1,721,063 research outputs found
Evaluation of the therapeutic potential of inhibitors of the phosphatase complex PP1c/GADD34 on the integrated stress response during extracorporeal circulation
No full textLa circulation extracorporelle (CEC) est une procédure gold standard en chirurgie cardiaque permettant la suppléance de la fonction cardio-pulmonaire. Le contact entre le sang et les surfaces du circuit initie une inflammation à l’origine d’un syndrome de réponse inflammatoire systémique et dérégulation de l’homéostasie. Les conséquences associées peuvent entraîner une dysfonction multi-organe chez les patients. Dans ce contexte, il devient urgent de développer de nouveaux moyens pharmacologiques permettant de réduire les conséquences d’une CEC. La modulation de de la voie de réponse au stress (ISR), voie de réponse au stress ubiquitaire serait une approche prometteuse ayant déjà fait ses preuves dans d’autres pathologies. L’activation de l’ISR permet la mise en place d’une réponse cellulaire orientée vers la résolution des stress. L’objectif de ma thèse a été d’évaluer le potentiel effet thérapeutiques de petites molécules inhibitrice du complexe de phosphatase GADD34/PP1c, responsable de la terminaison de l’ISR. Pour cela un modèle de rat mimant une CEC et ses conséquences a été mis au point. La pertinence de ce modèle a été d’abord validé pour un usage préclinique par un monitorage hémodynamique et biochimique et par comparaison des paramètres biochimique avec ceux trouvés chez l’Homme. Enfin, nous avons mis en évidence des effets bénéfiques hémodynamiques, pulmonaires, rénaux, cérébraux après l’administration des molécules, associés à un effet anti-inflammatoire sur ce modèle. Ces effets et les mécanismes associés sont en cours de caractérisation.Cardiopulmonary bypass (CPB) is a gold standard procedure in cardiac surgery that aim to replace cardio-pulmonary function. The blood contact with the extrinsic elements of the circuit promotes inflammation leading to a systemic inflammatory response syndrome and homeostasis dysregulation. The consequences of this deregulation can lead to multi-organ dysfunction. In this context, there is an urgent need to develop new pharmacological approach to reduce the consequences of CPB. Modulation of the ubiquitous stress response pathway (ISR) is a promising approach that has already been proven in other pathologies. ISR activation allows an adapted cellular response for the resolution of stress. The aim of my thesis was to evaluate the therapeutic effect of inhibitors of the GADD34/PP1c phosphatase complex responsible for the termination of ISR. To this purpose, a rat model mimicking CPB was developed. The relevance of this model was first validated for preclinical use by hemodynamic and biochemical monitoring and by comparison to parameters found in humans. Finally, we have demonstrated beneficial effects on hemodynamic, pulmonary, renal, and cerebral parameters after administration of the compounds, associated with an antiinflammatory effect on this model. These effects and the associated mechanisms are currently being under investigation
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
Interest of O-GlcNAcylation stimulation in the early management of hemorrhagic and septic shock
No full textL'état de choc se définit comme une insuffisance circulatoire aigue aboutissant à une hypoxie tissulaire. Les chocs septique et hémorragique sont les deux types de choc les plus fréquents et sont responsables respectivement de 11 et 1,9 million de décès chaque année dans le monde. Du fait de l'usage de traitements symptomatiques face à ces pathologies complexes, la mortalité des états de choc reste élevée. La O-GlcNAcylation est une modification post-traductionnelle émergente notamment impliquée dans la réponse au stress et la survie cellulaire. Les objectifs de ma thèse ont été d'étudier si une stimulation de la O-GlcNAcylation est bénéfique dans la prise en charge précoce des chocs septique et hémorragique, mais également d'identifier les mécanismes associés. Pour cela, des modèles de rat en choc septique ou hémorragique ont été mis au point et traités ou non avec du NButGT, molécule permettant de stimuler les niveaux de O-GlcNAcylation. Nous avons pu démontrer que le traitement au NButGT augmente les niveaux de O-GlcNAcylation et que cette augmentation est associée à une amélioration de l'état de santé des animaux et ceux dans les deux modèles. Une approche de O-GlcNAcylomique nous a permis d'identifier des protéines O-GlcNAcylées d'intérêt. En conclusion, la O-GlcNAcylation semble être une piste thérapeutique intéressante dans les états de choc septique et hémorragique. L'identification des mécanismes bénéfiques associés à la stimulation de la O-GlcNAcylation est une perspective majeure.Shock is defined