Revisiting the Tissue Microenvironment of Infectious Mononucleosis: Identification of EBV Infection in T Cells and Deep Characterization of Immune Profiles

To aid understanding of primary EBV infection, we have performed an in depth analysis of EBV-infected cells and of local immune cells in tonsils from infectious mononucleosis (IM) patients. We show that EBV is present in approximately 50% of B-cells showing heterogeneous patterns of latent viral gene expression probably reflecting different stages of infection. While the vast majority of EBV+ cells are B-cells, around 9% express T-cell antigens, with a predominance of CD8+ over CD4+ cells. PD-L1 was expressed by a median of 14% of EBV+ cells. The numbers of EBER+PD-L1+ cells were directly correlated with the numbers of EBER+CD3+ and EBER+CD8+ cells suggesting a possible role for PD-L1 in EBV infection of T-cells. The microenvironment of IM tonsils was characterized by a predominance of M1-polarized macrophages over M2-polarized cells. However, at the T-cell level, a heterogeneous picture emerged with numerous Th1/cytotoxic cells accompanied and sometimes outnumbered by Th2/regulatory T-cells. Further, we observed a direct correlation between the numbers of Th2-like cells and EBV– B-cells. Also, a prevalence of cytotoxic T-cells over Th2-like cells was associated with an increased viral load. These observations point to contribution of B- and Th2-like cells to the control of primary EBV infection. 35% of CD8+ cells were differentiated CD8+TBET+ cells, frequently detected in post-capillary venules. An inverse correlation was observed between the numbers of CD8+TBET+ cells and viral load suggesting a pivotal role for these cells in the control of primary EBV infection. Our results provide the basis for a better understanding of immune reactions in EBV-associated tumors

Técnicas de Extração de Informação para Avaliação da Qualidade de Páginas Web com o Uso de Ontologias

A qualidade dos conteúdos das páginas Web podem ser determinadas parcialmente através de indicadores como autoria do página, presença de referencias e de propriedade. Este artigo discute a aplicação de técnicas de extração de informação sobre a identificação de indicadores de qualidade, especificamente autoria. Ao contrário de outras técnicas de extração, as técnicas desenvolvidas neste trabalho não utilizam a estrutura da página como principal elemento de análise, voltando sua atenção para o conteúdo extraido. O objetivo final do trabalho é criar uma ferramenta que possibilita a avaliação da qualidade de sites de saúde. Com as entidades extraídas é populado uma ontologia onde estão definidos os critérios de qualidade para as páginas Web

Redox regulation of the proteasome via S-glutathionylation

The proteasome is a multimeric and multicatalytic intracellular protease responsible for the degradation of proteins involved in cell cycle control, various signaling processes, antigen presentation, and control of protein synthesis. The central catalytic complex of the proteasome is called the 20S core particle. The majority of these are flanked on one or both sides by regulatory units. Most common among these units is the 19S regulatory unit. When coupled to the 19S unit, the complex is termed the asymmetric or symmetric 26S proteasome depending on whether one or both sides are coupled to the 19S unit, respectively. The 26S proteasome recognizes poly-ubiquitinylated substrates targeted for proteolysis. Targeted proteins interact with the 19S unit where they are deubiquitinylated, unfolded, and translocated to the 20S catalytic chamber for degradation. The 26S proteasome is responsible for the degradation of major proteins involved in the regulation of the cellular cycle, antigen presentation and control of protein synthesis. Alternatively, the proteasome is also active when dissociated from regulatory units. This free pool of 20S proteasome is described in yeast to mammalian cells. The free 20S proteasome degrades proteins by a process independent of poly-ubiquitinylation and ATP consumption. Oxidatively modified proteins and other substrates are degraded in this manner. The 20S proteasome comprises two central heptamers (β-rings) where the catalytic sites are located and two external heptamers (α-rings) that are responsible for proteasomal gating. Because the 20S proteasome lacks regulatory units, it is unclear what mechanisms regulate the gating of α-rings between open and closed forms. In the present review, we discuss 20S proteasomal gating modulation through a redox mechanism, namely, S-glutathionylation of cysteine residues located in the α-rings, and the consequence of this post-translational modification on 20S proteasomal function.FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo)Instituto Nacional de Ciência, Tecnologia e Inovação de Processos Redox em BioMedicinaConselho Nacional de Ciência e Tecnologia (CNPq)CAPE

How students perceive medical competences: a cross-cultural study between the Medical Course in Portugal and African Portuguese Speaking Countries

<p>Abstract</p> <p>Background</p> <p>A global effort has been made in the last years to establish a set of core competences that define the essential professional competence of a physician. Regardless of the environment, culture or medical education conditions, a set of core competences is required for medical practice worldwide. Evaluation of educational program is always needed to assure the best training for medical students and ultimately best care for patients. The aim of this study was to determine in what extent medical students in Portugal and Portuguese speaking African countries, felt they have acquired the core competences to start their clinical practice. For this reason, it was created a measurement tool to evaluate self-perceived competences, in different domains, across Portuguese and Portuguese-speaking African medical schools.</p> <p>Methods</p> <p>The information was collected through a questionnaire that defines the knowledge, attitudes and skills that future doctors should acquire. The Cronbach's Alpha and Principal Components Analysis (PCA) were used to evaluate the reliability of the questionnaire. In order to remove possible confounding effect, individual scores were standardized by country.</p> <p>Results</p> <p>The order of the domain's scores was similar between countries. After standardization, Personal Attitudes and Professional Behavior showed median scores above the country global median and Knowledge alone showed median score below the country global median. In Portugal, Clinical Skills showed score below the global median. In Angola, Clinical Skills and General Skills showed a similar result. There were only significant differences between countries in Personal Attitudes (p < 0.001) and Professional Behavior (p = 0.043).</p> <p>Conclusions</p> <p>The reliability of the instrument in Portuguese and Portuguese-speaking African medical schools was confirmed. Students have perceived their level of competence in personal attitudes in a high level and in opposite, knowledge and clinical skills with some weaknesses.</p