Universidade Federal Rural de Pernambuco,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint supervisor: Ana

Durce Oliveira da Paixão.

6. Sabrina Ribeiro Gonsalez. Papel do ácido lisofosfatídico na lesão por isquemia-

reperfusão renal em ratos: ações na atividade dos transportadores de Na+ e na primeira

etapa de ativação do estresse do retículo endoplasmático. 2013. Dissertation (Mestrado

em Farmacologia e Química Medicinal) - Universidade Federal do Rio de Janeiro,

Conselho Nacional de Desenvolvimento Científico e Tecnológico. Joint supervisor:

Marcelo Einicker Lamas. 7. Thayana Roberta Ferreira de Mattos. Estudo da homeostasia do cobre na expressão e

secreção de lipocalina-2: papel das ATPases transportadoras de cobre ATP7A e ATP7B

nos processos de progressão e reparo da lesão renal. 2013. Dissertation (Mestrado em

Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro, Coordenação

de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Marcelo Einicker Lamas.

8. Thiago Pereira da Silva. Correlação entre malária grave e lesão renal em modelo murino.

2013. Dissertation (Mestrado em Ciências Biológicas (Fisiologia)) - Universidade Federal


Advisor: Ana Acacia Pinheiro Caruso Neves and Joint supervisor: Celso Caruso

Neves.


(Coodinated by Prof. Julio Scharfstein- IBCCF/UFRJ)


2015:

1. Lucas Vellasco de Mattos. "O Eixo Mastócito-Calicreína-Cinina: Envolvimento da via

de Contato da Coagulação na Inflamação Edematogênica Induzida por Trypanosoma

cruzi" 2015.Doctoral thesis de Mestrado em Ciências Biológicas- Universidade Federal

do Rio de Janeiro- IBCCFº, Advisor: Julio Scharfstein

2. Rafaela Rangel Serra. "Microscopia Intravital: Padronização da Aplicação Tópica no

Modelo da Bolsa da Bochecha do Hamster" 2015. Doctoral thesis de Mestrado em

Formação Técnica para Pesquisa Biomédica- Universidade federal do rio de Janeiro-

IBCCFº, Advisor: Robson Coutinho-Silva, Erik Svensjö, Julio Scharfstein

AL 19 - Associated Laboratory of Cellular and Molecular Neurology

(Coordinator: Rosalia Mendez Otero)

Total of X5dissertations completed during the whole period, as follows:

2016:

1. Igor Bonacossa Pereira. Avaliação funcional e histológica do nervo isquiático após lesão

por esmagamento em modelo animal de esclerose lateral amiotrófica. 2016. Dissertation

(Mestrado em Ciências Biológicas (Biofísica)) - Universidade Federal do Rio de Janeiro,

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Rosalia

Mendez-Otero.

2. Teresa Puig Pijuan. AVALIAÇÃO DO EFEITO NEUROPROTETOR DAS CÉLULAS

MESENQUIMAIS DE GELEIA DE WHARTON EM UM MODELO DE ESTRESSE

OXIDATIVO EM CÉLULAS NEURAIS. 2016. Dissertation (Mestrado em Ciências

225


225

Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro, Coordenação de

Aperfeiçoamento de Pessoal de Nível Superior. Advisor: Rosalia Mendez-Otero.

3. Victor Bodart Santos. Caracterização de vesículas extracelulares derivadas de células-

tronco mesenuimais da geléia de Wharton e seu potencial neuroprotetor em um modelo in

vitro da Doença de Alzheimer. 2016. Dissertation (Mestrado em Ciências Biológicas


Desenvolvimento Científico e Tecnológico. Advisor: Rosalia Mendez-Otero.

2014:

1. Alvaro Carrier Ruiz. Interacao entre celulas mesenuimais de medula ossea e filamentos

de policaprolactona para regeneracao de nervos perifericos. 2014. Dissertation (Mestrado

em Ciências Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Rosalia Mendez-Otero.

2013:

1. Almir Jordão da Silva Junior. Potencial regenerativo de células-tronco mesenquimais em

modelo de lesão no nervo óptico. 2013. Dissertation (Mestrado em Ciências Biológicas

(Biofísica)) - Universidade Federal do Rio de Janeiro, . Advisor: Rosalia Mendez-Otero.

AL 20. Associated Laboratory of Inflammation and Metabolism

(Coordinator: Fernando Augusto Bozza)


2016:

1. Caroline Mendes Ferreira. Efeitos fisiologicos da interferencia da cristalizacao de heme

no inseto triatomineo Rhodnius prolixus. 2016. Dissertation (Mestrado em Ciencias

Biologicas Modalidade Medica) - Universidade Federal do Rio de Janeiro, Conselho

Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Marcus Fernandes de

Oliveira.

