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The role of plakoglobin in adipocyte expansion and obesity
Get PDFL'obésité est actuellement une épidémie mondiale, dont la prévalence augmente chaque année. Généralement définie comme un déséquilibre entre la dépense énergétique et l'apport énergétique, elle constitue une menace sérieuse contre notre société, car elle est associée à un risque accru de développer des maladies chroniques graves comme les maladies cardiovasculaires, le diabète et différents types de cancer. L'excès d'énergie est stocké dans les adipocytes, induisant un remodelage via l'hyperplasie ou l'hypertrophie. Nos connaissances sur les divers mécanismes régulateurs gouvernant l'hyperplasie des adipocytes restent incomplètes. Précédemment, notre laboratoire a défini un rôle pour la protéine d’échafaudage 14-3-3ζ dans l'expansion du tissu adipeux viscéral et l'exacerbation de l'obésité induite par l'alimentation. Une analyse protéomique a révélé l’interactome de 14-3-3ζ au sein du tissu adipeux et a identifié des candidats connus ainsi que de nouveaux régulateurs potentiels de l'adipogenèse. L'un des partenaire potentiel est la plakoglobine, un homologue proche de la β-caténine. L'axe Wnt/β-caténine est connu pour inhiber l'adipogenèse in vitro, orientant les cellules progénitrices vers des destins ostéogéniques. Dans certains contextes, la plakoglobine est capable d'inhiber l'activité transcriptionnelle de Wnt/β-caténine, activant préférentiellement un autre sous-ensemble de gènes cibles. Des preuves de ce phénomène ont été mises en évidence dans des études sur les cardiomyocytes, où la surexpression de la plakoglobine a conduit à un remplacement fibro-graisseux des cellules cardiaques et à une altération de la signalisation Wnt/β-caténine. Cependant, le rôle de la plakoglobine dans les adipocytes et l’adipogenèse demeure inconnu. Le premier objectif de cette thèse est d'explorer l'hypothèse selon laquelle la plakoglobine joue un rôle régulateur dans l'adipogenèse. Pour tester cette hypothèse, une déplétion ciblée de la plakoglobine par siARN a été réalisée dans des cellules 3T3-L1 et des cellules souches adipeuses d'origine humaine avant d'induire leur différenciation. Il a été démontré que la plakoglobine possède un effet conservé entre espèces, car sa déplétion inhibe l'adipogenèse en réduisant l'expression de PPARγ2 et en altérant l'accumulation lipidique. Des essais TOPFlash ont révélé que la plakoglobine n'affectait pas l'activité transcriptionnelle de Wnt, suggérant l'implication d'un autre mécanisme. Le deuxième objectif était de confirmer les effets de la plakoglobine sur l'expansion des adipocytes in vivo. À cette fin, la plakoglobine a été supprimée dans les adipocytes matures de souris. Cette suppression a entraîné des effets divergents selon le sexe, augmentant le poids corporel total chez les femelles. Chez les mâles, lorsqu'ils ont été soumis à un régime riche en graisses pour évaluer son influence sur l'obésité, les souris mâles ont montré une exacerbation de la résistance à l'insuline. En conclusion, nous avons défini un rôle conservé entre-espèces pour la plakoglobine dans la différenciation des adipocytes in vitro et démontré son effet sur le remodelage adipocytaire in vivo. De plus, elle exacerbe les troubles métaboliques induits par l'obésité de manière dépendante du sexe, suggérant son implication dans le métabolisme systémique. Notre découverte contribue à combler les lacunes dans la compréhension des mécanismes régulateurs de l'expansion adipocytaire et fournit un cadre méthodologique permettant à de futures études d'approfondir cette thématique avec une approche similaire.Obesity is currently a global epidemic, and increasing in prevalence every year. Generally characterized by an imbalance between energy expenditure and energy intake, obesity is associated with multiple comorbidities. Excess energy is stored within adipocytes, inducing adipose tissue remodelling through either hyperplasia or hypertrophy. Our knowledge of the various regulatory mechanisms governing hyperplasia of adipocytes remains incomplete. Previously, our lab defined a role for the scaffold protein 14-3-3ζ in the expansion of visceral adipose tissue and the exacerbation of diet induced obesity. Proteomic analysis revealed the interactome of 14-3-3ζ within adipose tissue, and identified binding partners which are known, as well as unknown, regulators of adipogenesis. One such candidate was plakoglobin, a close homolog of β-catenin. The Wnt/β-catenin axis is known to be inhibitory towards adipogenesis in vitro, biasing progenitor cells towards osteogenic fates. In certain contexts, plakoglobin is capable of inhibiting Wnt/β-catenin transcriptional activity, preferentially activating a different subset of downstream target genes. Evidence of this was found in studies within cardiomyocytes, where overexpression of plakoglobin led to fibrofatty replacement of cardiac cells and impaired Wnt/β-catenin signalling. However, plakoglobin’s role in adipocytes and adipogenesis had yet to be studied. The first aim of this thesis seeks to explore the hypothesis that plakoglobin holds a regulatory function in adipogenesis. To test this hypothesis, siRNA targeted depletion of plakoglobin was performed in 3T3-L1 and human-derived adipose stem cells, before inducing differentiation. Plakoglobin was found to hold a species-conserved effect, as its depletion inhibited adipogenesis, via downregulation of PPARγ2 and impairment of lipid accumulation. TOPFlash assays revealed plakoglobin did not affect Wnt transcriptional activity, suggesting an alternative mechanism may be responsible. The second aim was to confirm plakoglobin’s effects on adipocyte expansion in vivo. To that end, plakoglobin was deleted in mature adipocytes of mice. It exhibited sex-divergent effects, leading to increases in whole-body weight in females, with no changes pbserved in adipogenic genes for either sex. When challenged with a high-fat diet to assess its influence on obesity, male mice displayed an exacerbation of insulin resistance. In conclusion, we have defined a species-conserved role for plakoglobin in adipocyte differentiation in vitro, and shown it to affect whole body weight in and obesity-induced metabolic disturbances in a sex-dependent manner in vivo. Our discovery aids in filling gaps in our knowledge on the regulatory mechanisms governing adipocyte expansion and provides a methodological framework for future studies using a similar approach
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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