1,721,007 research outputs found
TNFalpha inhibits skeletal myogenesis through a PW1-dependent pathway by recruitment of caspase pathways
No full textCachexia is associated with poor prognosis in patients with chronic disease. Tumor necrosis factor-alpha (TNFalpha) plays a pivotal role in mediating cachexia and has been demonstrated to inhibit skeletal muscle differentiation in vitro. It has been proposed that TNFalpha-mediated activation of NFkappaB leads to down regulation of MyoD, however the mechanisms underlying TNFalpha effects on skeletal muscle remain poorly understood. We report here a novel pathway by which TNFalpha inhibits muscle differentiation through activation of caspases in the absence of apoptosis. TNFalpha-mediated caspase activation and block of differentiation are dependent upon the expression of PW1, but occur independently of NFkappaB activation. PW1 has been implicated previously in p53-mediated cell death and can induce bax translocation to the mitochondria. We show that bax-deficient myoblasts do not activate caspases and differentiate in the presence of TNFalpha, highlighting a role for bax-dependent caspase activation in mediating TNFalpha effects. Taken together, our data reveal that TNFalpha inhibits myogenesis by recruiting components of apoptotic pathways through PW1
Tumor necrosis factor-alpha gene transfer induces cachexia and inhibits muscle regeneration.
No full textChronic disease states are associated with elevated levels of inflammatory cytokines that have been demonstrated to lead to severe muscle wasting. A mechanistic understanding of muscle wasting is hampered by limited in vivo cytokine models which can be applied to emerging mouse mutants as they are generated. We developed a simple and novel approach to
induce adult mouse skeletal muscle wasting based on direct gene transfer of an expression vector encoding the secreted form of the murine tumor necrosis factor-alpha (mTNFa). This procedure results in the production of elevated levels of circulating mTNFa followed by body weight loss, upregulation of Atrogin1, and muscle atrophy, including muscles distant from the site of gene transfer. We also found that mTNFa gene transfer resulted in a significant inhibition of regeneration following muscle injury. We conclude that in addition to being a potent inducer of cachexia, TNFa is a potent inhibitor of myogenesis in viv
STUDY ON THE BPV-INDUCED REPROGRAMMING OF GENE EXPRESSION IN PRIMARY PURIFIED MUSCLE-DERIVED CELLS.
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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
TNF-alpha and AVP differentially affect skeletal muscle regeneration: regulatory role of caspases.
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