2. Hugo Boechat. Avaliação do perfil epidemiológico e gravidade de pacientes infectados

pelo vírus HIV internados na terapia intensiva. 2016. Dissertation (Mestrado em Pesquisa

Clinica em Doenças Infecciosas) - Fundação Oswaldo Cruz, . Advisor: Fernando Augusto

Bozza.

3. Jorge André Marques Bravo. Analise da distribuição espacial e capacidade instalada de

leitos de cuidados intensivos no Estado do Rio de Janeiro frente à carga de doença

infecciosa aguda: Preparação para o enfrentamento de pandemias. 2016. Dissertation

(Mestrado em Pesquisa Clinica em Doenças Infecciosas) - Fundação Oswaldo Cruz, .

Advisor: Fernando Augusto Bozza.

4. Luciana Domett Siqueira. Estudo dos mecanismos de deficit cognitivo associado ao

envelheciment: o papel da inflamação sistêmica. 2016. Dissertation (Mestrado em


Desenvolvimento Científico e Tecnológico. Advisor: Fernando Augusto Bozza.

2015:

1. Ana Paula Mendonça Miranda. Estudos sobre as alterações funcionais em mitocôndrias

de células do sistema nervoso central disparadas por produtos derivados do sangue. 2015.


Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Marcus

Fernandes de Oliveira.

2. Edwiges Motta. Diagnóstico de infecções fúngicas em pacientes sida/hiv internados na

terapia intensiva. 2015. Dissertation (Mestrado em Pesquisa Clinica em Doenças

Infecciosas) - Fundação Oswaldo Cruz, . Advisor: Fernando Augusto Bozza.

3. Luciana Magalhães Leo. Papel da Lipoxina A4 na fisiologia do sistema nervoso central e

no dano cognitivo associado á neuroinflamação.. 2015. Dissertation (Mestrado em


Desenvolvimento Científico e Tecnológico. Advisor: Fernando Augusto Bozza.

4. Luiz Felipe Garcia de Souza. Estudos sobre as alterações funcionais em mitocôndrias de

plaquetas disparadas por produtos derivados do sangue. 2015. Dissertation (Mestrado em

226


226

quimica biologica) - Universidade federal do rio de janeiro, . Advisor: Marcus Fernandes

de Oliveira.

5. NATHALIA FERREIRA COSTA. AVALIAÇÃO DA Atividade Farmacologica do oleo

essencial de Piter rivinoides e Kunth. 2015. Dissertation (Mestrado em Biologia Celular e

Molecular) - Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico

e Tecnológico. Advisor: Hugo Caire de Castro Faria Neto.

2014:

1. Debora Alves Caldeira dos Santos Amorim. Estudo da Neuriinflamatórios do uso de

medicações anestésicas e sedativos na Sepse. 2014. Dissertation (Mestrado em Biologia

Celular e Molecular) - Fundação Oswaldo Cruz, . Advisor: Hugo Caire de Castro Faria

Neto.

2. Debora Alves Caldeira dos Santos Amorim.. Estudo da Neurotoxidade de drogas

anestésicas e sedativos na Sepse.. 2014. Dissertation (Mestrado em Biologia Celular e

Molecular) - Fundação Oswaldo Cruz, . Advisor: Fernando Augusto Bozza.

3. Diego de Faria Magalhães Torres. Capacidade Física e Qualidade de Vida de Pacientes

com Hipertensão Pulmonar Grupos I e IV. 2014. Dissertation (Mestrado em Clínica

Médica) - Universidade Federal do Rio de Janeiro, . Advisor: Walter Araujo Zin.

4. Liliana Guerrero Ayala. EFEITOS DA SEDAÇÃO E BLOQUEIO NEUROMUSCULAR

EM RATOS COM SÍNDROME DO DESCONFORTO RESPIRATÓRIO AGUDO.

2014. Dissertation (Mestrado em Engenharia Biomédica) - Universidade Federal do Rio

de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Joint

supervisor: Antonio Giannella Neto.

5. Patricia Piazza Rafful. Avaliação de Concordância entre a Ressonância Magnética e a

Tomografia Computadorizada no Estudo do Parênquima Pulmonar. 2014. Dissertation

(Mestrado em Radiologia) - Universidade Federal do Rio de Janeiro, . Advisor: Rosana

Souza Rodrigues.

