1,720,984 research outputs found
Nadolol block of Nav1.5 does not explain its efficacy in the long QT syndrome.
Get PDFBeta-adrenergic receptor antagonists (β-blockers) are the therapy of choice for the long QT syndrome but their efficacy is not homogeneous: propranolol and nadolol are the most effective, whereas metoprolol is associated with more treatment failures. Propranolol has a blocking effect on the sodium current ("membrane-stabilizing" effect), and it has been hypothesized that the efficacy of nadolol might be due to a similar effect. Accordingly, we used whole-cell patch-clamp recording to assess propranolol, nadolol, and metoprolol block of wild-type or mutant cardiac sodium channels (Nav1.5) coexpressed with β1 subunit in tsA201 cells. Nadolol had a ∼20% non-use-dependent blocking effect on peak sodium current and no effect on the persistent current evoked by the LQT3 mutant A1330D, whereas propranolol blocked Nav1.5 in a use-dependent manner and reduced A1330D persistent current. Metoprolol had no effect on either the peak or persistent current. Analysis of the biophysical properties of the channel revealed that both nadolol and propranolol cause hyperpolarizing shifts on voltage dependence of activation and steady-state inactivation, whereas metoprolol shifts only the activation curve. These results provide partial explanation for the differences between nadolol and metoprolol but do not explain the similar clinical efficacy of nadolol and propranolol
Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type-dependent biophysical and pharmacological properties
No full textATP-sensitive K channels (KATP) are an octameric complex of inwardly rectifying K channels (Kir6.1 and Kir6.2) and sulfonylurea receptors (SUR1 and SUR2AB), which are involved in several diseases. The tissue-selective expression of the subunits leads to different channels; however, the composition and role of the functional channel in native muscle fibers is not known. In this article, the properties of KATP channels of fast-twitch and slowtwitch muscles were compared by combining patch-clamp experiments with measurements of gene expression. We found that the density of KATP currentsarea was muscle-type specific, being higher in fast-twitch muscles compared with the slow-twitch muscle. The density of KATP currentsarea was correlated with the level of Kir6.2 expression. SUR2A was the most abundant subunit expressed in all muscles, whereas the vascular SUR2B subunit was expressed but at lower levels. A significant expression of the pancreatic SUR1 was also found in fast-twitch muscles. Pharmacological experiments showed that the channel response to the SUR1 agonist diazoxide, SUR2AB agonist cromakalim, SUR1 antagonist tolbutamide, and the SUR1SUR2A/B-antagonist glibenclamide matched the SURs expression pattern. Muscle-specific KATP subunit compositions contribute to the physiological performance of different muscle fiber types and determine the pharmacological actions of drugs modulating KATP activity in muscle diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
A KCNH2 branch point mutation causing aberrant splicing contributes to an explanation of genotype-negative long QT syndrome.
No full textAppropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Get PDFWe 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
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