1,720,960 research outputs found
Influence de la méthionine synthase sur la neurogenèse postnatale & conséquences ophtalmologiques de l’invalidation de la méthionine synthase
No full textInborn defects in vitamin B12 (cobalamin) metabolism including CblG pathology caused by mutations in the MTR gene encoding the methionine synthase (MS) enzyme are responsible for the development of persistent symptoms upon treatment, particularly neurological, neurocognitive, and ophthalmological symptoms. However, the mechanisms underlying the development of these symptoms remain largely unknown. The aim of this project is to study in a conditional mouse model of MS deficiency, the consequences of Mtr gene deletion in the brain and retina in order to provide a better understanding of the mechanisms underlying the neurological, neurocognitive, and ocular disorders found in CblG patients. We found that selective invalidation of Mtr in the brain leads to severe metabolic alterations. Our results showed a deregulation of the Wnt/β.catenin signaling pathways that directly involving the GSK3β protein and the SIRT1 protein thus affecting postnatal neurogenesis through the deregulation of the differentiation balance associated with an alteration of neural stem cell and progenitor proliferation. These defects in neurogenesis seem to come with abnormalities in energy metabolism and mitochondrial biogenesis, involving the SIRT1 protein and thus favoring the activation of the intrinsic apoptotic cascade in the hippocampus of MS deficient mice. These neurogenesis abnormalities as well as mitochondrial alterations appear to be two major mechanisms involved in the development of neurological disorders. GSK3β and SIRT1 proteins seem to be two therapeutic targets of interest from the perspective of a treatment aiming to correct the neurological defects in CblG pathologies.In the retina, MS invalidation resulted in major metabolic alterations associated with changes in DNA methylation and a decrease in visual acuity in MS-deficient mice without visible fundus abnormalities. The results of our studies have shown an involvement of retinoid metabolism genes associated with a specific decrease in cone photoreceptor cells, which may contribute to the decrease in visual acuity measured in MS deficient mice. This preliminary work will require further investigation but provides for the first-time evidence of retinal abnormalities in MS deficient mice.Les défauts innés du métabolisme de la vitamine B12 (cobalamine) incluant la pathologie CblG causée par des mutations du gène MTR codant pour l’enzyme méthionine synthase (MS) sont responsables du développement de symptômes persistants aux traitements en particulier des symptômes neurologiques, neurocognitifs et ophtalmologiques. Cependant les mécanismes sous-jacents au développement de ces symptômes restent largement méconnus. L’objectif de ce projet est d’étudier dans un modèle murin conditionnel de déficience en MS, les conséquences de la délétion du gène Mtr dans le cerveau et dans la rétine afin d’apporter une meilleure compréhension des mécanismes à l’origine des troubles neurologiques, neurocognitifs et oculaires retrouvés chez les patients CblG. Nous avons constaté que l'invalidation sélective de Mtr dans le cerveau entraine des altérations métaboliques sévères. Nos résultats ont mis en évidence une dérégulation de la voie de signalisation Wnt/β.caténine impliquant directement la protéine GSK3β et la protéine SIRT1, affectant ainsi la neurogenèse postnatale à travers une dérégulation de la balance de différenciation associée à une altération de la prolifération des cellules souches neurales et progénitrices. Ces défauts de neurogenèse semblent s’accompagner d’anomalies du métabolisme énergétique ainsi que de la biogenèse mitochondriale impliquant la protéine SIRT1 et favorisant ainsi l’activation de la cascade apoptotique intrinsèque dans l’hippocampe des souris déficientes en MS. Ces anomalies de neurogenèse ainsi que les altérations mitochondriales semblent être deux mécanismes majeurs participant au développement des troubles neurologiques. Les protéines GSK3β et SIRT1 semblent être deux cibles thérapeutiques d’intérêts dans l’optique d’un traitement visant à corriger les défauts neurologiques dans la pathologie CblG.Dans la rétine l’invalidation de la MS a entrainé des altérations métaboliques majeures associées à des modifications de la méthylation de l’ADN ainsi qu’à une baisse de l’acuité visuelle chez les souris MS déficientes sans pour autant entrainer d’anomalies visibles du fond d’œil. Les résultats de notre étude ont permis de mettre en évidence une possible implication de gènes du métabolisme des rétinoïdes associée à une baisse spécifique des cellules photoréceptrices de type cône pouvant ainsi participer à la baisse de l’acuité visuelle chez les souris déficientes en MS. Ces travaux préliminaires nécessiteront d’autres investigations, mais apportent cependant pour la première fois l’évidence d’anomalies rétiniennes en condition de déficience en MS