6. Rhenan Bartels Ferreira. Estimativa do Limiar Anaeróbio a partir do Ponto de Inflexão da

Frequência Cardíaca Durante Teste Progressivo Máximo. 2014. Dissertation (Mestrado

em Engenharia Biomédica) - Universidade Federal do Rio de Janeiro, Conselho Nacional

de Desenvolvimento Científico e Tecnológico. Joint supervisor: Antonio Giannella Neto.

7. Viviane Mancin. Ventilação Variável e Ventilação Variável em Burst: Impactos na

Estrutura e Função Pulmonar. 2014. Dissertation (Mestrado em Programa de Fisiologia e

Biofísica Celular) - Instituto de Biofísica Carlos Chagas Filho-UFRJ, . Advisor: Alysson

Roncally Silva Carvalho.

2013:

1. Carolina Pesce Lamas Constantino. Avaliação da Enterografia por Ressonância

Magnética na Doença de Crohn.. 2013. Dissertation (Mestrado em Radiologia) -

Universidade Federal do Rio de Janeiro, . Advisor: Rosana Souza Rodrigues.

2. Emersom Cicilini Mesquita. Avaliação da função plaquetária na infecção pelo HIV. 2013.

Dissertation (Mestrado em Pesquisa Clinica em Doenças Infecciosas) - Fundação

Oswaldo Cruz, . Advisor: Fernando Augusto Bozza.

3. Liliana Guerrero Ayala. Contusão pulmonar por trauma torácico: Caracterização das

alterações na estrutura e função pulmonar por Tomografia por Emissão de Pósitrons em

Ratos. 2013. Dissertation (Mestrado em Engenharia Biomédica) - Universidade Federal


Advisor: Alysson Roncally Silva Carvalho.

4. Luiggi Araujo Lustosa. Monitorização não invasiva da frequência respiratória por método

optoeletrônico. 2013. Dissertation (Mestrado em Engenharia Biomédica) - Universidade


Superior. Joint supervisor: Antonio Giannella Neto.

5. Luis Felipe Santos da Cruz Paula. COPARAÇÃO ENTRE A ESTIMATIVA DA

DISTENSIBILIDADE PULMONAR REGIONAL A PARTIR DE IMAGENS DE

TOMOGRAFIA COMPUTADORIZADA E PROPRIEDADES ELÁSTICAS DO

SISTEMA RESPIRATÓRIO EM PULMÕES SAUDÁVEIS. 2013. Dissertation

(Mestrado em Ciências Biológicas (Fisiologia)) - Universidade Federal do Rio de Janeiro,

227


227

Conselho Nacional de Desenvolvimento Científico e Tecnológico. Advisor: Alysson

Roncally Silva Carvalho.

6. Raquel Rodrigues Barbieri. Diagnóstico da Hanseníase com Lesões Únicas. 2013.

Dissertation (Mestrado em Pesquisa Clinica em Doenças Infecciosas) - Fundação

Oswaldo Cruz, . Advisor: Fernando Augusto Bozza.

7. Rhenan Bartels Ferreira. Estimativa dos limiares do exercício proressivo máximo a partir

da frequência cardíaca como índice preditivo do nível de treinamento e condicionamento

respiratório. 2013. Dissertation (Mestrado em Engenharia Biomédica) - Universidade

Federal do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e

Tecnológico. Advisor: Alysson Roncally Silva Carvalho.

8. Roberta Faria Lemos. Avaliação dos pacietes com hanseníase multibacilar submetidos a

esquema terapêutico substutivo. 2013. Dissertation (Mestrado em Pesquisa Clinica em

Doenças Infecciosas) - Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento

Científico e Tecnológico. Advisor: Fernando Augusto Bozza.

9. Viviane Brandão Amorim. Aspectos Tomográficos da Infecção por H1N1. 2013.

Dissertation (Mestrado em Medicina (Radiologia)) - Universidade Federal do Rio de

Janeiro, . Advisor: Rosana Souza Rodrigues.

