1,721,638 research outputs found

    Proteotoxicity: an underappreciated pathology in cardiac disease.

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    In general, in most organ systems, intracellular protein homeostasis is the sum of many factors, including chromosomal state, protein synthesis, post-translational processing and transport, folding, assembly and disassembly into macromolecular complexes, protein stability and clearance. In the heart, there has been a focus on the gene programs that are activated during pathogenic processes, but the removal of damaged proteins and organelles has been underappreciated as playing an important role in the pathogenesis of heart disease. Proteotoxicity refers to the adverse effects of damaged or misfolded proteins and even organelles on the cell. At the cellular level, the ultimate outcome of uncontrolled or severe proteotoxicity is cell death; hence, the pathogenic impact of proteotoxicity is maximally manifested in organs with no or very poor regenerative capability such as the brain and the heart. Evidence for increased cardiac proteotoxicity is rapidly mounting for a large subset of congenital and acquired human heart disease. Studies carried out in animal models and in cell culture have begun to establish both sufficiency and, in some cases, the necessity of proteotoxicity as a major pathogenic factor in the heart. This dictates rigorous testing for the efficacy of proteotoxic attenuation as a new strategy to treat heart disease. This review article highlights some recent advances in our understanding of how misfolded proteins can injure and are handled in the cell, examining the emerging evidence for targeting proteotoxicity as a new therapeutic strategy for heart diseas

    Nino Salvatore's contribution to scientific collaboration between Europe and the US in endocrinology.

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    The Authors describe in this guest editorial the relevance that Gaetano ("Nino") Salvatore had in promoting science and international collaboration between Europe and the US. He also encouraged links between cellular and molecular biology, producing important advances in both technology and ideas. His group devised the FRT-L system of rat thyroid cells that carry out in vitro all the differentiated functions of the thyroid gland; this system is now used worldwide. The diverse approaches he encouraged were instrumental in the discovery of rearrangements in the RET proto-oncogene in papillary thyroid cancer and in elucidating the role of genes encoding transcription factors in the early development of the thyroid gland and in congenital thyroid dysfunction. Both discoveries, derived from basic research, have proved important in clinical endocrinology

    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
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