1,720,955 research outputs found
New mechanisms underlying the variable phenotypes caused by N- and C-terminal mutations in the cardiac sodium channel
No full textLes mutations du gène SCN5A, codant la sous-unité ? du canal Na+ cardiaque Nav1.5, sont responsables d'arythmies cardiaques héréditaires. La pénétrance incomplète observée dans ces maladies suggère l'existence d'autres facteurs modulant le phénotype associé à ces mutations. Dans ce travail de thèse, nous avons caractérisé deux mutations identifiées dans SCN5A. Le mutant R104W, identifié chez un patient atteint du syndrome de Brugada, est retenu dans le réticulum endoplasmique (RE), dégradé par le protéasome et abolit le courant Na+. Co-exprimé avec le canal sauvage, R104W conduit à la rétention de celui-ci dans le RE, résultant en un effet dominant négatif sur les canaux sauvages. Nous avons démontré que ce nouveau mécanisme mettait en jeu une interaction entre les sous-unités ? de Nav1.5. La mutation R1860Gfs*12 a été identifiée dans une famille présentant des arythmies auriculaires. Dans un système d'expression hétérologue, ce mutant induit à la fois une perte et un gain de fonction de Nav1.5. La modélisation informatique nous a permis de montrer que la perte de fonction était plus prononcée dans les cellules auriculaires que ventriculaires. De plus, nous avons montré que la présence de polymorphismes en amont du gène PITX2 dans cette famille pouvait expliquer la variabilité des phénotypes observés. En conclusion, l'interaction entre les sous-unités ? de Nav1.5, les propriétés électriques différentes entre oreillette et ventricule et la présence de polymorphismes chez les patients porteurs de mutations SCN5A sont des facteurs importants dans l'interprétation des effets fonctionnels de ces mutations, contribuant à la variabilité phénotypique des canalopathies Na+.Mutations in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Nav1.5, are implicated in different inherited cardiac arrhythmias. The incomplete penetrance observed in these diseases suggests the existence of other factors modulating the phenotype of these mutations. In this thesis work, we characterized two mutations identified in SCN5A. The R104W mutant identified in a patient with Brugada syndrome is retained in the endoplasmic reticulum (ER), degraded by the proteasome and abolishes the sodium current. Co-expressed with wild type (WT) channels, R104W leads to WT channels ER retention, causing a dominant-negative effect. We demonstrated that interaction between Nav1.5 α-subunits is responsible for the retention and the dominant-negative effect. The R1860Gfs*12 mutation was identified in a family with atrial arrhythmias. In a heterologous system, this mutant induces both loss- and gain-of-function effects on Nav1.5. Computer-model simulation showed that the loss-of-function was more pronounced in atrial than in ventricular cells. In addition, we showed that the presence of polymorphisms upstream of the PITX2 gene could explain the observed phenotypic variability in this family. In conclusion, the interaction between the α-subunits of Nav1.5, the different electrical properties between atria and ventricles and the presence of polymorphisms in patients with SCN5A mutations, are important factors in the interpretation of the functional effects of these mutations, which could explain the phenotypic variability of sodium channelopathies
Nouveaux mécanismes contribuant à la variabilité phénotypique de mutations N- et C-terminales du canal sodique cardiaque
No full textMutations in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Nav1.5, are implicated in different inherited cardiac arrhythmias. The incomplete penetrance observed in these diseases suggests the existence of other factors modulating the phenotype of these mutations. In this thesis work, we characterized two mutations identified in SCN5A. The R104W mutant identified in a patient with Brugada syndrome is retained in the endoplasmic reticulum (ER), degraded by the proteasome and abolishes the sodium current. Co-expressed with wild type (WT) channels, R104W leads to WT channels ER retention, causing a dominant-negative effect. We demonstrated that interaction between Nav1.5 α-subunits is responsible for the retention and the dominant-negative effect. The R1860Gfs*12 mutation was identified in a family with atrial arrhythmias. In a heterologous system, this mutant induces both loss- and gain-of-function effects on Nav1.5. Computer-model simulation showed that the loss-of-function was more pronounced in atrial than in ventricular cells. In addition, we showed that the presence of polymorphisms upstream of the PITX2 gene could explain the observed phenotypic variability in this family. In conclusion, the interaction between the α-subunits of Nav1.5, the different electrical properties between atria and ventricles and the presence of polymorphisms in patients with SCN5A mutations, are important factors in the interpretation of the functional effects of these mutations, which could explain the phenotypic variability of sodium channelopathies.Les mutations du gène SCN5A, codant la sous-unité ? du canal Na+ cardiaque Nav1.5, sont responsables d'arythmies cardiaques héréditaires. La pénétrance incomplète observée dans ces maladies suggère l'existence d'autres facteurs modulant le phénotype associé à ces mutations. Dans ce travail de thèse, nous avons caractérisé deux mutations identifiées dans SCN5A. Le mutant R104W, identifié chez un patient atteint du syndrome de Brugada, est retenu dans le réticulum endoplasmique (RE), dégradé par le protéasome et abolit le courant Na+. Co-exprimé avec le canal sauvage, R104W conduit à la rétention de celui-ci dans le RE, résultant en un effet dominant négatif sur les canaux sauvages. Nous avons démontré que ce nouveau mécanisme mettait en jeu une interaction entre les sous-unités ? de Nav1.5. La mutation R1860Gfs*12 a été identifiée dans une famille présentant des arythmies auriculaires. Dans un système d'expression hétérologue, ce mutant induit à la fois une perte et un gain de fonction de Nav1.5. La modélisation informatique nous a permis de montrer que la perte de fonction était plus prononcée dans les cellules auriculaires que ventriculaires. De plus, nous avons montré que la présence de polymorphismes en amont du gène PITX2 dans cette famille pouvait expliquer la variabilité des phénotypes observés. En conclusion, l'interaction entre les sous-unités ? de Nav1.5, les propriétés électriques différentes entre oreillette et ventricule et la présence de polymorphismes chez les patients porteurs de mutations SCN5A sont des facteurs importants dans l'interprétation des effets fonctionnels de ces mutations, contribuant à la variabilité phénotypique des canalopathies Na+
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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