228


228

Science education and outreach activities

229


229

Science Education and Outreach

The National Institute for Structural Biology and Bioimage (INBEB) is not only a a

reference center for biomedical and biotechnological research in Latin America, it also plays a

role in education and popularization of science. To improve INBEB’s reach beyond academia, we established in 2012 the Center for

Education and Science Communication (NEDiCi, in the Portuguese acronym). Its main goals

are to disseminate the scientific results from our groups to the general public, as well as to

promote activities (courses, lectures, workshops, tours, videos and others) designed for teachers

and students from primary and secondary schools. The NEDiCi is currently coordinated by researcher Patricia S. dos Santos (AL 1 -

UFRJ), who has extensive experience in organizing courses for grade school students, and

teachers, and for undergraduates. Since 1996, Dr Santos participates in teaching summer

courses offered by the Institute of Medical Biochemistry at UFRJ and is currently developing a

project to assess the creativity and learning of students participating in activities organized by

NEDiCi. The Center also benefits from the collaboration of other INBEB researchers, among

them Professor Emiliano Medei (from AL 16, and IBCCF/UFRJ), who had two projects in

science education and outreach approved by FAPERJ that are developed in partnership with

INBEB, and Professor Edilene Oliveira da Silva (AL 14 - UFPA), who promotes and

participates in several scientific events, science fairs, and summer workshops, actively

collaborating for the dissemination and popularization of science in Northern Brazil. The scientific journalist Marina Verjovsky contributes to such communication efforts,

keeping an updated web presence, as well as dealing with the national media and working as

public relations.

230


230

The following offer more details of some of the activities supported, sponsored and/or

developed by the Center:

Pint of Science!

May – 2016

The Pint of Science festival aims to deliver interesting and relevant talks on the latest

science research in an accessible format to the public – all in the pub! It is a platform which

allows people to discuss research with the people who carry it out - no prior knowledge of the

subject is required. It is run mainly by volunteers and was established by a community of

postgraduate and postdoctoral researchers in 2012. The main festival takes place annually over

three days in the month of May simultaneously in pubs of more than 100 cities in 12 countries

around the world. Pint of Science is a non-profit organisation.

In the 2016 edition, the coordinator of INBEB, Jerson Lima, spoke about the Zika virus

in Ernesto's Bar, in Lapa. The next day, the researcher Fernanda Tovar-Moll spoke on the theme

"Technologies reconfiguring our brain", in the Cultural Space Olho da Rua, in the neighborhood

of Botafogo.

Lectures in public schools.

September - 2015

Professor Julio Scharfstein (UFRJ), coordinator of AL 18, spoke about the history of

immunology and vaccines for youngsters of the 3rd year (from a technical course in

biotechnology) at the Círculo Operário State High School, in Xerém, Duque de Caxias.

Meeting of students with a Nobel of chemistry at the Science Museum

July - 2014

The scientist Kurt Wüthrich, Nobel laureate in Chemistry 2002 and associate fellow of

INBEB since 2012, participated in a chat with high school students promoted by the Museum of

Science and Life of the municipality of Duque de Caxias, in Rio de Janeiro. According to

Wüthrich, although he has given numerous lectures and conferences around the world, both

before and after receiving the Nobel Prize, this was the first time he had the opportunity to

speak to high school students.

At the meeting, he sought to inspire the young people: "Look for something that is fun

for you, as well as hard work and hard work. Enjoing work is the best way to get good results in

whatever field you choose."

Inaugural Lecture at the Center of Health Sciences of UFRJ by Prof. Jerson Lima

August - 2013

231


231

The dean of the Health Sciences Center, Prof. Maria Fernanda Quintela, invited the new

students of the Health Sciences Center for an inaugural lecture of welcome, given by Prof.

Jerson Lima da Silva, coordinator of INBEB, under the title "Would cancer be a prion disease?",

Which took place on August 21 at the Auditorium Professor Rodolpho Paulo Rocco. The lecture

was followed by a musical guest, a string duet.

- Science fairs:

Science Fair, Innovation and Technology from Igarapé-Miri (FEICITI):

October - 2015

Popularization of science in Pará Amazon for elementary school, high school

students and undergraduate students. Considered the biggest scientific fair of the region,

happened with the collaboration of the group of Professor Edilene Oliveira da Silva (AL 14 -

UFPA).

232


232

Science fair, Innovation and Technology in the Igarapé-Miri (FEICITI). The FEICITI brought together works from different areas of knowledge. B - Open Science event; A, C-F- Exposition of research projects.

Poster of Sience Fair, Innovation and Technology in the Igarapé-Miri (FEICITI).

Science Caravan

September - 2015

The scientific event occurred in the rural area of the municipality of Igarapé –

Miri (Pará State). The event had robotics exposition, simulation of launching rocket

project, lectures and biological demonstrations. It promotes the democratization and

popularization of science in the riverside community, thus encouraging the participation of these

communities in actions related to Science and Technology.

233


233

A-C: students in the event. D- Researchers from SEMED and UFPA, coordinators of the event.

