1,720,966 research outputs found
AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction
No full textEndothelial Retargeting of AAV9 In Vivo
No full textEuropean Research Council https://doi.org/10.13039/501100000781Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
From epidemiology to function
Get PDFArterial hypertension is the most prevalent risk factor for cardiovascular disorders. Most cases of hypertension are due to unknown etiology, with only 5-15 per cent being secondary effects. Primary aldosteronism (PA) is the single most prevalent form of secondary hypertension, and is defined by autonomous aldosterone secretion independent of the plasma renin activity. Routine usage of aldosterone to renin ratio (ARR) for screening PA has revealed greater prevalence of the disorder, especially in resistant or advanced forms of arterial hypertension. The two most common causes of PA are aldosterone producing adenomas (APA) and bilateral adrenal hyperplasia (BAH). Rare Mendelian forms of familial hyperaldosteronism are also described. Until recently, genetic background of only glucocorticoid-remediable familial PA was elucidated in detail. Utilization of the exome sequencing techniques since 2011 identified somatic mutations in the cation transporter genes KCNJ5, ATP1A1, ATP2B3 and CACNA1D as the causative factors for circa 50 % of APAs. The underlying genetic causes of BAH cases remain to be determined.
Genome-wide association studies (GWAS) have been the predominant methodology in genetic epidemiological research in the past ten years, under the hypothesis of “common disease – common variant”. Its prevalent application identified many risk loci, containing targets for functional investigation. In this study ARR was used as a phenotypic parameter in a GWAS in the German KORA-F4 cohort of 1876 individuals, leading to genome-wide significance of a locus in chromosome 5q32. The four genes in this locus (SLC26A2, TIGD6, HMGXB3 and CSF1R) were evaluated by their known characteristics and functions, and functional studies investigating their relevance to aldosterone biosynthesis and function were carried out for SLC26A2 and CSF1R. SLC26A2, a ubiquitously expressed solute carrier with mainly sulfate, oxalate and chloride affinities, was found to be co-regulated with aldosterone production in vivo and in vitro. RNA interference in a model adrenocortical cell line resulted in significantly higher rate of aldosterone production and aldosterone synthase expression, as well as increased overall steroidogenic capacity. Subsequent studies identified calcium signaling dependent pathways as the mediator of this effect. A germline SLC26A2 knock-in mouse model also showed confirmatory endocrine and adrenal phenotype in a sex-specific manner, with elevated plasma aldosterone concentration and ARR in females. The evidence derived from these findings suggests a possible role of SLC26A2 function in the pathophysiology of PA, which requires further epidemiological and functional experiments to confirm and elucidate.Die arterielle Hypertonie gilt als wichtigster Risikofaktor für kardiovaskuläre Erkrankungen. Während in den meisten Fällen eine essentielle Hypertonie angenommen werden kann, liegt in 5-15 % der Patienten dem Bluthochdruck eine andere Erkrankung zugrunde. Mit dem Einsatz des Aldosteron-Renin-Quotienten (ARQ) konnte der primäre Hyperaldosteronismus als die häufigste Form des sekundären Bluthochdrucks eingeordnet werden. Die beiden häufigsten Ursachen des primären Hyperaldosteronismus sind das Aldosteron-produzierende Adenom (APA) und die beidseitige Nebennierenrindenhyperplasie (BAH). Monogenetische, familiäre Formen sind hingegen insgesamt sehr selten. Mit dem Einsatz moderner Sequenziertechniken konnten seit 2011 somatische Mutationen in Ionenkanälen und Transportern (KCNJ5, ATP1A1, ATP2B3 und CACNA1D) in etwa 50 % der APAs identifiziert werden. Die genetische Ursachen der BAH sind dagegen in der überwiegenden Mehrzahl der Fälle unbekannt.
Unter der “common disease – common variant” Hypothese sind Genomweite Assoziationsstudien (GWAS) in den letzten zehn Jahren zur vorherrschenden Methode der genetischen epidemiologischen Forschung geworden. Ihr weit verbreiteter Einsatz hat zur Identifizierung vieler genetischer Risiko-Loci geführt, die dann funktionellen Untersuchungen zugeführt werden konnten. In der vorliegenden Arbeit wurde der ARQ als phänotypische Parameter in einer GWAS der deutschen KORA-F4 Kohorte von 1.876 Personen verwendet. Hierdurch fand sich eine genomweite Signifikanz eines Locus auf Chromosom 5q32. Die vier in diesem Locus enthaltenen Gene (SLC26A2, TIGD6, HMGXB3 und CSF1R) wurden anhand bekannter Eigenschaften und Funktionen eingeordnet und weitergehende funktionelle Studien für SLC26A2 und CSF1R durchgeführt. Für SLC26A2 – einem Transporter mit bekannten Affinitäten zu Sulfat, Oxalat und Chlorid - konnte in vivo und in vitro eine gemeinsame Regulation der adrenalen Expression mit Aldosteron gefunden werden. Ein knock-down von SCL26A2 in einem in vitro Modell durch siRNA führte zu einer relevanten Erhöhung der Aldosteron-Sekretion und transkriptionellen Veränderungen des Steroidbiosynthese-Apparats. Weitergehenden Untersuchungen identifizierten vor allem Kalzium-abhängige Signalkaskaden als für diesen Effekt ursächliche Mechanismen. In einem Slc26a2 knock-in Mausmodell konnten geschlechtsabhängig ein entsprechender endokriner Phänotyp mit einem erhöhten ARQ nachgewiesen werden. Zusammengenommen ergeben sich aus diesen Untersuchungen gute Hinweise für einen Einfluss von SLC26A2 in der Regulation der Aldosteronsekretion und in der Pathophysiologie des primären Hyperaldosteronismus. Weitere funktionelle, epidemiologische und genetische Untersuchungen werden notwendig sein, diese Ergebnisse weiter zu vertiefen und in ihrer potentiellen klinischen Wertigkeit einzuordnen
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
Appropriate 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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