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Evidence of gut microbiota - skeletal muscle axis, study with remarquable muscular phenotypes
No full textLe microbiote intestinal est composé de 1014 bactéries essentielles dans la santé de l’individu. Son altération, appelée dysbiose, impacte différents organes (intestin, foie, tissu adipeux) induisant de nombreuses maladies notamment métaboliques. Le muscle squelettique, tissu hautement métabolique et responsable de notre autonomie physique, semble également être sous son influence. Ce doctorat s’est inscrit dans cette problématique émergente de l’existence possible d’un axe microbiote intestinal – muscle squelettique, et d’en comprendre les mécanismes de relation. Nos résultats montrent que les bactéries intestinales sont essentielles à la fonction musculaire squelettique. En effet, la déplétion du microbiote réduit les capacités contractiles musculaires ex-vivo ainsi que le contenu en glycogène musculaire alors que le réensemencement naturel normalise l’ensemble de ces effets. Comprendre la relation fonctionnelle entre microbiote et muscle exige également son étude dans des modèles de phénotypes musculaires remarquables afin d’en révéler l’étendue et se rapprocher de la réalité physiopathologique. Nous avons donc étudié la composition du microbiote intestinal, la fonction et la structure de l’intestin et les liens mécanistiques avec le muscle squelettique chez la souris hypertrophique déficiente en myostatine (KO-mstn), la souris dystrophique mdx, et chez l’Homme avec un modèle original de sédentarité accélérée « Dry Immersion », en collaboration avec le Centre National d’Etudes Spatiales. Nos analyses métagénomiques révèlent des signatures microbiennes spécifiques à chacun des phénotypes musculaires étudiés. Elles suggèrent que la chronicité de l’atteinte musculaire est un facteur dans l’importance des modifications observées au niveau de la flore intestinale. Les marqueurs de diversité sont ainsi fortement altérés dans le phénotype dystrophique mdx, avec une modification plus vaste de la composition bactérienne, un phylum spécifique : Deferribacteres, et des modifications jusqu’au genre pour les phyla Actinobacteria et Proteobacteria. La famille Muribaculaceae est, de façon intéressante, inversement affectée dans nos modèles divergents hypertrophique (KO-mstn) et dystrophique (mdx). De plus, les OTUs relatifs à la famille bactérienne Lachnospiraceae sont impactés dans les trois modèles. La Dry-Immersion de 5 jours modifie les ordres clostridialeso, Lactobacillaceaeo et Selenomonadaleso du phylum Firmicutesp. Ces données suggèrent une implication de certaines familles bactériennes dans le phénotype musculaire. Ces microbiotes intestinaux s’associent parfois à des modifications de fonction et de structure de l’intestin, seule réelle barrière avec le muscle squelettique, ainsi qu’à une moindre production d’acides gras à chaine courte et une surexpression de Fiaf et de marqueurs inflammatoires, potentiellement en lien avec les phénotypes musculaires. En conclusion, ces travaux de thèse apportent un nouvel éclairage sur l’axe microbiote intestinal – muscle squelettique que l’on peut redéfinir en dialogue, avec des pistes de mécanismes sous-jacents. Ils permettent d’envisager l’utilisation du microbiote intestinal comme vecteur d’amélioration de la fonctionnalité́ du muscle squelettique ouvrant ainsi des perspectives thérapeutiques et d’accompagnement pour les nombreuses pathologies affectant le tissu musculaire mais également pour le secteur de la performance sportive.The gut microbiota represents a community of 1,014 bacteria that are essential for the host’ health. Its alteration, called dysbiosis, impacts various organs (intestine, liver, adipose tissue) leading to numerous diseases, in particular metabolic diseases. Skeletal muscle, a highly metabolic tissue responsible for our physical autonomy, also seems to be under its influence. This work is part of the emerging issue on the potential microbiota - skeletal muscle axis, and the understanding of its related mechanisms. Our results show that gut bacteria are essential for skeletal muscle function. In fact, depletion of the microbiota reduces ex-vivo muscle contractile capacities as well as muscle glycogen content, while natural reseeding normalizes all of these deleterious effects. Understanding the functional relationship between these two organs also requires to