Science goes to square

August - 2015

Organized by the Municipal Igarapé-Miri Education in partnership with collaboration

and support from the group of Professor Edilene Oliveira da Silva (AL 14 - UFPA). It is an

event focused on the development of science and technology in the municipality of Igarapé-

Miri, seeking to strengthen knowledge and education, and to bring the whole of Miri's society

closer to scientific knowledge. It has exhibitions, experiments, demonstrations and lots of fun

for the whole family, in the central square of the municipality.

234


234

Event Science Goes to Square . Scientific event in the biggest square at the city of

Igarapé-Miri (Pará State).

VII Science fair Manoel Antônio de Castro

December - 2014

Science, technology and innovation as a proposal for popularization of science in Pará

Amazon. With the collaboration of the group of Professor Edilene Oliveira da Silva (AL 14 -

UFPA).

VI Science fair Manoel Antônio de Castro

December - 2013

Science and citizenship: new directions, new achievements in Pará Amazon. With the

collaboration of the group of Professor Edilene Oliveira da Silva (AL 14 - UFPA).

3rd Faperj science fair

October – 2013

INBEB participated in the 3rd FAPERJ Fair on Science, Technology and Innovation

which took place in October 10, 11 and 12, 2013, in Rio de Janeiro. At the INBEB stand, the

235


235

public was invited to observe protozoa under an optical microscope. We also presented the

printed and audiovisual materials produced by our INCT, as well as posters about the scientific

dissemination and education projects developed by our groups.

On the last day of the event, the INBEB coordinator, Jerson Lima da Silva, participated

as a coordinator of a round table on new ways of disseminating science in the media, which

included journalists Elisa Oswaldo-Cruz Marinho (ABC communication advisor), Ana Lúcia

Azevedo (O Globo newspaper), Bernardo Esteves (Piauí magazine) and Alícia Ivanissevich

(Ciência Hoje magazine).

Participants attending the INBEB booth

From left to right: Elisa Oswaldo-Cruz Marinho (ABC communication advisor), Ana Lúcia Azevedo (O Globo newspaper), Jerson Lima da Silva, Bernardo Esteves (Piauí magazine) and Alícia Ivanissevich (Ciência Hoje magazine).

Expo-sciences International Abu Dhabi / United Arab Emirates (ESI WORLD)

September 2013

Professor Edilene Oliveira da Silva’s group (AL 14 - UFPA) also participated in this

international science fair, along with students from Pará, Northern Brazil.

- Vacation (winter and summer) workshops

236


236

The researcher Patrícia Souza dos Santos (from AL1) coordinates the INBEB winter

and summer courses, which are held in the university laboratories. They are aimed at teachers of

Basic Education (of any discipline); Undergraduate students (of any specialty); High school

students (1st, 2nd and 3rd grade) and primary school students (8th and 9th grade). Those

participants spend a week asking questions and conducting experiments in search of their

answers, like true scientists. The workshops are entirely free, with lunch and certificate

included.

School students participating from a course.

The latest editions of the workshops were:

Workshop on “Mosquito: science and myth”

January 2016

The extension superintendent at UFRJ, Prof. Ana Inês de Sousa, welcomed the 50

participating students of this workshop coordinated by Patricia Souza dos Santos (AL 1- UFRJ).

With a crowded laboratory, the aspiring scientists uncovered the mysteries of mosquitoes, which

constitute an important Brazilian public health issue and more so especially in Rio de Janeiro.

237


237

Poster from the latest workshop

“Mosquito: science and myth”

July 2015:

The workshop was coordinated by Patricia Souza dos Santos (AL 1- UFRJ).

“Food: in health and illness”

January 2014

Workshop coordinated by Patricia Souza dos Santos (AL 1- UFRJ).

“Mosquito: science and myth”

January 2014

Workshop coordinated by Patricia Souza dos Santos (AL 1- UFRJ).

"Food: in sickness and in health"

January 2013:

Taught at UFRJ for 14 school students and 10 teachers. It was coordinated by Patricia

Souza dos Santos (AL 1- UFRJ).

"Mosquitoes: Science and Myth"

January 2013:

238


238

Taught at UFRJ for 15 school students and 14 teachers. It was coordinated by Patricia

Souza dos Santos (AL 1- UFRJ).

"Science and gastronomy: are birds of a feather (and flock together)?"

January 2013:

Special Course for eight high school students who have already done some vacation

course before (Collaboration NEDiCi / INBEB with the Institute of Nutrition Josué de Castro,

UFRJ).

“What do ‘ver-o-peso’ has to do with health?”

January 2013:

Workshop helded in Igarapé-Miri, Pará, coordinated by the group of Professor Edilene

Oliveira da Silva (AL 14 - UFPA).

