Quantitative Proteomic Analysis Reveals Changes in the Benchmark Corynebacterium pseudotuberculosis Biovar Equi Exoproteome after Passage in a Murine Host

Corynebacterium pseudotuberculosis biovar equi is the etiologic agent of ulcerative lymphangitis. To investigate proteins that could be related to the virulence of this pathogen, we combined an experimental passage process using a murine model and high-throughput proteomics with a mass spectrometry, data-independent acquisition (LC-MSE) approach to identify and quantify the proteins released into the supernatants of strain 258_equi. To our knowledge, this approach allowed characterization of the exoproteome of a C. pseudotuberculosis equi strain for the first time. Interestingly, the recovery of this strain from infected mouse spleens induced a change in its virulence potential, and it became more virulent in a second infection challenge. Proteomic screening performed from culture supernatant of the control and recovered conditions revealed 104 proteins that were differentially expressed between the two conditions. In this context, proteomic analysis of the recovered condition detected the induction of proteins involved in bacterial pathogenesis, mainly related to iron uptake. In addition, KEGG enrichment analysis showed that ABC transporters, bacterial secretion systems and protein export pathways were significantly altered in the recovered condition. These findings show that secretion and secreted proteins are key elements in the virulence and adaptation of C. pseudotuberculosis. Collectively, bacterial pathogenesis-related proteins were identified that contribute to the processes of adherence, intracellular growth and evasion of the immune system. Moreover, this study enhances our understanding of the factors that may influence the pathogenesis of C. pseudotuberculosis.Fil: Marques Da Silva, Wanderson. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasil. Institut National de la Recherche Agronomique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carvalho, Rodrigo D. De Oliveira. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Dorella, Fernanda A.. Universidade Federal de Minas Gerais; BrasilFil: Folador, Edson L.. Universidade Federal da Paraíba. Centro de Biotecnologia; BrasilFil: Souza, Gustavo H. M. F.. Waters Corporation; BrasilFil: Pimenta, Adriano M. C.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Figueiredo, Henrique C. P.. Universidade Federal de Minas Gerais; BrasilFil: Le Loir, Yves. Institut National de la Recherche Agronomique; FranciaFil: Silva, Artur. Universidade Federal do Pará; BrasilFil: Azevedo, Vasco. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasi

Phase II clinical study of an association for the treatment of interstitial cystitis (Cystex?).

Painful bladder syndrome associated with interstitial cystitis (PBS/IC) is a clinical condition characterized pelvic pain, urinary urgency, and urinary frequency. In this study, 22 patients were assigned to make two visits over a three weeks period. The patients were randomly, double-blinded assigned in two groups. The first group received Cystex? capsules. The second group received placebo capsules. Two capsules were taken three times a day away from meals. The change from baseline in the O?Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and intensity of pain and urgency have been chosen as secondary outcome parameters. Mood as well as physical and sexual activity were rated by 10 questions on a scale 0 to 6. The ratings were analyzed and the average for each patient in both groups Cystex? and placebo was determined as the quality of life index. For the primary outcome there was a statistically significant difference between the groups. Mean symptom score-sum decreased from 28.4 to 20.5 in the Cystex? group compared with 29.5 to 26.8 in the placebo group (p<0.05). For the secondary end points, pain and urgency intensity improved statistically significantly in the Cystex? group compared with the placebo group (p<0.05). The frequency and functional bladder capacity improved to greater degree in the Cystex? group. The differences were statistically significant for comparison of frequency (p<0.05) and not for functional bladder capacity (p>0.05). In our study, Cystex? enhanced quality of life over the placebo showing a statistically significant. This trial have shown that the efficacy and safety of therapy with Cystex? in the treatment of interstitial cystitis and is an alternative for patients suffering from this pathology. Therefore, it can be concluded that the composition of Cystex?, increased the quality of life in treated patients

Os museus históricos e pedagógicos do estado de São Paulo

This paper analyzes the creation of the Historical and Pedagogical Museums network in the State of São Paulo between 1956 and 1973, mainly taking into consideration the concept for creation, the program, and the role of the museum in society. This work covers a period until the end of the 1990's, when the curators of the museums, which belonged to the State until that time, was transferred to the municipalities by means of a "municipalization" process coordinated by the Department of Museums and Archives of the State Department of Cultural Affairs (DEMA-SEC). It also shows that the implementation of this museums network - among other initiatives in the fields of education and of culture - addressed earlier needs of asserting an identity, emphasizing through projects of this type the hegemonic character of the State. This allowed to align the initiative of creating the museums with others actions carried out by the State before, and also enabled that this topic was take out from its long isolation from the study of State history. It also considers the web of relationships existing among the various sectors with which museums were connected, such as education, culture, and the São Paulo Historical and Geographical Institute, the Government, and Society. The implementation of Historical and Pedagogical Museums by means of State action, through its Departments of Education (from 1956 to 1968) and Cultural Affairs (from 1968 to 1998) was one of the ways through which the Government orientated its activities during those years in the fields of history, education and culture. The central thesis is that the implementation of these museums has fully addressed the aspirations of society at the time, while, at the same time, underscoring the logic behind the ideation that has oriented the characteristic mode of operation of museums during the years in which their curatorship was exercised by the Government, and proposes to consider them as a paradigm for "historical museums of the State of São Paulo".Este estudo analisa a criação da rede de museus históricos e pedagógicos do estado de São Paulo entre os anos de 1956 e 1973, sobretudo quanto ao conceito de criação, de programa e de função de museu na sociedade. Tal análise estende-se ao final da década de 1990, quando a tutela dos museus, até então estadual, é transferida às cidades por meio do processo de municipalização, coordenado pelo Departamento de Museus e Arquivos, da Secretaria de Estado da Cultura (Dema-SEC). Em meio a outras iniciativas nos campos da educação e da cultura, aborda a correspondência existente entre a implantação da rede desses museus e antigas necessidades de afirmação identitária, ao evidenciar, por meio de projetos desta natureza, o caráter hegemônico do Estado e sua atuação em campos como o da história, o da educação e o da cultura. Isso permitiu alinhar a iniciativa de criação dos museus a outras anteriormente promovidas pelo estado de São Paulo e possibilitar que o tema escapasse de um prolongado isolamento no estudo da história paulista. Trata, também, da trama de relações existentes entre diversos setores ligados aos museus - educação, cultura, Instituto Histórico e Geográfico de São Paulo (IHGSP), poder público e sociedade. A hipótese central é de que a implantação desses museus correspondeu plenamente às aspirações da sociedade de uma época, ao mesmo tempo em que evidencia a lógica da ideação que determinou o modo característico de atuação dos museus nos anos em que estiveram sob a tutela do governo estadual, propondo, assim, entendê-los como paradigma de "museu histórico do estado de São Paulo"

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

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+ 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. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

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+ 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. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p