1,720,958 research outputs found

    Role of physical exercise in the UPRmt in skeletal muscle

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    Orientador: Eduardo Rochete RopelleDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências AplicadasResumo: A UPRmt, do inglês mitochondrial unfolded protein response, é uma resposta adaptativa ao estresse, que assegura a integridade e função de proteínas mitocondriais por estimular a atividade de chaperonas (como a HSP60) e proteases mitocondriais (como ClpP). Estudos mutagênicos revelaram que a alteração no equilíbrio estequiométrico entre proteínas codificadas pelo DNA mitocondrial (mtDNA), como a MTCO1, e proteínas da cadeia transportadora de elétrons oriundas do DNA nuclear (nDNA), como SDHA ou ATP5A, ativa a UPRmt. Em organismos como C.elegans e Drosophila, tal resposta aumenta a função mitocondrial, o metabolismo celular e a longevidade através da UPRmt. Tratamentos farmacológicos (como doadores de NAD+ ou ativadores de SIRT1) também ativam esta resposta, aumentando função e biogênese mitocondrial, a capacidade oxidativa de músculo esquelético e fígado, e ainda melhoram sua capacidade funcional. Ainda que a indução da UPRmt mediada pelo desequilíbrio mitonuclear aparentemente seja um processo biológico conservado entre mamíferos, aumentando a função orgânica em diferentes tecidos, ainda não foi explorado se o exercício físico (que aumenta os níveis de NAD+ e ativa SIRT1 e outras vias de biogênese mitocondrial) é capaz de ativar esta resposta ao estresse. Portanto, o objetivo do presente estudo foi avaliar o conteúdo proteico de marcadores da UPRmt e o desequilíbrio mitonuclear no gastrocnêmio de camundongos treinados, bem como sua função mitocondrial. Para tal, foram utilizados camundongos C57BL/6J machos, alocados em grupo controle ou treinado (4 semanas de corrida em esteira). As amostras foram avaliadas por Western-blotting e por respiração mitocondrial. As análises de bioinformática foram realizadas por meio da base de dados genenetwork.org, utilizando dados da musculatura esquelética de linhagens BXD e de humanos. Em camundongos, os marcadores da UPRmt apresentaram forte correlação com genes mitocondriais (também observada na base de dados de humanos) e com fenótipos relacionados à adaptações geradas pelo exercício físico, como RER e atividade locomotora. Os animais treinados aumentaram sua performance, seus níveis de respiração mitocondrial, tiveram aumento de 2 vezes na razão MTCO1:SDHA (desequilíbrio mitonuclear) e aumento do conteúdo proteico de ClpP. Este projeto pode auxiliar na compreensão do papel da UPRmt sobre diversas adaptações desencadeadas pelo exercício físico e na busca por terapias para doenças originadas na disfunção mitocondrialAbstract: The mitochondrial unfolded protein response (UPRmt) is an adaptive stress response, which ensures both integrity and function of proteins by stimulating mitochondrial chaperones (such as HSP60) and mitochondrial proteases (such as ClpP). Mutagenic studies revealed that alterations in the stoichiometric ratio between mtDNA encoded proteins (such as MTCO1) and nDNA OXPHOS subunits of the electron transport chain, such as SDHA or ATP5A, activates the UPRmt. In organisms such as C.elegans and Drosophila, this response enhances mitochondrial function, cell metabolism and longevity through activation of the UPRmt. Pharmacological treatments (such as NAD + boosters or SIRT1 activators) also activate this response, increasing mitochondrial biogenesis and function, oxidative capacity of skeletal muscle and liver and even improves their functional capacity. Although the induction of UPRmt, mediated by mitonuclear imbalance, seems to be a well-conserved biological process among mammals (by increasing the organic function in different tissues), it has not yet been explored if exercise (which increases the NAD+ levels, SIRT1 activity and triggers other pathways promoting mitochondrial biogenesis) is able to activate such stress response. Therefore, the aim of this study was to evaluate the protein content of UPRmt markers and the mitonuclear imbalance in the gastrocnemius of trained mice, as well as mitochondrial function. For this purpose, C57BL/6J mice were allocated into control or trained groups (4 weeks of treadmill running). Skeletal muscle samples were analyzed by Western blotting and mitochondrial respiration. Bioinformatics analysis was performed using genenetwork.org database, with data from skeletal muscle of human and BXD strains. In mice, the UPRmt markers were strongly correlated with mitochondrial genes (also observed in human database) and exercise-related phenotypes, such as RER and locomotor activity. The trained animals increased their exercise performance, their mitochondrial respiration, presented mitonuclear imbalance (2-fold increase in the MTCO1:SDHA ratio) and increased ClpP protein content. This project can assist in understanding the role of UPRmt on several exercise-induced adaptations and provide useful knowledge for future therapies targetting diseases related to mitochondrial dysfunctionMestradoMetabolismo e Biologia MolecularMestre em Ciências da Nutrição e do Esporte e Metabolismo2015/06463-8FAPES

    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

    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

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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