- INBEB’s partner school wins scientific award

A group of students from State High School Manoel Antônio de Castro (EEMAC),

located in the municipality of Igarapé-Miri in Pará, won the 1st prize in the Health Sciences

category at the event MILSET National (Movement for International Scientific and Technical

Recreation), held in the city of Fortaleza. Among the projects with the highest overall score of

the meeting, the students gained credentials to participate in the international version of the

event, which occured in September 2013 in Abu Dhabi, United Arab Emirates. The awarded paper is entitled "Natural cream for hand hygiene: using biodiversity of the

Amazon to take care of our health" is developed by Mayra Carolina Oliveira and Janaina Santos,

both of the 3rd year of high school, and guided by teachers Josineide Pantoja and Hélio Júnior. The

project investigated the microbicidal action of 13 Amazonian plants, in order to obtain a natural

cream for sanitizing hands, with an effect similar to alcohol. The cream is already being tested

in vitro and will be tested in vivo with mice, in a cooperation with a lab at the Federal

University of Pará (UFPA). This is just one among several achievements by those students, as a result of the teachers

efforts, especially by Josineide Pantoja, who is also a PhD student at the Structural Biology and

Parasitology Program at UFPA. Thus, the school established a partnership with the Associate

Laboratory 14 of INBEB, coordinated by professor Edilene Oliveira da Silva, a researcher at

UFPA and head of the Structural Biology and Parasitology Laboratory in that institution. In addition, four students from the school were invited to participate in the IV INBEB

Annual Meeting, held in April 2013, where they presented their scientific work, along with

239


239

undergraduates, masters and doctorate from various Brazilian states. As a result, INBEB funded

two airline tickets for participation in national conferences. “I thank the whole INBEB team in the person of Dr. Jerson Lima Silva for all your

commitment deposited in Basic Education students, not only from Pará, but throughout Brazil. I

reiterate that every encouragement INBEB gave to our students has been of fundamental

importance for every achievement that we are having in Scientific Initiation”, thanked Pantoja.

- Adoption of a public school

The professor Emiliano Medei (AL 16 - IBCCF/UFRJ) received FAPERJ grants

destined to the Dissemination and Popularization of Science and Support for Public Schools of

Rio de Janeiro. In these projects, the multidisciplinary team promotes interactions among

scientists and high school students from public schools located about 180km from the Federal

University of Rio de Janeiro, in São Pedro da Serra, Municipio de Friburgo – Rio de Janeiro.

The projects bring these students to visit research laboratories at the Federal University of Rio

de Janeiro, where they can observe how some equipment and techniques are used to answer

scientific questions. The project also leads scientists to the school in Friburgo, where they

contributed to the construction of a teaching laboratory in 2011 and a library in mid-2016.

Founded on July 16, 2016, the library was named Marion Villas Boas Sá Rego, in honor of a

writer, journalist and pedagogue who contributed directly to that school in the 1980s. In 1986, she and her

daughter Virginia Villas Boas Sá Rego were responsible for implementing high school education there,

which until then only offered elementary education. Since the beginning of Emiliano's partnership, the

school has been gradually increasing its score in the national assessment of the Basic Education

Development Index (Indeb), rising from 5.4 in 2011 to 6.4 in the last evaluation - well above the average

o of Nova Friburgo (4.3) and even more so if compared to the national average of public schools (3.5).

Students experimenting at the laboratory at the Jose Martins da Costa state school, San Pedro da Serra, RJ.

240


240

From left to right: Marion Villas Boas (with his grandson); Professor Emiliano Medei; Gleici Heringer, pedagogical coordinator of the project and Virginia Villas Boas, a former high school teacher and daughter of Marion .

Other initiatives from INBEB members

- Audiovisual productions

Professors Marlene Benchimol (AL 12) and Wanderley de Souza (AL9) are actively

involved in the production of various didactic and audiovisual materials for scientific

dissemination. They have already produced several interactive media products to teach the life

cycle of Trypanosoma cruzi and Leishmania. Furthermore, they develop some printed materials

containing updated color schemes, animated models, and CDs with 3D animations about the life

cycle of these protozoan parasites. The materials also address issues about developmental stages

in the different hosts, as well as their organelles and specific structures. Those are powerful

tools to help students and teachers understand these themes, as well as the general public. Three

books in Portuguese were already published, about the T. cruzi life cycle, in 2012, other on

Leishmania, published in 2013, and the other on Plasmodium, in 2014. These books are being

distributed free of charge, mainly in public schools and universities.

