1,720,966 research outputs found
NOVEL FUNCTIONS OF POLYCOMB PROTEINS AND OGT GLYCOSYLTRANSFERASEIN CHROMATIN REGULATION AND TRANSCRIPTION CONTROL IN EMBRYONIC STEM CELLS
During my PhD course, I have been involved in studies aiming to identify novel properties of proteins having fundamental roles in the regulation of chromatin modifications and gene transcription.
One of the two project was focused on the functional characterization of the products of the catalytic activity of Polycomb Repressive Complex 2 (PRC2). In spite of the wide knowledge about PRC2-dependent trimethylation of Lysine 27 of histone H3 (H3K27me3), the other forms of methylation on H3K27, namely mono (me1) and di-methylation (me2), are still poorly characterized. Using mouse embryonic stem cells (mESC) as model system, we were able to provide an extensive characterization of the functional properties of these methylation forms, highlighting their differential deposition along the genome, their fundamental role in the mechanisms of transcriptional regulation in mESC, and their potential implications during differentiation program. Our data demonstrated that while H3K27me1 was required for efficient transcription of genes and positively correlated with the deposition of H3K36me3, H3K27me2 was broadly deposited and protects the genome from aberrant firing of non specific cell type enhancers.
My second project focused on the activity of the O-linked glycosyltransferase Ogt which is the only enzyme capable to catalyze O-linked GlcNAcylation within the cell. Sxc protein, which is the Drosophila orthologue of mammalian Ogt, is essential for Polycomb (PcG) function. Sxc null embryos showed lethal phenotypes at early developmental stages like those observed in PcG null embryos. Starting from this observation we found appealing to investigate whether Sxc function in Drosophila were conserved in mammals. In particular, we were interested in the discovery of possible role for Ogt in the context of PcG recruitment to chromatin and the mechanisms governing transcriptional regulation in mESC. With our study we have identified a novel partnership between Ogt and ten-eleven translocation (TET) proteins, which catalyze hydroxylation of methylated cytosine. We have shown that Tet1 protein recruits Ogt to target genes in proximity of transcription start sites (TSS) rich in cytosine-guanine dinucleotides (CpG). Tet1-Ogt co-localization at target genes correlated with low levels of cytosine modification, suggesting a role in the regulation of CpG island (CpGi) methylation
The controversial role of the Polycomb group proteins in transcription and cancer : how much do we not understand Polycomb proteins?
Polycomb group proteins (PcGs) are a large protein family that includes diverse biochemical features assembled together in two large multiprotein complexes. These complexes maintain gene transcriptional repression in a cell type specific manner by modifying the surrounding chromatin to control development, differentiation and cell proliferation. PcGs are also involved in several diseases. PcGs are often directly or indirectly implicated in cancer development for which they have been proposed as potential targets for cancer therapeutic strategies. However, in the last few years a series of discoveries about the basic properties of PcGs and the identification of specific genetic alterations affecting specific Polycomb proteins in different tumours have converged to challenge old dogmas about PcG biological and molecular functions. In this review, we analyse these new data in the context of the old knowledge, highlighting the controversies and providing new models of interpretation and ideas that will perhaps bring some order among apparently contradicting observations. Polycomb group proteins (PcGs) assemble two large complexes with different biochemical features ensuring gene transcriptional repression in a cell-type specific manner by modifying the surrounding chromatin. PcGs control development, differentiation, cell proliferation and are involved in cancer onset. This review analyzes new evidences challenging old dogmas about PcG functions, highlighting the controversies and providing new models to interpret PcG activities
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
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