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Pathogenetic mechanisms in animal models of Duchenne Muscular Dystrophy
No full textDuchenne muscular dystrophy is the most frequent inherited neuromuscular disease. Its incidence is high: around 1 affected boy out 3500 male births. Genetic counselling is inefficient in case of new mutations which account for 1/3 of the cases. The disease progress so that the DMD boys are wheelchair bound in their first decade and they die in their twenties. No curative therapy is available yet. The defective gene in DMD and its encoded protein, dystrophin, have been known for more than fifteen years, but the mechanisms leading from the absence of dystrophin to the muscle cell death is still poorly understood. Dystrophin binds to the cytoskeleton via subsarcolemmal F-actin and to the extracellular matrix via dystroglycans and laminin; besides, this scaffolding is stabilized by a complex of transmembranous proteins, the function of which remains uncertain.Animals sharing similar genetic defects affecting dystrophin were discovered. CXMD dogs are the most affected, but the mdx mice are definitely the most studied model. The latter show indisputable signs of muscle dystrophy, although they look little affected in vivo despite an absence of dystrophin. The different severity of the disease between the species is a puzzling observation. To better understand the role of dystrophin, an inventory of the defects related to its absence in mdx mice is necessary. In vivo, they show altered force and endurance as well as an raised serum creatine kinase level, as observed in human DMD boys. The improper muscular function is better characterized on isolated muscles. Muscles lacking dystrophin develop less tension. The hallmark of dystrophinopathy is the inability of the affected muscle to sustain the high mechanical stress produced during "eccentric" contractions (in which the muscle is forcibly lengthened while in full contracted state). Contractions following a series of such eccentric contractions show a marked reduction of force. This is correlated with the intracellular accumulation of vital dye, normally excluded from the fibres, witnessing membrane damages. Therefore, an important role of dystrophin is thought to be related to the maintenance of the mechanical integrity of the membrane during the high strains that occur in muscle contractions. In mdx muscle, calcium accumulates with age, as in muscles from DMD boys. The precise localisation of the accumulation is unresolved. [...]La dystrophie musculaire de Duchenne est la myopathie héréditaire la plus fréquente. Elle affecte un enfant toutes les 3500 naissances mâles ; le conseil génétique en est difficile. La perte de la marche survient vers 10 ans et les patients dépassent exceptionnellement 30 ans. Cette maladie est actuellement incurable. Bien que la protéine (la dystrophine) qui fait défaut et son gène soient connus depuis quinze ans, le rôle de cette protéine et la cascade d'évènements s'achevant par la mort de la fibre musculaire restent mystérieux. La dystrophine est une longue protéine située sous le sarcolemme, qui entretient des rapports étroits avec d'autres protéines du cytosquelette ou transmembranaires. Sa fonction est inconnue, mais des rôles de stabilisation membranaire ou dans la transduction du signal sont proposés.
Plusieurs modèles animaux de dystrophie musculaire existent. Le chien dystrophique semble plus affecté, à première vue, que la souris mdx. Cependant cette dernière présente des signes indubitables de dystrophie musculaire. Elle constitue d'ailleurs un modèle largement utilisé. La souris mdx présente une élévation plasmatique de certaines enzymes musculaires. Elle développe une tension diminuée et, surtout, ses muscles sont particulièrement sensibles aux contractions avec étirement forcé (" excentriques "). Après quelques contractions de ce type, le muscle des souris mdx a perdu une grande partie de sa force. Ceci est corrélé avec l'accumulation intracellulaire d'un colorant vital, normalement exclu de la fibre. Ceci suggère que la dystrophine joue un rôle dans le maintien de l'intégrité membranaire. Par ailleurs, il a été démontré qu'avec l'âge, le calcium s'accumule dans le muscle de la souris mdx, sa localisation précise restant incertaine.
En collaboration avec deux laboratoires européens, nous avons modifié le modèle mdx vers l'aggravation ou vers l'amélioration en utilisant des techniques de transgenèse. Leur évaluation fit appel à une batterie de tests fonctionnels.
(1) Le premier modèle a été obtenu en croisant des souris mdx avec des souris déficientes en parvalbumine, un tampon calcique cytosolique. Cette protéine est surexprimée dans le muscle mdx mais n'est présente qu'à l'état de traces dans le muscle humain. Elle pourrait jouer un rôle protecteur en complexant le calcium lors d'influx trop importants. Les signes de dégénérescence et de pseudohypertrophie sont plus marqués dans les muscles du double mutant. Cependant, d'excellentes capacités de régénération permettent à ce modèle murin, dépourvu de parvalbumine et de dystrophine d'être, en apparence, peu différent du modèle mdx. L'absence de parvalbumine peut donc partiellement expliquer le phénotype plus marqué présenté par le patient atteint de DMD, mais cet effet est modeste.
(2) Des souris ont été crées à Oxford. Sur un fond mdx, elles expriment de façon conditionnelle de l'utrophine. Cette protéine est fort semblable à la dystrophine et il existe des preuves qu'elle en possède les capacités fonctionnelles. Cependant, il importait de savoir si une expression importante débutant après la naissance ou le sevrage permettait également une récupération fonctionnelle chez la souris ...(SBIM 3)--UCL, 200
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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