241


241

Some snapshots from the videos

Those videos have extraordinary visual and didactic quality and are also available at the

INBEB Youtube channel (www.youtube.com/videosinbeb) and at the INBEB website

(www.inbeb.org.br, in the main menu “Audiovisual productions”).

-Educational books

For the AL 7 (of Proteins Biochemistry, coodinated by Professor Carlos Henrique Inácio Ramos,

from UNICAMP), the most important results in education and dissemination of science was the

publication of three book chapters in our research area, the study of molecular chaperones and the tools

used to the study of these proteins. Two chapters in English and one in Portuguese were published.

These chapters have made a detailed review of the structure and function of molecular

chaperones and the importance of these macromolecules for maintaining protein homeostasis.

Addictionally, it was added to each chapter detailed information on molecular biophysical tools for the

study of protein conformation in solution and also on the interaction between proteins and between these

and ligands. Moreover, the chapter have been designed with the objective of spreading the basic

information on the molecular biophysics to the study of proteins.


242


242

INBEB website and social media

The science journalist Marina Verjovsky works in collaboration with NEDiCi on

education projects and establishing a bridge between researchers and society through

dissemination of INBEB activities on the website, social media and the press.

Since 2012, the new INBEB website (www.inbeb.org.br) became more attractive and

dynamic, allowing the public easy access to INBEB information and reports on its

infrastructure. Furthermore, the researchers and collaborators are now able to register their

projects and schedule studies in CENABIO units through the website.

INBEB’s new homepage. See at: www.inbeb.org.br

INBEB is also on Facebook, interacting directly with its audience.

INBEB’s Facebook page. See at:

WWW.FACEBOOK.COM/PAGES/INBEB/128028600698542


243


243

Perspectives and future developments

244


244

The Jiri Jonas National Center for Nuclear Magnetic resonance, inaugurated in 1996,

was the milestone for the National Center for Structural Biology and Bioimaging –

INBEB/CENABIO/UFRJ Among other form of support and sponsorship, the participation in

the Millenium Institute Program as a Millennium Institute for Structural Biology,

Biotechnology and Biomedicine was crucial to consolidate a national facility in NMR, with

three state-of-the-art NMR instruments (400, 600, 800 and a new 900 MHz) and two

instruments for solid-state NMR (500 and 700 MHz).

In the last years, with the support of the National Institute Program, the INCT for

Structural Biology and Bioimaging has been consolidated by creating two more units, one

dedicated to biomaging of small animals (INBEB/CENABIO/UFRJ-2) and the other in

microscopy (INBEB/CENABIO/UFRJ-3). The bioimaging facility has instruments that are at

the forefront of knowledge in this field, some of them the only ones in Latin America, such as 7

Tesla MRI, besides PET/CT/ SPECT, ultrasound and in-vivo high resolution

luminescence/fluorescence animal unit. The microscopy facility now hosts several equipment

for electronic, confocal, multiphoton, and atomic force microscopy. With this, we create the

largest and most advanced collection of equipment in Latin America for NMR of

macromolecules, imaging of small animals and microscopy, within the three Units

accommodated in a total area of 2,200 m2.

Furthermore, as a result of the vigorous activity developed by INBEB members, on

February 28, 2013, INBEB / CENABIO was recognized as a new Supplementary Organ in the

organizational scheme of UFRJ, namely the Nucleus of Structural Biology and Bioimagem

(CENABIO-UFRJ), associated to the Center of Health Sciences. This institutional recognition

confirms the relevance of the research and teaching activities carried out over the INBEB’s

eight years so far, and point to new possibilities for growth and expansion, now as an

independent unit in the organizational structure of UFRJ.

All this infrastructure has increased interaction both among INBEB researchers and

other researchers from different Brazilian and international institutes, including the INCTs.

Gradually, we have also strengthened our ties with IDOR (Instituto D´Or for Research and

Teaching), thereby closing a gap between basic and clinical research (translational research).

The clustering of independent research groups into a National Institute for Science and

Technology has made it possible to create synergistic and increasingly productive interactions.

The catalytic effect of having formal collaborations among the different Associate Laboratories

has been mutually beneficial, leading to synergistic actions that combine structural, dynamics,

molecular biology, and micro-and macro-imaging techniques. During all these years we have

promoted a multidisciplinary program to approach a great number of relevant scientific

questions, as can be seen in our reports.

