1,720,967 research outputs found
Positive and negative regulation of antigen receptor signaling by the Shc family of protein adapters
No full textThe Shc adapter family includes four members that are expressed as multiple isoforms and participate in signaling by a variety of cell-surface receptors. The biological relevance of Shc proteins as well as their variegated function, which relies on their highly conserved modular structure, is underscored by the distinct and dramatic phenotypic alterations resulting from deletion of individual Shc isoforms both in the mouse and in two model organisms, Drosophila melanogaster and Caenorhabditis elegans. The p52 isoform of ShcA couples antigen and cytokine receptors to Ras activation in both lymphoid and myeloid cells. However, the recognition of the spectrum of activities of p52ShcA in the immune system has been steadily expanding in recent years to other fundamental processes both at the cell and organism levels. Two other Shc family members, p66ShcA and p52ShcC/Rai, have been identified recently in T and B lymphocytes, where they antagonize survival and attenuate antigen receptor signaling. These developments reveal an unexpected and complex interplay of multiple Shc proteins in lymphocytes
The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 cell development.
No full textObjective
Rai acts as a negative regulator of antigen receptor signaling in T and B cells. Rai-/- mice develop lupus-like autoimmunity associated to the spontaneous activation of self-reactive lymphocytes. Here we have addressed the potential role of Rai in the development of the proinflammatory Th1 and Th17 subsets.
Materials and methods
Lymph node T cells or naïve T cells were isolated from wild-type and Rai-/- mice and their cytokine profile was determined by ELISPOT and qRT-PCR both as such and after stimulation in vitro with immobilized anti-CD3 mAb in the presence or absence of polarizing cytokines. The expression of rai was measured in PBL from SLE patients and healthy donors by qRT-PCR.
Results
We show that Rai-/- mice display a spontaneous Th1/Th17 bias. In vitro polarization experiments demonstrate that rai deficiency favours the development and expansion of Th17, but not Th1, cells, indicating that Rai modulates TCR signaling to antagonize the pathways driving naive CD4+ T cell differentiation to the Th17 lineage. Th1 and Th17 cell infiltrates were found in the kidneys of Rai-/- mice, providing evidence that Rai deficiency contributes to the development of lupus nephritis not only by enhancing lymphocyte activation but also by promoting the development and expansion of proinflammatory effector T cells. Interestingly, T cells from SLE patients were found to have a defect in Rai expression, suggesting a role for Rai in disease pathogenesis.
Conclusions
We have identified Rai as a negative regulator of Th17 cell differentiation and expansion in the mouse and found evidence of an impairment of Rai expression in PBL from SLE patients
The adenylate cyclase toxin of Bacillus anthracis is a potent promoter of Th17 cell development
No full text
The Rai adaptor protein in Th17 cell differentiation, effector function and chemotaxis and in the pathogenesis of multiple sclerosis
No full textBackground
We have previously reported that Rai deficiency in the mouse results in the development of lupus-like autoimmunity and showed that this could be accounted for, at least in part, by the function of Rai as an attenuator of antigen receptor signaling, such that Rai deficient T and B lymphocytes displayed spontaneous activation and proliferation and enhanced responses to antigen both in vitro and in vivo compared to wild-type controls (Savino et al. 2009). Based on the central implication of Th1 and Th17 cells in the pathogenesis of a wide range of autoimmune disorders, including lupus, multiple sclerosis and rheumatoid arthritis, we asked whether Rai could regulate not only the activation of T cells, but also their development to these proinflammatory effectors.
Aim of the project
The principal objectives of this project are: i) to assess the role of Rai on the differentiation, activation and chemotaxis of CD4+ T cell subsets; ii) to translate the results to the pathogenesis of multiple sclerosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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