Influence of methionine synthase on postnatal neurogenesis & ophthalmological consequences of invalidation of methionine synthase
No full textLes défauts innés du métabolisme de la vitamine B12 (cobalamine) incluant la pathologie CblG causée par des mutations du gène MTR codant pour l’enzyme méthionine synthase (MS) sont responsables du développement de symptômes persistants aux traitements en particulier des symptômes neurologiques, neurocognitifs et ophtalmologiques. Cependant les mécanismes sous-jacents au développement de ces symptômes restent largement méconnus. L’objectif de ce projet est d’étudier dans un modèle murin conditionnel de déficience en MS, les conséquences de la délétion du gène Mtr dans le cerveau et dans la rétine afin d’apporter une meilleure compréhension des mécanismes à l’origine des troubles neurologiques, neurocognitifs et oculaires retrouvés chez les patients CblG. Nous avons constaté que l'invalidation sélective de Mtr dans le cerveau entraine des altérations métaboliques sévères. Nos résultats ont mis en évidence une dérégulation de la voie de signalisation Wnt/β.caténine impliquant directement la protéine GSK3β et la protéine SIRT1, affectant ainsi la neurogenèse postnatale à travers une dérégulation de la balance de différenciation associée à une altération de la prolifération des cellules souches neurales et progénitrices. Ces défauts de neurogenèse semblent s’accompagner d’anomalies du métabolisme énergétique ainsi que de la biogenèse mitochondriale impliquant la protéine SIRT1 et favorisant ainsi l’activation de la cascade apoptotique intrinsèque dans l’hippocampe des souris déficientes en MS. Ces anomalies de neurogenèse ainsi que les altérations mitochondriales semblent être deux mécanismes majeurs participant au développement des troubles neurologiques. Les protéines GSK3β et SIRT1 semblent être deux cibles thérapeutiques d’intérêts dans l’optique d’un traitement visant à corriger les défauts neurologiques dans la pathologie CblG.Dans la rétine l’invalidation de la MS a entrainé des altérations métaboliques majeures associées à des modifications de la méthylation de l’ADN ainsi qu’à une baisse de l’acuité visuelle chez les souris MS déficientes sans pour autant entrainer d’anomalies visibles du fond d’œil. Les résultats de notre étude ont permis de mettre en évidence une possible implication de gènes du métabolisme des rétinoïdes associée à une baisse spécifique des cellules photoréceptrices de type cône pouvant ainsi participer à la baisse de l’acuité visuelle chez les souris déficientes en MS. Ces travaux préliminaires nécessiteront d’autres investigations, mais apportent cependant pour la première fois l’évidence d’anomalies rétiniennes en condition de déficience en MS.Inborn defects in vitamin B12 (cobalamin) metabolism including CblG pathology caused by mutations in the MTR gene encoding the methionine synthase (MS) enzyme are responsible for the development of persistent symptoms upon treatment, particularly neurological, neurocognitive, and ophthalmological symptoms. However, the mechanisms underlying the development of these symptoms remain largely unknown. The aim of this project is to study in a conditional mouse model of MS deficiency, the consequences of Mtr gene deletion in the brain and retina in order to provide a better understanding of the mechanisms underlying the neurological, neurocognitive, and ocular disorders found in CblG patients. We found that selective invalidation of Mtr in the brain leads to severe metabolic alterations. Our results showed a deregulation of the Wnt/β.catenin signaling pathways that directly involving the GSK3β protein and the SIRT1 protein thus affecting postnatal neurogenesis through the deregulation of the differentiation balance associated with an alteration of neural stem cell and progenitor proliferation. These defects in neurogenesis seem to come with abnormalities in energy metabolism and mitochondrial biogenesis, involving the SIRT1 protein and thus favoring the activation of the intrinsic apoptotic cascade in the hippocampus of MS deficient mice. These neurogenesis abnormalities as well as mitochondrial alterations appear to be two major mechanisms involved in the development of neurological disorders. GSK3β and SIRT1 proteins seem to be two therapeutic targets of interest from the perspective of a treatment aiming to correct the neurological defects in CblG pathologies.In the retina, MS invalidation resulted in major metabolic alterations associated with changes in DNA methylation and a decrease in visual acuity in MS-deficient mice without visible fundus abnormalities. The results of our studies have shown an involvement of retinoid metabolism genes associated with a specific decrease in cone photoreceptor cells, which may contribute to the decrease in visual acuity measured in MS deficient mice. This preliminary work will require further investigation but provides for the first-time evidence of retinal abnormalities in MS deficient mice
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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