analyze it in remarkable muscle phenotypes in order to reveal the nature and the extent of the relation and to come closer to the pathophysiological reality. We therefore studied the composition of the gut microbiota, the function and structure of the gut and the mechanistic links with skeletal muscle in myostatin-deficient hypertrophic mice (KO-mstn), dystrophic mdx mice, and in humans with an original model of accelerated hypoactivity “Dry Immersion”, in collaboration with the Centre National d'Etudes Spatiales.Our metagenomic analyses reveal microbial signatures specific to each of the muscle phenotypes studied. It suggested that the chronicity of muscle damage is a factor in the importance of the composition changes observed in the gut microbiota. Diversity markers are thus strongly altered in the dystrophic mdx phenotype, with a more profound modification of the bacterial composition, with specific phylum presence : Deferribacteres; and modifications down to the genus for the Actinobacteria and Proteobacteria phyla. Interestingly, Muribaculaceae family is inversely affected in our opposite phenotypes : hypoetrophic (KO-mstn) and dystrophic (mdx). Moreover, in all three models, OTUs related to the Lachnospiraceae family are impacted suggesting an involvement in the muscle phenotype.After 5-days of Dry Immersion the Clostridiales, Lactobacillaceae and Selenomonadales orders of phylum Firmicutes are modified. These differential gut microbiotas are sometimes associated with changes in the function and structure of the intestine, the only real barrier with skeletal muscle, as well as with a reduce production of short-chain fatty acids and overexpression of Fiaf and inflammatory markers, potentially related to muscle phenotypes. In conclusion, this thesis shed new light on the gut microbiota – skeletal muscle axis, which can be redefined as a reciprocal cross-talk, with clues to the underlying mechanisms. To envisage the use of the gut microbiota as a vector for improving skeletal muscle function is thus possible opening up therapeutic perspectives for the numerous pathologies affecting the muscle tissue but also for the fields of sports performance
Mise en évidence de l’axe microbiote intestinal – muscle squelettique par l’étude de phénotypes musculaires remarquables
No full textThe gut microbiota represents a community of 1,014 bacteria that are essential for the host’ health. Its alteration, called dysbiosis, impacts various organs (intestine, liver, adipose tissue) leading to numerous diseases, in particular metabolic diseases. Skeletal muscle, a highly metabolic tissue responsible for our physical autonomy, also seems to be under its influence. This work is part of the emerging issue on the potential microbiota - skeletal muscle axis, and the understanding of its related mechanisms. Our results show that gut bacteria are essential for skeletal muscle function. In fact, depletion of the microbiota reduces ex-vivo muscle contractile capacities as well as muscle glycogen content, while natural reseeding normalizes all of these deleterious effects. Understanding the functional relationship between these two organs also requires to analyze it in remarkable muscle phenotypes in order to reveal the nature and the extent of the relation and to come closer to the pathophysiological reality. We therefore studied the composition of the gut microbiota, the function and structure of the gut and the mechanistic links with skeletal muscle in myostatin-deficient hypertrophic mice (KO-mstn), dystrophic mdx mice, and in humans with an original model of accelerated hypoactivity “Dry Immersion”, in collaboration with the Centre National d'Etudes Spatiales.Our metagenomic analyses reveal microbial signatures specific to each of the muscle phenotypes studied. It suggested that the chronicity of muscle damage is a factor in the importance of the composition changes observed in the gut microbiota. Diversity markers are thus strongly altered in the dystrophic mdx phenotype, with a more profound modification of the bacterial composition, with specific phylum presence : Deferribacteres; and modifications down to the genus for the Actinobacteria and Proteobacteria phyla. Interestingly, Muribaculaceae family is inversely affected in our opposite phenotypes : hypoetrophic (KO-mstn) and dystrophic (mdx). Moreover, in all three models, OTUs related to the Lachnospiraceae family are impacted suggesting