1,720,965 research outputs found
Transcriptional regulatory circuits involved in the inflammatory response : an unexpected role for the histone demethylase Jarid1b in cholesterol metabolism in macrophages
No full textUNRAVELLING THE ROLE OF THE HISTONE DEMETHYLASE JARID1B IN MACROPHAGES
Full text linkInflammation is a fundamental response to the loss of cellular and tissue homeostasis with many important physiological roles, including host defence, tissue remodelling and repair, and the regulation of metabolism. Macrophages are not only crucial mediators of the inflammatory response, but they are also able to integrate lipid metabolism and inflammatory signalling. After an inflammatory stimulus, the expression of several hundred genes is either induced or repressed in macrophages. This complex transcriptional response consists of multiple transcriptional modules that encode different functional programmes and that are controlled by dedicated transcription factors.
Post-translational modifications of histones are important determinants of transcriptional activity, and it has become evident that many chromatin modifications are extremely dynamic also in response to environmental stimuli. Among these, trimethylation of H3K4 is well conserved during evolution, and is usually associated with the 5’ ends of actively transcribed or “poised” genes.
Although in the last decades the signalling pathways leading to the activation of an inflammatory response have been very well characterized, the knowledge about the tuning of this complex transcriptional network is still limited.
Using a candidate approach we demonstrated that Jarid1b is transcriptionally up-regulated with a slow kinetics by LPS stimulation under the control of the transcription factor Hif1.
Jarid1b is a member of the JARID1 family of H3K4 demethylases, and it has been proposed to act as transcriptional repressor, with a putative role in cell proliferation.
Depletion experiments in primary macrophages suggested that Jarid1b is necessary for the activation of the master regulator of cholesterol metabolism, LXR, and the expression of its target genes, likely through the control of cellular oxysterols pools.
We also generated Jarid1b knock-out mice, and performed global expression analysis in Jarid1b-deficient macrophages. The obtained data together with genomic binding analyses showed a very limited transcriptional regulatory function for Jarid1b in this cellular system. We also collected preliminary data on a possible role for Jarid1b, independent of its reported histone demethylase enzymatic activity, in regulating RNA methylation levels
The histone demethylase Jarid1b as a component of transcriptional regulatory circuits involved in the inflammatory response
No full text
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
The histone H3 lysine 27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing
No full textEpigenetic chromatin marks restrict the ability of differentiated cells to change gene expression programs in response to environmental cues and to transdifferentiate. Polycomb group (PcG) proteins mediate gene silencing and repress transdifferentiation in a manner dependent on histone H3 lysine 27 trimethylation (H3K27me3). However, macrophages migrated into inflamed tissues can transdifferentiate, but it is unknown whether inflammation alters PcG-dependent silencing. Here we show that the JmjC-domain protein Jmjd3 is a H3K27me demethylase expressed in macrophages in response to bacterial products and inflammatory cytokines. Jmjd3 binds PcG target genes and regulates their H3K27me3 levels and transcriptional activity. The discovery of an inducible enzyme that erases a histone mark controlling differentiation and cell identity provides a link between inflammation and reprogramming of the epigenome, which could be the basis for macrophage plasticity and might explain the differentiation abnormalities in chronic inflammation
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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