1,720,996 research outputs found
QUADRatlas: the RNA G-quadruplex and RG4-binding proteins database
Full text linkRNA G-quadruplexes (RG4s) are non-canonical, disease-associated post-transcriptional regulators of gene expression whose functions are driven by RNA-binding proteins (RBPs). Being able to explore transcriptome-wide RG4 formation and interaction with RBPs is thus paramount to understanding how they are regulated and exploiting them as potential therapeutic targets. Towards this goal, we present QUADRatlas (https://rg4db.cibio.unitn.it), a database of experimentally-derived and computationally predicted RG4s in the human transcriptome, enriched with biological function and disease associations. As RBPs are key to their function, we mined known interactions of RG4s with such proteins, complemented with an extensive RBP binding sites dataset. Users can thus intersect RG4s with their potential regulators and effectors, enabling the formulation of novel hypotheses on RG4 regulation, function and pathogenicity. To support this capability, we provide analysis tools for predicting whether an RBP can bind RG4s, RG4 enrichment in a gene set, and de novo RG4 prediction. Genome-browser and table views allow exploring, filtering, and downloading the data quickly for individual genes and in batch. QUADRatlas is a significant step forward in our ability to understand the biology of RG4s, offering unmatched data content and enabling the integrated analysis of RG4s and their interactions with RBPs
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
Protein synthesis control in cancer: focus on non-canonical regulators
No full textInternational audienc
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
Role of the DNA repair protein Ku in the translational regulation of p53 mRNA
No full textL'augmentation des taux cellulaires de p53 en réponse aux dommages à l'ADN a été largement attribuée à une augmentation de la demi-vie de la protéine. Il est maintenant bien établi que la régulation traductionnelle de l'ARNm de p53 est également critique à la fois pour la répression de l'accumulation de p53 dans des conditions normales, et l'induction de la protéine en réponse aux dommages de l'ADN. Nos travaux se sont accès sur l'étude du rôle de facteur de réparation de l'ADN Ku dans la régulation traductionnelle de l'ARNm P53. Nous avons montré que Ku réprime la synthèse de la protéine p53 et l'apoptose p53-dépendante via la liaison à une structure en tige-boucle dans la 5'UTR de l'ARNm. Cependant, la répression traductionnelle exercée par Ku est levée après un stress génotoxique. Le mécanisme sous-jacent implique l'acétylation de Ku qui perturbe les interactions Ku-ARNm p53. Ces résultats suggèrent que la répression traductionnelle de p53 par Ku constitue un nouveau mécanisme cytoprotectif liant la réparation de l'ADN et la traduction des ARNm.Increases in p53 protein levels after DNA damage have largely been attributed to an increase in the half-life of the p53 protein. It is now well accepted that translational regulation of p53 mRNA is also critical for both repression of p53 accumulation in unstressed conditions and induction of the p53 protein in response to DNA damage. Our work focused on studying the role of DNA repair factor Ku in the regulation of P53 mRNA translation. We showed that Ku represses p53 protein synthesis and p53-mediated apoptosis by binding to a stem-loop structure within the p53 5'UTR. However, Ku-mediated translational repression is relieved after genotoxic stress. The underlying mechanism involves Ku acetylation which disrupts Ku-p53 mRNA interactions. These results suggest that Ku-mediated repression of p53 mRNA translation constitutes a novel cytoprotective mechanism linking DNA repair and mRNA translation
Role and mechanisms of RNA G-quadruplexes in mitochondrial protein synthesis and function