as an acute circulatory failure leading to tissue hypoxia. Septic and hemorrhagic shock are the two most common types of shock and are responsible for 11 and 1.9 million deaths respectively each year worldwide. Due to the use of symptomatic treatments for these complex pathologies, the mortality of shock states remains high. O-GlcNAcylation is an emerging posttranslational modification notably involved in stress response and cell survival. The aims of my thesis were to study whether the stimulation of O-GlcNAcylation is beneficial in the early management of septic and hemorrhagic shock and to identify the associated mechanisms. For this purpose, rat models in septic or hemorrhagic shock were developed and treated or not with NButGT, a molecule which stimulate O-GlcNAcylation levels. We were able to demonstrate that treatment with NButGT increases O-GlcNAcylation levels and that this increase is associated with an improvement in the health status of the animals in both models. An O-GlcNAcylomic approach allowed us to identify O-GlcNAcylated proteins of interest. ln conclusion, O-GlcNAcylation appears to be an interesting therapeutic approach in septic and hemorrhagic shock. The identification of beneficial mechanisms associated with the stimulation of O-GlcNAcylation is a major perspective
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
Roles of 0-GIcNAcylation in development and stress response : new perspectives in pediatrics
No full textLa 0-GIcNAcylation est une modification post-traductionnelle liée au métabolisme et impliquée dans la réponse au stress et la survie cellulaire. La stimulation aiguë de la 0-GIcNAcylation est bénéfique dans différentes situations de réponses inflammatoires chez le rat adulte. Les jeunes, rarement étudiés, sont davantage concernés par ces situations or la physiopathologie et le métabolisme évoluent au cours du développement ce qui pourrait impacter la réponse au traitement. Dans un premier temps, j'ai étudié l'impact de l'âge sur les niveaux de 0-GIcNAcylation et l'expression des enzymes clés dans différents organes à différents âges chez le rat. Les résultats obtenus démontrent que les niveaux de 0-GIcNAcylation sont plus élevés chez le jeune rat. Afin d'évaluer l'impact de ces différences sur la réponse au stress dans plusieurs situations de décompensation cardiaque associées à une réponse inflammatoire, j'ai étudié l'impact de l'augmentation des niveaux de 0-GIcNAcylation dans un modèle de choc septique chez le jeune rat (juste après sevrage). J'ai également mis en place des biocollections de sang et de tissus cardiaques Humains chez des enfants sains, en choc septique et au cours de la circulation extracorporelle CEC. Nous avons démontré que le NButGT est associé à une amélioration des dysfonctions d'organes et une augmentation de la survie. Une approche de 0- GIcNAcylomique nous a permis d'identifier des protéines 0-GIcNAcylées d'intérêt dont l'ATP citrate lyase et l'anhydrase carbonique. L'étude de cette modification post-traductionnelle à la période péri-natale et l'identification des mécanismes bénéfiques associés à la stimulation de la 0-GIcNAcylation constituent des avancées majeures.0-GIcNAcylation is a post-translational modification linked to metabolism and involved in the stress response and cell survival. Acute stimulation of O-GIcNAcylation is beneficial in various inflammatory response situations in adult rats. The young, who are rarely studied, are more concerned by these situations, and pathophysiology and metabolism evolve during development, which could have an impact on the response to treatment. Firstly, I studied the impact of age on 0-GIcNAcylation levels and the expression of key enzymes in different organs at different ages in rats. The results show that 0-GIcNAcylation levels are higher in young rats. In order to assess the impact of these differences on the stress response in several situations of cardiac failure associated inflammatory response, I studied the effect of increased 0-GIcNAcylation levels in a young rat model of septic shock (just after weaning). I also set up biocollections of human blood and cardiac tissue in healthy children, in septic shock and during extracorporeal circulation. We have shown that NButGT is associated with an improvement in organ dysfunction and an increase in survival. An 0-GIcNAcylomics approach in various situations has enabled us to identify 0-GIcNAcylated proteins of interest, including ATP citrate lyase and carbonic anhydrase. The study of this post-translational modification in the peri-natal period and the identification of beneficial mechanisms associated with the stimulation of 0-GIcNAcylation constitute major advances
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
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