1,721,194 research outputs found
Biophysical study of the human telomeric quadruplexes-drugs interaction: a good starting point for anti cancer agents
No full textXanthene and Xanthone Derivates as G-quadruplex Stabilizing Ligands: ESI-MS and FRET Studies on G-quadruplex Forming Oligonucleotides
No full textXanthene and xanthone derivates as G-quadruplex stabilizing ligands: ESI-MS and FRET studies on oligonucleotides G-quadruplex forming sequences.
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The effect of oxidation on the stability of G-quadruplex DNA : implications for oncogene expression
Full text linkG-quadruplexes (G4-DNA) are a class of secondary structures formed from Guanine rich sequences. In recent years these structures have been implicated in both telomere maintenance and oncogene expression, and have been shown to be abundant in upstream promoter regions and at telomeric ends.
The mutagenic properties of oxidative stress on DNA have been widely studied, as has the association with carcinogenesis. The oxidation of deoxyguanosine to 8-oxo-2’deoxyguanosine (8-oxo-dG) is the most common result when DNA is under oxidative stress and as such, the G-rich sequences that form G-quadruplexes can be viewed as potential “hot-spots” for DNA oxidation. We propose that oxidation may destabilise the G-quadruplex structure, leading to its unfolding into the duplex structure, affecting gene expression. This would imply a possible mechanism by which oxidation may impact on oncogene expression.
This project used both in silico and in vitro methods to observe the effect of oxidation on the G-quadruplex structure and the consequences in oncogene expression, using two biologically relevant G-quadruplex structures, those found in the promoter regions of the proto-oncogenes c-Myc and c-Kit as proof of concept.
Molecular dynamics (MD) simulations were performed (isothermic, isobaric 500ns unrestrained simulation in explicit solvent and counterions) on the c-Kit and c-Myc G-quadruplex structures with and without 8-oxo-dG incorporated into the central tetrad. FRET experiments were performed on these same structures, observing the conformation of sequences known to form G-quadruplexes under near physiological conditions and subjected to oxidative stress, through Fenton chemistry. Gene expression data analyses were also performed to evaluate the prevalence of different G-quadruplex forming motifs (GQMs) in genes affected by oxidation.Although no relevant information was gained from the FRET experiments, the MD results constitute the longest simulations of this type performed on the c-Myc and c-Kit G-quadruplex structures published to date and predict the high stability of these structures under normal physiological conditions. They also clearly demonstrate a destabilising effect of oxidation on G-quadruplex structures, with the extent of the effect dependent on the structure oxidised.
Furthermore, gene expression data analysis showed that genes whose expression is significantly altered when subjected to oxidative stress are statisticallymore likely to contain a GQM than the remainder of the genome, through the use of significance testing.
These findings demonstrate a differential effect of oxidation on G-quadruplexes, likely dependent on other known characteristics affecting G4 stability such as loop length and sequence. Results also point towards this mechanism affecting gene expression. This is suggestive of a novel route for oxidation mediated carcinogenesis, through upregulation of oncogene expression or possibly downregulation of tumour suppression genes
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
Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands
No full textFollowing previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric “bridged” form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data
Natural and synthetic G-quadruplex interactive berberine derivatives
No full textThe interaction of the natural alkaloid berberine with various G-quadruplex DNA structures and its ability to inhibit telomerase have been examined and compared with those of a synthetic piperidino derivative and the related compound coralyne. The results show that these molecules have selectivity for G-quadruplex compared to duplex DNA, and that their aromatic moieties play a dominant role in quadruplex binding. (C) 2005 Elsevier Ltd. All rights reserved
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
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