an involvement in the muscle phenotype.After 5-days of Dry Immersion the Clostridiales, Lactobacillaceae and Selenomonadales orders of phylum Firmicutes are modified. These differential gut microbiotas are sometimes associated with changes in the function and structure of the intestine, the only real barrier with skeletal muscle, as well as with a reduce production of short-chain fatty acids and overexpression of Fiaf and inflammatory markers, potentially related to muscle phenotypes. In conclusion, this thesis shed new light on the gut microbiota – skeletal muscle axis, which can be redefined as a reciprocal cross-talk, with clues to the underlying mechanisms. To envisage the use of the gut microbiota as a vector for improving skeletal muscle function is thus possible opening up therapeutic perspectives for the numerous pathologies affecting the muscle tissue but also for the fields of sports performance.Le microbiote intestinal est composé de 1014 bactéries essentielles dans la santé de l’individu. Son altération, appelée dysbiose, impacte différents organes (intestin, foie, tissu adipeux) induisant de nombreuses maladies notamment métaboliques. Le muscle squelettique, tissu hautement métabolique et responsable de notre autonomie physique, semble également être sous son influence. Ce doctorat s’est inscrit dans cette problématique émergente de l’existence possible d’un axe microbiote intestinal – muscle squelettique, et d’en comprendre les mécanismes de relation. Nos résultats montrent que les bactéries intestinales sont essentielles à la fonction musculaire squelettique. En effet, la déplétion du microbiote réduit les capacités contractiles musculaires ex-vivo ainsi que le contenu en glycogène musculaire alors que le réensemencement naturel normalise l’ensemble de ces effets. Comprendre la relation fonctionnelle entre microbiote et muscle exige également son étude dans des modèles de phénotypes musculaires remarquables afin d’en révéler l’étendue et se rapprocher de la réalité physiopathologique. Nous avons donc étudié la composition du microbiote intestinal, la fonction et la structure de l’intestin et les liens mécanistiques avec le muscle squelettique chez la souris hypertrophique déficiente en myostatine (KO-mstn), la souris dystrophique mdx, et chez l’Homme avec un modèle original de sédentarité accélérée « Dry Immersion », en collaboration avec le Centre National d’Etudes Spatiales. Nos analyses métagénomiques révèlent des signatures microbiennes spécifiques à chacun des phénotypes musculaires étudiés. Elles suggèrent que la chronicité de l’atteinte musculaire est un facteur dans l’importance des modifications observées au niveau de la flore intestinale. Les marqueurs de diversité sont ainsi fortement altérés dans le phénotype dystrophique mdx, avec une modification plus vaste de la composition bactérienne, un phylum spécifique : Deferribacteres, et des modifications jusqu’au genre pour les phyla Actinobacteria et Proteobacteria. La famille Muribaculaceae est, de façon intéressante, inversement affectée dans nos modèles divergents hypertrophique (KO-mstn) et dystrophique (mdx). De plus, les OTUs relatifs à la famille bactérienne Lachnospiraceae sont impactés dans les trois modèles. La Dry-Immersion de 5 jours modifie les ordres clostridialeso, Lactobacillaceaeo et Selenomonadaleso du phylum Firmicutesp. Ces données suggèrent une implication de certaines familles bactériennes dans le phénotype musculaire. Ces microbiotes intestinaux s’associent parfois à des modifications de fonction et de structure de l’intestin, seule réelle barrière avec le muscle squelettique, ainsi qu’à une moindre production d’acides gras à chaine courte et une surexpression de Fiaf et de marqueurs inflammatoires, potentiellement en lien avec les phénotypes musculaires. En conclusion, ces travaux de thèse apportent un nouvel éclairage sur l’axe microbiote intestinal – muscle squelettique que l’on peut redéfinir en dialogue, avec des pistes de mécanismes sous-jacents. Ils permettent d’envisager l’utilisation du microbiote intestinal comme vecteur d’amélioration de la fonctionnalité́ du muscle squelettique ouvrant ainsi des perspectives thérapeutiques et d’accompagnement pour les nombreuses pathologies affectant le tissu musculaire mais également pour le secteur de la performance sportive
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
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