1,720,987 research outputs found
Use of genome wide expression profiles in analysis of T cell dysfunction in Hepatitis C virus infection
Full text linkDuring the course of infection with chronic pathogens such as Hepatitis C virus (HCV), Hepatitis B virus (HBV) and HIV, virus-specific CD8+ T cells differentiate into heterogeneous dysfunctional subpopulations. Advances in multi-parameter flow cytometry have allowed these subpopulations to be further classified into classes of exhausted T cells, primarily by their expression of multiple inhibitory receptors. However, the exact phenotype of CD8+ T cells during exhaustion is an area of great interest as many inhibitory receptors are also expressed on functional CD8+ T cells. Discovering novel and specific markers of T cell exhaustion is fundamental in developing strategies to restore CD8+ T cell function in chronic viral infections. Recently, genome wide expression profiles have identified broad molecular phenotypes in exhausted T cells that could not have been discovered by flow cytometry alone. I show how similar genomic approaches identify and further characterise the ectonucleotidase CD39 as a novel marker of CD8+ T cell exhaustion in chronic viral infection. I show that CD39 is highly expressed in HCV and HIV-specific CD8+ T cells and that CD39+ CD8+ T cells are enriched with gene signatures of exhaustion. CD39 is highly co-expressed with multiple inhibitory receptors including PD-1, enzymatically active on CD8+ T cells in HCV infection and positively correlated with viral load in both HCV and HIV. I also demonstrate the discovery of a novel CD39High population of cells in the mouse model of chronic Lymphocytic Choriomenigitis Virus (LCMV) infection, which express the highest degrees of PD-1, LAG3 and 2B4 in the CD39+ fraction. Thus, CD39 is a novel and specific marker of severe CD8+ T cell exhaustion in human and animal models of chronic viral infection
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
Recommended from our members
Regulation of immune homeostasis, autoimmunity and protective immunity by the CD160 and PD-1 co-inhibitory molecules
No full textCo-stimulatory and co-inhibitory pathways are critical for immune homeostasis, immune tolerance and protective immunity. In this thesis, we analyzed how two co-inhibitory molecules, CD160 and programmed cell death-1 (PD-1), regulate immune homeostasis, autoimmunity and protective immunity.
The function of CD160 on T cells remains unclear with conflicting studies supporting both co-inhibitory and co-stimulatory roles. Here we demonstrate that CD160 has a co-stimulatory role in promoting CD8+ T cell effector functions needed for optimal clearance of oral Listeria monocytogenes (Lm) infection. CD160–/– mice did not clear oral Lm as efficiently as WT littermates. Defective bacterial clearance is due to compromised IEL and splenic CD8+ T cell functions – reduced granzyme B, TNF-α and IFN-γ production in CD160–/– IELs and splenic CD8+ T cells. Adoptive transfer studies showed that RAG–/– recipients receiving CD160–/– CD8+ T cells had a higher mortality and a higher bacteria burden compared to RAG–/– recipients receiving WT CD8+ T cells. These findings demonstrate that CD160 provides key co-stimulatory signals to CD8+ T cells for protective immunity during an acute mucosal bacteria infection.
Secondly, we studied the role of PD-1 on regulatory T cells (Tregs). The PD-1 co-inhibitory pathway is critical for immune tolerance. Studies of PD-1 function have focused primarily on effector T cells, and little is known about how PD-1 regulates Tregs, which are critical for maintaining the balance between tolerance and immunity. We demonstrated that PD-1 deficient Tregs have increased suppressive capacity in vitro and in vivo compared to WT Tregs. Mice lacking PD-1 selectively on Tregs had delayed onset and severity of experimental autoimmune encephalitis (EAE) and were protected against diabetes in non-obese diabetic (NOD) mice. The enhanced suppressive capacity in PD-1 deficient Tregs is due to down-regulation of the PI3K-AKT pathway in Tregs and PD-1 deficient Tregs have altered bioenergetics. Our findings demonstrate that signals through PD-1 in Treg cells restrain their activation and function and are vital for optimal homeostasis, protective immunity and tolerance.
These findings advance our mechanistic understanding of how co-inhibitory molecules on different immune cell types regulate immune homeostasis, autoimmunity and immunity.Biology, Molecular and Cellula
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
