1,721,216 research outputs found

    EXPLOITING VASOPRESSIN SIGNALLING IN MUSCULAR ATROPHY AND DYSTROPHIES

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    This study aims to evaluate the effects of the stimulation of the AVP-dependent pathways on muscular atrophy. Arg-vasopressin (AVP) has been demonstrated to have a potent effect as myogenic promoting factor both in vitro and in vivo. In skeletal muscle AVP signaling is mediated by the V1a receptor, whose stimulation results in the activation of PLC and PLD, increased cytosolic calcium concentration and stimulation of CaMK (Ca2+/calmodulin-dependent protein kinase) and calcineurin pathways, leading to the formation of multifactor complexes on the promoter of muscle specific genes, thus activating their transcription. In this study we induced muscular atrophy by local over-expression of TNF and we evaluated the effects of the stimulation of AVP signaling pathways in this condition by over-expressing V1a receptor. TNF is a pro-inflammatory cytokine and it is known to inhibit myogenic differentiation both in vitro and in vivo, and we have previously demonstrated that the negative effects of TNF in vitro is counteracted by AVP treatment. Moreover it has been demonstrated that TNF plays a key role in the activation of the inflammatory pathways mediated by NF-kB and in the stimulation of protein catabolism. For these reasons, we evaluated, in TNF-expressing muscle, the effects of V1aR over-expression in the regeneration process, in the inflammatory status and in protein degradation. Morphological and morphometric analysis demonstrated that the local over-expression of V1aR in the atrophic muscle enhances the cross-sectional area of the regenerating fibers. Since we noted the presence of infiltrating mono-nucleated cells in muscles over-expressing TNF, we investigated the nature of the infiltrate: it is positive for esterase activity, demonstrating the presence of macrophages. Esterase activity is reduced in muscles over-expressing both TNF and V1aR. We further demonstrated that the up-regulation of NF-kB expression by TNF is reduced by the contemporary over-expression of V1aR. We noted a prevalence of chemokines and cytokines specific of the pro-inflammatory phenotype of macrophages (M1) in the presence of TNF, but an increased levels of antigens and anti-inflammatory cytokines specific for M2 macrophage phenotype in muscle over-expressing both TNF and V1aR. In regards to the regenerative process, the expression levels of early regeneration markers, such as Pax7 and desmin, are up-regulated by TNF, whereas late differentiation markers, such as myogenin and MHC, are down-regulated. The simultaneous over-expression of V1aR up-regulates the expression of both early and late differentiation markers. These data demonstrate that the stimulation of AVP-dependent pathways enhances skeletal muscle regeneration. We also analyzed PI3K/Akt pathway because TNF is known to induce protein degradation. V1 over-expression maintains the phosphorylation levels of Akt and FoxO, at least inhibiting atrogin-1 transcription activated by TNF, thus counteracting protein degradation. According to these results we are extending our studies to the effects of AVP signaling in muscular dystrophies. Very preliminary data suggest a positive role of AVP even in dystrophic muscles in mdx and Scgβ-null mice, though technical issues have yet to be solved

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Exploiting Vasopressin signaling in muscular atrophy and dystrophies

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    Arginine-Vasopressin (AVP) is a neurohypophyseal hormone able to induce differentiation in myogenic cell lines and primary satellite cells. V1aR is the only AVP receptor expressed in skeletal muscle. By interacting with V1aR, AVP activates phospholipases C and D, increases cytosolic Ca2+ concentrations and regulates cAMP levels. The AVP-dependent increase in cytosolic calcium activates CaMK and calcineurin pathways resulting in the formation of multifactor complexes on the promoter of muscle specific genes. Our previous data demonstrate that V1aR expression is modulated during muscle regeneration and the stimulation of AVP signaling strongly enhances regeneration of injured muscles. In an experimental model of muscular atrophy induced by TNF over-expression, stimulation of AVP pathways counteracts the negative effects of TNF both enhancing regeneration and inhibiting inflammation. The molecular analysis for the expression levels of early and late regeneration markers (Pax7 and MyoD or myogenin and MHC, respectively) suggested an impairment of regeneration in muscles over-expressing TNF. This effect was counteracted by V1aR overexpression. The positive effects of V1aR on muscle homeostasis are due to the promotion of the calcinuerin-IL-4 pathway and by the inhibition of atrophic genes expression mediated by FOXO phosphorylation via Akt-dependant pathway. By all the above we are analyzing the effects of AVP signaling stimulation in mouse models of muscular dystrophies. Preliminary data demonstrate that stimulation of AVP-dependent pathways ameliorates inflammation and regeneration processes. This study highlights a novel in vivo role for the AVP-dependent pathways which may represent a potential gene therapy approach for many diseases affecting muscle homeostasis

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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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