No full textContrairement à ce qui a précédemment été admis, les cellules cancéreuses reposent sur la mitochondrie comme source d’énergie et pour la production de macromolécules. La régulation de la synthèse des protéines mitochondriales se trouve au cœur de la fonction mitochondriale. Elle dépend principalement de la traduction cytosolique des ARNm codés par le noyau dont les protéines sont importées dans la mitochondrie. Malgré la prise de conscience croissante que la synthèse des protéines mitochondriales contribue à l'apparition et à la progression du cancer, offrant ainsi de nouvelles opportunités de traitements, les mécanismes moléculaires sous-jacents restent peu explorés. Mon projet de thèse visait à mieux caractériser les déterminants liant la synthèse protéique et la fonction mitochondriale en me concentrant sur les G-quadruplexes ARN (RG4), des structures d'ARN dynamiques qui ont gagné de l’importance dans la biologie de l’ARN et les maladies associées. Nos travaux ont contribué au concept dans lequel les RG4 et leurs partenaires protéiques (i.e. les protéines de liaison à l’ARN) jouent un rôle clé dans la régulation traductionnelle des ARNm codant pour des facteurs essentiels au développement tumoral et à la résistance aux traitements. Sur la base d’études récentes soutenant l’implication des RG4 dans l'expression des gènes mitochondriaux, nous avons émis l'hypothèse que ces structures contrôlent l'expression des ARNm mitochondriaux, participant ainsi à la reprogrammation métabolique mitochondriale nécessaire à la croissance néoplasique. Nous avons montré que les RG4 sont localisés à la mitochondrie et qu’ils régulent les fonctions mitochondriales en modulant la traduction cytosolique d’ARNm mitochondriaux codés par le noyau. Nous avons identifié la protéine de liaison à l’ARN hnRNP U comme nouveau régulateur de la traduction d’ARNm mitochondriaux qui contiennent des RG4. Nos résultats soutiennent un modèle dans lequel la stabilisation des RG4, avec des ligands ou par la diminution de l’expression de hnRNP U, modifie la synthèse des protéines mitochondriales codées par le noyau, ce qui entraîne une diminution des fonctions mitochondriales affectant alors le métabolisme énergétique et, par conséquent, la prolifération des cellules cancéreuses. Ces données pourraient ouvrir la voie à de futures stratégies pour affecter les fonctions mitochondriales liées à la croissance tumorale en ciblant la traduction mitochondriale par la modulation des interactions RG4-protéine ou la structuration des RG4.)Contrary to the conventional wisdom, cancer cells rely on the mitochondria for their bioenergetic machinery and macromolecule synthesis. Central to mitochondrial function is the regulation of the synthesis of mitochondrial proteins, which depends primarily on the cytosolic translation of nuclear-encoded mitochondrial mRNAs whose protein products are imported into mitochondria. Despite the growing awareness that mitochondrial protein synthesis contributes to the onset and progression of cancer and offers new opportunities for cancer therapy, the underlying molecular mechanisms remain underexplored. My PhD thesis project aimed at better characterizing the determinants linking protein synthesis and mitochondrial function by focusing on RNA G-quadruplexes (RG4s), dynamic RNA structures that have gained growing importance in RNA biology and disease. Our work contributed to the notion that RG4s together with their protein partners (i.e. RNA-binding proteins) play a key role in translational regulation of mRNA encoding factors critical for tumor development and treatment resistance. Based on recent evidence supporting a role for RG4s in mitochondrial gene expression, we hypothesized that these structures drive the expression of mitochondrial mRNAs, thus controlling the mitochondrial metabolic reprogramming required for neoplastic growth. Here, we showed that RG4s are localized to mitochondria and control mitochondrial functions by modulating the cytosolic mRNA translation of nuclear-encoded mitochondrial proteins. We identified the RNA-binding protein hnRNP U as new regulator of mitochondrial translation of RG4-containing mRNAs. Our results support a model whereby RG4 stabilization, induced by small molecule ligands or by depleting hnRNP U, alters nuclear-encoded mitochondrial mRNA protein synthesis, resulting in a decrease in mitochondrial functions affecting energy metabolism and consequently cancer cell proliferation. These data may pave the way for future strategies to rewire mitochondrial functions related to tumor growth by targeting mitochondrial translation through modulation of RG4-protein interactions or RG4 structuration
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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