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Glycomic regulation of human B cells
No full textAll leukocytes are coated with a dense layer of carbohydrates called the glycocalyx. Initially believed to serve largely biophysical roles, the glycocalyx is increasingly recognized as a gatekeeper of leukocyte interactions with the cellular microenvironment, in part by mediating specific contacts with carbohydrate-binding proteins (lectins). Far from inert bystanders, the carbohydrate moieties (glycans) decorating leukocyte glycoproteins are highly dynamic and undergo significant restructuring in different immunological contexts. On T cells, which confer cell-mediated immunity, activation and differentiation are known to induce global alterations in the T cell glycan repertoire (glycome) that regulate T cell survival and homing to inflamed tissues. Yet, for B cells, which confer humoral immunity, similar alterations to the glycome have not been extensively reported.
Here, we tested the hypothesis that glycomic changes associated with B cell differentiation are critical for normal B cell function. This hypothesis was tested in two related studies. In the first study, we profiled the repertoire of asparagine (N)-linked glycans expressed by B cells at multiple stages of differentiation, including naïve, germinal center (GC), and memory B cell stages. Results from this study revealed that while all B cells expressed N-glycans replete with lactosamine chains, these lactosamine moieties were modified with I-branches in GC B cells due to upregulation of the glycosyltransferase GCNT2. Functional studies revealed that I-branches served as a selective regulator of binding of a family of immunoregulatory lectins known as galectins. In the second study, the function of one of these galectins, galectin-9, was investigated in B cells. These studies revealed that galectin-9 was highly expressed by naïve B cells and bound the glycoprotein CD45. Mechanistically, galectin-9 promoted inhibitory signaling via the Lyn-CD22-SHP-1 pathway and ultimately attenuated B cell receptor-mediated calcium signaling and activation. Perturbation of B cell-intrinsic galectin-9 revealed that galectin-9 could serve as an autologous regulator of B cell receptor signaling. In all, our study highlights a novel glycomic mechanism regulating B cell activation, and opens new avenues of investigation into the roles of galectin-9 in B cell peripheral tolerance and autoimmune disease.Medical SciencesMedical SciencesB cell; B lymphocyte; glycan; carbohydrate; glycomics; galectin; GCNT2; I-branch; I-blood group antigen; CD22; CD4
Tolling for Autoimmunity—Prime Time for 7
No full textThe reason certain self-antigens are consistently targeted by autoantibodies may be because they are self-adjuvants. Two papers in this issue of Immunity provide important insights into the contribution of Toll-like receptors in systemic autoimmune disease (Berland et al., 2006; Christensen et al., 2006)
Toll-Like Receptors and Innate Immune Responses in Systemic Lupus Erythematosus
Full text linkA series of discoveries over the past several years has provided a new paradigm for understanding autoimmunity in systemic lupus erythematosus. The discoveries of pattern recognition receptors and of how these receptors can be recruited into autoimmune responses underpin this paradigm. The implications of these observations continue to unfold with ongoing investigation into the range and specificity of pattern recognition receptors, into how immune complexes containing nucleic acids trigger these receptors, into how endogenous macromolecular 'danger signals' stimulate innate immune responses, and into the effect of pattern recognition receptor activation on various cell types in initiating and perpetuating autoimmunity. The development of clinical trials using therapeutic agents that target components of the innate immune system suggests that these advances may soon culminate in new medications for treating patients with systemic lupus erythematosus
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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