1,720,957 research outputs found
TRF2 negatively regulates nucleosome density and organization at human telomeres
No full textTelomeres are the nucleoproteic structures that protect the ends of eukaryotic chromosomes from recombination and degradation. In humans, telomeres consist of several kbp of TTAGGG repeats ending in single-stranded 3’ ends about 150 nt long. Telomeres progressively shorten in replicating cells, as a consequence of end processing and of incomplete DNA replication at chromosome termini, till they reach a critical length that leads to cellular senescence. In germ line cells telomere loss is counteracted by the reverse transcriptase enzyme telomerase, which adds telomeric repeats to the 3’ ends of the chromosomes using as template its RNA moiety. Two hallmarks of cancer can be directly referred to telomeres. First, shortening and/or uncapping of telomeres is one of the main sources leading to the chromosome instability commonly found in cancer. Secondly, in tumors the limitless replicative potential is directly linked to the reactivation of telomerase, or to alternative mechanisms of telomere maintenance.
At the moment, a satisfactory description of telomere organization is still lacking. Double-stranded TTAGGG repeats are organized in tightly spaced nucleosomes and are bound by the specific proteins TRF1 and TRF2, essential for chromosome protection. An unresolved question in the organization of mammalian telomeres is whether specific telomeric proteins compete with the histone octamer for binding to telomeric sequences or whether they cooperate to form a telomeric protective structure. By means of in vitro model systems we previously demonstrated that TRF1 is able to recognize nucleosomal binding sites and to alter nucleosome structure. We show that, unlike TRF1, TRF2 is unable to bind to nucleosomal binding sites, suggesting that TRF2 and the histone octamer compete for binding to telomeres. To investigate how TRF2 interplays with telomeric nucleosomes, we overexpressed TRF2 or a dominant negative mutant in C33A cells by transient lentiviral expression. By means of ChIP analysis and MNase digestion assay we found that the density of nucleosomes at telomeres is inversely correlated with TRF2 dosage. These results are in agreement with in vitro assembly of telomeric nucleosomal arrays by using Drosophila embryonic extracts. Remarkably, when added to the Drosophila extracts TRF2 increases nucleosomal repeat length from 155±5 bp to about 195±5 bp, indicating that TRF2 may preferentially position between nucleosomes. The implication of these findings for telomere stability will be discussed
TRF2 NEGATIVELY AFFECTS NUCLEOSOME ASSEMBLY ON TELOMERIC SEQUENCES
No full textAn unresolved question in the organization of mammalian telomeres is whether specific telomeric proteins compete with the histone octamer for binding to telomeric sequences or whether they cooperate to form a telomeric protective structure. By means of in vitro model systems we previously demonstrated that TRF1 is able to recognize nucleosomal binding sites and to alter nucleosome structure. We show that, unlike TRF1, TRF2 is unable to bind to nucleosomal binding sites, suggesting that TRF2 and the histone octamer compete for binding to telomeres. To investigate how TRF2 interplays with telomeric nucleosomes, we set up a model system to assemble telomeric nucleosomal arrays by using Drosophila embryonic extracts. We found that telomeric nucleosomes are spaced every 155±5 bp, indicating that the short nucleosomal spacing found in vivo is a sequence-dependent feature. Remarkably, when added to the Drosophila extracts TRF2 increases nucleosomal repeat length to about 195±5 bp, indicating that TRF2 may preferentially position between nucleosomes
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
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
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