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    Study of the contribution of muscle inflammation, IMAT origin and microenvironment to sarcopenic obesity

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    Introduction The optimal condition for skeletal muscle function is represented by an efficient activation of processes that regulate muscle development, growth, regeneration and metabolism. When the balance among these events is missing, a pathological condition arise. In particular, loss or decrease of skeletal muscle function and mass is linked with severe health diseases such as muscle dystrophies, cancer, obesity and aging process. In this context, sarcopenic obesity, a metabolic disorder followed by atrophy of muscle fibres and reduction of stem cell reservoir (satellite cells in muscle) is associated with increasing ectopic adipose tissue, impairing glucose tolerance and decreasing strength and mobility in old adults. This excess of fatty acids accumulated in several other organs, including skeletal muscle, induces metabolic dysfunctions, β-oxidative alterations, increase of ROS production, lipotoxicity and insulin resistance. Moreover this intermuscular adipose tissue (IMAT) acts as chemoattractant for inflammatory cells, chiefly macrophages, which produce high amount of pro-inflammatory cytokines (TNF-α, IL-6, IL-1, INFγ) and low of anti-inflammatory cytokines (IL-4, IL-10) resulting in chronic low-grade systemic inflammation and muscle loss. Aims The aim of this work is to investigate the origin of intermuscular fat and the complex mechanisms regulating the crosstalk with the surrounding muscle. In the first part of the study we try to understand the differences in muscle inflammation in obese subjects both normoglycemic and diabetic versus healthy patients using muscle biopsies. Moreover, in the same groups of patients, we attempt to identify serum microRNAs as possible useful markers of muscle alterations in presence of obesity. Because it is well known that in chronic diseases, as obesity and diabetes, multifactorial components contribute to the pathology, we decided to investigate the microenvironment of skeletal muscle, represented by extracellular matrix (ECM). We aim to understand if it could have had a role in the deposition of IMAT and on associated inflammatory processes using an obese mouse model. Material and methods From healthy and obese patients either normoglycemic or diabetic, both muscle biopsies and serum samples were collected. By Real-time PCR the first were analysed for selected inflammation markers, whereas the second for the principal muscle circulating miRNAs. In the second part of the study, a detergent-enzymatic decellularization protocol for wild type (C57BL6J) and ob/ob (B6.Cg-Lepob/J) murine quadriceps were set and samples were characterized for DNA content and ECM structure preservation. After that, a volumetric muscle loss model on wild-type mice was created and ECMs from wt or ob/ob quadriceps mice were implanted. The ability of the matrices to be remodelled and reabsorbed was evaluated by immunofluorescence and molecular analysis after 7, 15 and 30 days. Results and discussion mRNA from three human rectus abdomins biopsies from obese patients both normoglycemic and diabetic and three peroneal muscle biopsies from healthy subjects indicate an increase in pro-inflammatory gene expression both in normoglycemic and diabetic patients in comparison with the controls. However, in contrast to what we expected, diabetic subjects, that were under Metformin treatment from at least 1 year, showed a reduction of inflammation. The serum miR133a, miR133b and miR1 levels of healthy and obese patients both normoglycemic and diabetic, display the same trend previously described for muscle biopsies. This suggests a possible direct correlation between muscle inflammation and the release of these circulating miRNAs, which could be used in the future as indicative markers of patient muscle alterations. On the other hand, the decellularization of wild type (wt) and ob/ob quadriceps did not show significant structural differences between the two samples. In vivo transplantation of the two decellularized muscle matrix (ECMs) in wt injured mice induced after 7 days a strong cells migration in the interface between the native tissue and the matrix that gradually diminished after 15 and 30 days. . Pan macrophages cells (CD68+ cells) were found in both ECM implantation, mainly in the area around the stitches and in the interface between the matrix and the native tissue, but in the inner part of the recipient absence of inflammatory infiltrate was evident at all time points. Alcian blue and Masson’s Trichrome stains highlighted similar GAG deposition and collagen components between wt and ob/ob donor ECM. In particular we observed that the scaffold derived from donor affected by a metabolic disease did no induce alteration in structural matrix deposition but promoted a premature M2 inflammation that was reduced or stabilised after 30 days. On the contrary healthy ECM in wt mice start later the tissue rebuilding leading to a more complete regeneration. No differences were also observed in activation or modulation of myogenic and adipogenic pathways after both implantations

    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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