1,720,958 research outputs found
Targeting hTERT core promoter with specific G-quadruplex ligands
In mammalian somatic cells telomeres shorten at each replication till they reach a critical length that leads to cell replicative senescence. Cancer cells overcome this limit by acquiring the capability to maintain functional telomeres. In most cases, this is due to upregulation of the expression of hTERT, encoding the proteic moiety of telomerase. Therefore, several anti-cancer strategies that target telomerase activity and hTERT expression are being developed. One of these strategies is based on ligands that induce the formation of a G-quadruplex structure at the ends of chromosomes, thus preventing telomerase elongation.
Recently, it has been reported that the hTERT core promoter contains a G-rich region able to form multiple G-quadruplex structures, representing a possible target for G-quadruplex ligands. By means of circular dichroism (CD) spectroscopy and DNA polymerase stop assay we report that a series of perylene derivatives with different hydrophilic side chains (HPDIs, hydrosoluble perylene diimides) are able to specifically stabilize G-quadruplex structures and superstructures on the hTERT promoter and to inhibit DNA replication. These data suggest that ligand-induced G-quadruplex formation on hTERT promoter could affect hTERT expression. An analysis of HPDIs effect on hTERT promoter activity by luciferase reporter assay is in progress.
An attractive hypothesis is that G-quadruplex ligands could inhibit telomerase activity not only by targeting the terminal telomeric G-tails but also by inducing G-quadruplex structures on the hTERT promoter
G-quadruplex superstructure in the hTERT core promoter: stabilization by monomer self-stacking
G-quadruplex-forming are widespread in eukaryotic genomes. In particular, G-quadruplex motifs have been found in the promoter region of 40% human genes. One of these genes is hTERT, encoding the catalytic subunit of human telomerase, whose up-regulated expression is responsible for the unlimited proliferative potential of most cancer cells. hTERT core promoter exhibits a high potential for G-quadruplex formation, containing nine partially overlapping PQS (putative quadruplex sequence) in a G-rich region of 68 nucleotides. Here we show the formation of a superstructure in the hTERT promoter deriving from the simultaneous folding of three adjacent G-quadruplex structures. Interestingly, G-quadruplex ligands are able to stabilize hTERT G-quadruplex structures and to alter transcription from the hTERT promoter, suggesting that the formation of a G-quadruplex superstructure could play a role in regulating gene transcription
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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