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  1. Article: Standardization of a Continuous Assay for Glycosidases and Its Use for Screening Insect Gut Samples at Individual and Populational Levels.

    Profeta, Gerson S / Pereira, Jessica A S / Costa, Samara G / Azambuja, Patricia / Garcia, Eloi S / Moraes, Caroline da Silva / Genta, Fernando A

    Frontiers in physiology

    2017  Volume 8, Page(s) 308

    Abstract: Glycoside Hydrolases (GHs) are enzymes able to recognize and cleave glycosidic bonds. Insect GHs play decisive roles in digestion, in plant-herbivore, and host-pathogen interactions. GH activity is normally measured by the detection of a release from the ...

    Abstract Glycoside Hydrolases (GHs) are enzymes able to recognize and cleave glycosidic bonds. Insect GHs play decisive roles in digestion, in plant-herbivore, and host-pathogen interactions. GH activity is normally measured by the detection of a release from the substrate of products as sugars units, colored, or fluorescent groups. In most cases, the conditions for product release and detection differ, resulting in discontinuous assays. The current protocols result in using large amounts of reaction mixtures for the obtainment of time points in each experimental replica. These procedures restrain the analysis of biological materials with limited amounts of protein and, in the case of studies regarding small insects, implies in the pooling of samples from several individuals. In this respect, most studies do not assess the variability of GH activities across the population of individuals from the same species. The aim of this work is to approach this technical problem and have a deeper understanding of the variation of GH activities in insect populations, using as models the disease vectors
    Language English
    Publishing date 2017-05-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2017.00308
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Binding and structural analyses of potent inhibitors of the human Ca

    Profeta, Gerson S / Dos Reis, Caio V / Santiago, André da S / Godoi, Paulo H C / Fala, Angela M / Wells, Carrow I / Sartori, Roger / Salmazo, Anita P T / Ramos, Priscila Z / Massirer, Katlin B / Elkins, Jonathan M / Drewry, David H / Gileadi, Opher / Couñago, Rafael M

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 16452

    Abstract: Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CAMKK2) acts as a signaling hub, receiving signals from various regulatory pathways and decoding them via phosphorylation of downstream protein kinases - such as AMPK (AMP-activated protein kinase) ... ...

    Abstract Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CAMKK2) acts as a signaling hub, receiving signals from various regulatory pathways and decoding them via phosphorylation of downstream protein kinases - such as AMPK (AMP-activated protein kinase) and CAMK types I and IV. CAMKK2 relevance is highlighted by its constitutive activity being implicated in several human pathologies. However, at present, there are no selective small-molecule inhibitors available for this protein kinase. Moreover, CAMKK2 and its closest human homolog, CAMKK1, are thought to have overlapping biological roles. Here we present six new co-structures of potent ligands bound to CAMKK2 identified from a library of commercially-available kinase inhibitors. Enzyme assays confirmed that most of these compounds are equipotent inhibitors of both human CAMKKs and isothermal titration calorimetry (ITC) revealed that binding to some of these molecules to CAMKK2 is enthalpy driven. We expect our results to advance current efforts to discover small molecule kinase inhibitors selective to each human CAMKK.
    MeSH term(s) Animals ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/antagonists & inhibitors ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/chemistry ; Drug Discovery ; Humans ; Ligands ; Molecular Conformation ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Binding ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Recombinant Proteins ; Structure-Activity Relationship
    Chemical Substances Ligands ; Protein Kinase Inhibitors ; Recombinant Proteins ; CAMKK2 protein, human (EC 2.7.11.17) ; Calcium-Calmodulin-Dependent Protein Kinase Kinase (EC 2.7.11.17)
    Language English
    Publishing date 2019-11-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-52795-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner.

    Saccon, Tatiana Dandolini / Mousovich-Neto, Felippe / Ludwig, Raissa Guimarães / Carregari, Victor Corasolla / Dos Anjos Souza, Ana Beatriz / Dos Passos, Amanda Stephane Cruz / Martini, Matheus Cavalheiro / Barbosa, Priscilla Paschoal / de Souza, Gabriela Fabiano / Muraro, Stéfanie Primon / Forato, Julia / Amorim, Mariene Ribeiro / Marques, Rafael Elias / Veras, Flavio Protasio / Barreto, Ester / Gonçalves, Tiago Tomazini / Paiva, Isadora Marques / Fazolini, Narayana P B / Onodera, Carolina Mie Kawagosi /
    Martins Junior, Ronaldo Bragança / de Araújo, Paulo Henrique Cavalcanti / Batah, Sabrina Setembre / Viana, Rosa Maria Mendes / de Melo, Danilo Machado / Fabro, Alexandre Todorovic / Arruda, Eurico / Queiroz Cunha, Fernando / Cunha, Thiago Mattar / Pretti, Marco Antônio M / Smith, Bradley Joseph / Marques-Souza, Henrique / Knittel, Thiago L / Ruiz, Gabriel Palermo / Profeta, Gerson S / Fontes-Cal, Tereza Cristina Minto / Boroni, Mariana / Vinolo, Marco Aurélio Ramirez / Farias, Alessandro S / Moraes-Vieira, Pedro Manoel M / Bizzacchi, Joyce Maria Annichino / Teesalu, Tambet / Chaim, Felipe David Mendonça / Cazzo, Everton / Chaim, Elinton Adami / Proença-Módena, José Luiz / Martins-de-Souza, Daniel / Osako, Mariana Kiomy / Leiria, Luiz Osório / Mori, Marcelo A

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 5722

    Abstract: Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat ... ...

