1,721,107 research outputs found
The chromatin accessibility signature of aging in human blood leukocytes stem from CD8+ T cells.
Full text linkHuman aging is linked to changes in immune function that contribute to decreased responses to pathogens and increased systemic inflammation. Human aging is also associated with profound epigenetic changes across cell types and tissues. How these changes affect the aging –associated decline of the immune system is unknown. The Assay for Transposase Accessible Chromatin with sequencing technology (ATAC-seq) allowed us to study, at a system biology level, the open chromatin landscapes of human peripheral blood mononuclear cells (PBMCs), monocytes, purified B and T cell subsets from healthy young and healthy elderly individuals. We captured aging-associated epigenomic remodeling in PBMCs consisting of (1) systematic chromatin closing at promoters and enhancers targeting the T cell signaling and development and (2) chromatin opening, mostly at quiescent and repressed sites associated with cytotoxicity. Transcriptome profiling of the same individuals revealed gene expression changes concordant with epigenomic changes. Analysis of naïve and memory CD4+ and CD8+ T cell subsets demonstrated that the epigenomic signature of aging in PBMCs arises mostly from memory CD8+ T cells, indicating that aging differentially affects T cell epigenomes in a subset-specific manner. This study provides the first systems-level description of chromatin accessibility changes associated with immune aging in human PBMCs and T cell subsets. It revealed in PBMCs significant chromatin closing at promoters and enhancers, including at the IL7R locus and the IL-7 signaling pathway. Our study revealed individual-level variability in aging-associated chromatin remodeling and provided a systematic and modular tool for assessing deviations from chronological age. The open chromatin profiling of sorted T cell subsets, concluded that the chromatin "aging signature" captured in PBMCs, mostly stems from memory CD8+ T cells. The combined ATAC-seq/RNA-seq analyses uncovered epigenetic changes poised for expression changes and active noncoding elements (e.g., enhancers), both of which will be essential for understanding the regulatory mechanisms underlying immunosenescence. Nevertheless, ATAC-seq based open chromatin profiling is a straightforward approach to identify functional genomic regulatory regions, master regulators, and gene regulatory networks controlling complex in vivo processes. In our lab, ATAC-seq is utilized to understand the epigenetics differences in different immune cells and diseases
The chromatin accessibility signature of aging in human blood leukocytes stem from CD8+ T cells.
No full textHuman aging is linked to changes in immune function that contribute to decreased responses to pathogens and increased systemic inflammation. Human aging is also associated with profound epigenetic changes across cell types and tissues. How these changes affect the aging –associated decline of the immune system is unknown. The Assay for Transposase Accessible Chromatin with sequencing technology (ATAC-seq) allowed us to study, at a system biology level, the open chromatin landscapes of human peripheral blood mononuclear cells (PBMCs), monocytes, purified B and T cell subsets from healthy young and healthy elderly individuals. We captured aging-associated epigenomic remodeling in PBMCs consisting of (1) systematic chromatin closing at promoters and enhancers targeting the T cell signaling and development and (2) chromatin opening, mostly at quiescent and repressed sites associated with cytotoxicity. Transcriptome profiling of the same individuals revealed gene expression changes concordant with epigenomic changes. Analysis of naïve and memory CD4+ and CD8+ T cell subsets demonstrated that the epigenomic signature of aging in PBMCs arises mostly from memory CD8+ T cells, indicating that aging differentially affects T cell epigenomes in a subset-specific manner. This study provides the first systems-level description of chromatin accessibility changes associated with immune aging in human PBMCs and T cell subsets. It revealed in PBMCs significant chromatin closing at promoters and enhancers, including at the IL7R locus and the IL-7 signaling pathway. Our study revealed individual-level variability in aging-associated chromatin remodeling and provided a systematic and modular tool for assessing deviations from chronological age. The open chromatin profiling of sorted T cell subsets, concluded that the chromatin “aging signature” captured in PBMCs, mostly stems from memory CD8+ T cells. The combined ATAC-seq/RNA-seq analyses uncovered epigenetic changes poised for expression changes and active noncoding elements (e.g., enhancers), both of which will be essential for understanding the regulatory mechanisms underlying immunosenescence. Nevertheless, ATAC-seq based open chromatin profiling is a straightforward approach to identify functional genomic regulatory regions, master regulators, and gene regulatory networks controlling complex in vivo processes. In our lab, ATAC-seq is utilized to understand the epigenetics differences in different immune cells and diseases
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
Gene expression profiling to understand the alterations in the monocyte compartment of pediatric systemic lupus erythematosus.
No full textBlood monocytes from SLE patients display DC function, as they are able to induce the proliferation of allogeneic T cells. Furthermore, sera from SLE patients induce healthy monocytes to differentiate into DCs. This DC-inducing property is in part due to the presence of type-I IFNs in SLE sera, as well as other, yet uncharacterized factors. To understand these alterations, we performed a thorough phenotypic analysis and gene expression profiling of monocytes from children with active, newly diagnosed and untreated disease. Phenotypic analysis of freshly isolated SLE blood monocytes revealed a modest expansion of CD14highCD16+ cells and an otherwise lack of expression of molecules related to DC function. Further characterization of a fraction of SLE monocytes inducing allogeneic T cell proliferation revealed that upon contact with T cells, SLE monocytes secrete proinflammatory cytokines such as IL-1 and IL-6 and do upregulate expression of innate immunity receptors involved in DC differentiation and molecules responsible for antigen presentation. To recapitulate the initial events leading to monocyte differentiation in this disease, we studied the effects of SLE serum on healthy monocyte at the trasncriptional and protein levels. These studies revealed the upregulation of expression on these cells of chemokine receptor such as CX3CR1 and CCR7, which may lead to the migration of blood monocytes to inflammed tissues and/or secondary lymphoid organs respectively in vivo. There, contact with T cells would lead to the acquisition of antigen presenting function and skewing from tolerogenic to immunogenic responses
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
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