1,721,025 research outputs found
Immunological insights in the treatment of chronic hepatitis B
Hepatitis B virus (HBV) causes either acute or chronic liver diseases. Chronic hepatitis B (CHB) often progresses to the development of cirrhosis and hepatocellular carcinoma. As HBV is extremely noncytopathic, immunological events play a key role in the infection outcome. Indeed, adaptive immune responses trigger viral clearance during acute infection and viral persistence reflects the failure to generate and maintain such responses. Current therapies for patients with CHB rely on direct-acting antivirals (DAAs) that suppress viral replication without eradicating HBV from the liver. Cure of CHB may well require combining these and forthcoming DAAs with immune-stimulating approaches of different nature and function. Here, we review the relative potential of these combination therapies
The role of type I interferons in CD4 + T cell differentiation
Type I interferons (IFNs) released upon viral infections play different and opposing roles in disease outcome. This pleiotropic effect is mainly influenced by the cellular sources, timing and target cells for these molecules. The effect of type I IFN signaling on the activation and differentiation of antiviral CD4 + T cells remains ill defined, with studies reporting either a beneficial or a detrimental role, depending on the context of infection. This review will highlight several recent studies that have investigated the role of type I IFNs in the priming and polarization of CD4 + T cells and discuss areas of uncertainty that require further investigation
Intestinal Flossing Keeps Pathogens at Bay
Intraepithelial lymphocytes (IELs) are tissue-resident immune cells that surveil the intestine and provide the first line of defense against pathogens. Reporting in Cell, van Konijnenburg et al. (2017) combine high-resolution microscopy and intersectional genetic tools to provide a detailed characterization of IEL dynamics in response to both commensal and pathogenic microorganisms. Intraepithelial lymphocytes (IELs) are tissue-resident immune cells that surveil the intestine and provide the first line of defense against pathogens. Reporting in Cell, van Konijnenburg et al. (2017) combine high-resolution microscopy and intersectional genetic tools to provide a detailed characterization of IEL dynamics in response to both commensal and pathogenic microorganisms
Viral subversion of B cell responses within secondary lymphoid organs
Antibodies play a crucial role in virus control. The production of antibodies requires virus-specific B cells to encounter viral antigens in lymph nodes, become activated, interact with different immune cells, proliferate and enter specific differentiation programmes. Each step occurs in distinct lymph node niches, requiring a coordinated migration of B cells between different subcompartments. The development of multiphoton intravital microscopy has enabled researchers to begin to elucidate the precise cellular and molecular events by which lymph nodes coordinate humoral responses. This Review discusses recent studies that clarify how viruses interfere with antibody responses, highlighting how these mechanisms relate to our topological and temporal understanding of B cell activation within secondary lymphoid organs
Arenaviral infection causes bleeding in mice due to reduced serotonin release from platelets
Bleeding correlates with disease severity in viral hemorrhagic fevers. We found that the increase in type I interferon (IFN-I) in mice caused by infection with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV; an arenavirus) reduced the megakaryocytic expression of genes encoding enzymes involved in lipid biosynthesis (cyclooxygenase 1 and thromboxane A synthase 1) and a thrombopoietic transcription factor (Nf-e2). The decreased expression of these genes was associated with reduced numbers of circulating platelets and defects in the arachidonic acid synthetic pathway, thereby suppressing serotonin release from 6-granules in platelets. Bleeding resulted when severe thrombocytopenia and altered platelet function reduced the amount of platelet-derived serotonin below a critical threshold. Bleeding was facilitated by the absence of the activity of the kinase Lyn or the administration of aspirin, an inhibitor of arachidonic acid synthesis. Mouse platelets were not directly affected by IFN-I because they lack the receptor for the cytokine (IFNAR1), suggesting that transfusion of normal platelets into LCMV-infected mice could increase the amount of platelet-released serotonin and help to control hemorrhage
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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