    Abstract Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion.
    MeSH term(s) Adipose Tissue ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Cytokines ; Humans ; SARS-CoV-2
    Chemical Substances Cytokines ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2022-09-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-33218-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

    Brunetti, Natalia S / Davanzo, Gustavo G / de Moraes, Diogo / Ferrari, Allan J R / Souza, Gabriela F / Muraro, Stéfanie Primon / Knittel, Thiago L / Boldrini, Vinicius O / Monteiro, Lauar B / Virgílio-da-Silva, João Victor / Profeta, Gerson S / Wassano, Natália S / Nunes Santos, Luana / Carregari, Victor C / Dias, Artur H S / Veras, Flavio P / Tavares, Lucas A / Forato, Julia / Castro, Icaro M S /
    Silva-Costa, Lícia C / Palma, André C / Mansour, Eli / Ulaf, Raisa G / Bernardes, Ana F / Nunes, Thyago A / Ribeiro, Luciana C / Agrela, Marcus V / Moretti, Maria Luiza / Buscaratti, Lucas I / Crunfli, Fernanda / Ludwig, Raissa G / Gerhardt, Jaqueline A / Munhoz-Alves, Natália / Marques, Ana Maria / Sesti-Costa, Renata / Amorim, Mariene R / Toledo-Teixeira, Daniel A / Parise, Pierina Lorencini / Martini, Matheus Cavalheiro / Bispos-Dos-Santos, Karina / Simeoni, Camila L / Granja, Fabiana / Silvestrini, Virgínia C / de Oliveira, Eduardo B / Faca, Vitor M / Carvalho, Murilo / Castelucci, Bianca G / Pereira, Alexandre B / Coimbra, Laís D / Dias, Marieli M G / Rodrigues, Patricia B / Gomes, Arilson Bernardo S P / Pereira, Fabricio B / Santos, Leonilda M B / Bloyet, Louis-Marie / Stumpf, Spencer / Pontelli, Marjorie C / Whelan, Sean / Sposito, Andrei C / Carvalho, Robson F / Vieira, André S / Vinolo, Marco A R / Damasio, André / Velloso, Licio / Figueira, Ana Carolina M / da Silva, Luis L P / Cunha, Thiago Mattar / Nakaya, Helder I / Marques-Souza, Henrique / Marques, Rafael E / Martins-de-Souza, Daniel / Skaf, Munir S / Proenca-Modena, Jose Luiz / Moraes-Vieira, Pedro M M / Mori, Marcelo A / Farias, Alessandro S

    eLife

    2023  Volume 12

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; CD8-Positive T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Lung
    Language English
    Publishing date 2023-07-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.84790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes

    Davanzo, Gustavo G. / Codo, Ana C. / Brunetti, Natalia S. / Boldrini, Vinciusi O. / Knittel, Thiago L. / Monterio, Lauar B. / de Moraes, Diogo / Ferrari, Allan J. R. / de Souza, Gabriela F. / Muraro, Stefanie P. / Profeta, Gerson . S / Wassano, Natalia S. / Santos, Luana N. / Carregari, Victor . C / Dias, Arthur . H. S / Virgilio-da-Silva, Joao Victor / Castro, Icaro / Silva-Costa, Licia . C / Palma, Andre /
    Mansour, Eli / Ulaf, Raisa G. / Bernardes, Ana F. / Nunes, Thyago A. / Ribeiro, Luciana C. / Agrela, Marcus V. / Moretti, Maria Luiza / Buscaratti, Lucas I. / Crunfli, Fernanda / Ludwig, Raissa . G / Gerhardt, Jaqueline A. / Seste-Costa, Renata / Forato, Julia / Amorin, Mariene . R / Texeira, Daniel A. T. / Parise, Pierina L. / Martini, Matheus C. / Bispo-dos-Santos, Karina / Simeoni, Camila L. / Granja, Fabiana / Silvestrini, Virginia C. / de Oliveira, Eduardo B. / Faca, Vitor M. / Carvalho, Murilo / Castelucci, Bianca G. / Pereira, Alexandre B. / Coimbra, Lais D. / Rodrigues, Patricia B. / Gomes, Arilson Bernardo S. P. / Pereira, Fabricio B. / Santos, Leonilda M. B. / Sposito, Andrei C. / Carvalho, Robson F. / Vieira, Andre S. / Vinolo, Marco A. R. / Damasio, Andre / Velloso, Licio A. / Nakaya, Helder I. / Marques-Souza, Henrique / Marques, Rafael E. / Martins-de-Souza, Daniel / Skaf, Munir S. / Proenca-Modena, Jose Luiz / Moraes-Vieira, Pedro M. / Mori, Marcelo A. / Farias, Alessandro S.

    medRxiv

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 (COVID-19). SARS-CoV-2 infects the lungs and may cause several immune-related ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 (COVID-19). SARS-CoV-2 infects the lungs and may cause several immune-related complications such as lymphocytopenia and cytokine storm which are associated with the severity of the disease and predict mortality . The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is not fully understood. Here we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2. Once inside T helper cells, SARS-CoV-2 assembles viral factories, impairs cell function and may cause cell death. SARS-CoV-2 infected T helper cells express higher amounts of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID- 19 patients.
    Keywords covid19
    Language English
    Publishing date 2020-09-28
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.09.25.20200329
    Database COVID19

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