245


245

One of the main goals of INBEB is to support young professors as they build up their

own research groups. Several publications and thesis dissertations have incorporated a great

number of approaches in the frontier technologies of structural biology, cell biology and

bioimaging, as well in some cases translational medicine. The training of undergraduate and

graduate students as well as post-docs is crucial to produce high-quality science with

publications in high-impact journals. We believe that the following comments, which we have

received from Professor Edilene Oliveira da Silva (coordinator of AL 14 – ICB/UFPA),

summarize much of this success:

"Considering the geographic and scientific isolation of the LA 14, INBEB's support favored a

technical-scientific advance, representing a qualitative and quantitative leap in personnel

training and publications in journals of international circulation. In addition, it favored an

expressive participation of the LA 14 members in activities of education and dissemination of

science in the basic education of students from poor municipalities of the Amazon region. "

It is important to emphasize that the participation of our Institute in the “Science

without Borders” Program is also contributing to improving the quality of our research.

Researchers in INBEB have a strong association with researchers and international institutions.

We maintained a high degree of interaction with almost all of the foreign researchers initially

listed in the project when it was submitted. It is worth noting that we have incorporated

Professor Kurt Wüthrich, Nobel Prize in Chemistry, as a Special Visiting Researcher (CsF) of

the INBEB. He has an office and lab facilities where he is the formal advisor of a graduate

student and of a post-doc. They also worked with Professor Wüthrich at the Scripps Research

Institute for 12 months, as visiting scholars. We also host, as a CSsF Special Visiting

Researcher, Prof. Dmitry Korzhnev, (University of Connecticut Health Center), a great expert

on the studies of excited states of proteins by NMR. In addition, we had several undergraduate,

graduate and post-doc students visiting international institutions for periods from 6 to 12

months.

We believe that we have been able to consolidate a highly multidisciplinary program in

the biomedical and biotechnological area. More important than the more than XXX articles

published in peer-reviewed journals over the last four years is that they reflect a highly

collaborative research effort. Not counted in this publication are the many studies conducted by

researchers not belonging the INCT network, but who use the facilities of INBEB. Not less

important is the fact that the research conducted in INBEB resulted in XXX new Masters and

XXX new PhDs.

However, looking forward to the challenges imposed for the coming years, we intend to make

some changes, which will begin in 2017. We feel the need to promote a restructuring of Associated

Laboratories, with the merge of some groups and incorporation of other excellence teams, such

246


246

as the new NMR of Protein Structure and Dynamics by NMR, to be coordinated by researcher

Ana Paula Valente (IBqM / UFRJ), who Will be advised by the Nobel laureate Kurt Wuthrich

(Visiting Professor at INBEB / UFRJ). Another example is the new Associated Laboratory of

Neurodegenerative Diseases and Cancer, coordinated by the researcher Fernanda Tovar Moll

(ICB / UFRJ and IDor), which will incorporate more closely translational research in

partnership with IDOr. Therefore, the basic organizational structure of INBEB will be

maintained, but the restructure of some LAs aim to achieve some defined scientific goals:

1. Prioritize thematic areas always considering the agents and their respective diseases,

emphasizing a structural approach (from macromolecule to cells and tissues);

2. To advance in the field of experimental chemotherapy in vitro and in vivo, seeking to

reach clinical trials;

3. Development of new antiviral and antiparasitic drugs focusing on diseases that are

relevant to Brazilian public health;

4. Development of new diagnostic and therapeutic tools for neurodegenerative diseases

and cancer;

5. Association with the business community (research equipment, diagnostic kits,

bioimaging software, drugs, etc.); and

6. Supporting promising young teacher-researchers located in various regions of the

country to consolidate their research groups.

The operating structure of INBEB will be used as means of integration between the

groups. The objective of the 21 LAs is to act in an integrated way to solve important biological

problems described in the four major themes highlighted in Groups I through IV below:

• Group I: Proteins Amyloidogens and Prions: Neurodegenerative Diseases and Poor

Protein Folding;

• Group II: Viruses and Respective Diseases;

• Group III: Eukaryotic Microorganisms and Respective Diseases;

• Group IV: Tumor and Oncogenic Suppression Proteins in Cancer.

In this new proposal, the INBEB program incorporates a focus on clustering efforts,

joining all the installed capacity of INBEB built in the previous phase, now applied to new

thematic foci that permeate studies with pathophysiological agents and their corresponding

diseases. We define thematic priorities that can further increase cooperation among the various

groups, resulting in the development of projects with greater depth and scope, as well as a

multidisciplinary approach in order to achieve greater impact.

247


247

Spported by:

QUADRENNIAL REPORT - Instituto Nacional de Ciência e ...

Documents

Transcript of QUADRENNIAL REPORT - Instituto Nacional de Ciência e ...