48 research outputs found

    GLP, une nouvelle protéine associée au récepteur AT1, induit de l'hypertrophie dans les cellules du tubule proximal du rein du rat

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    Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

    Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells

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    Caveolin-3 is the major structural protein of caveolae in muscle. Mutations in the CAV3 gene cause different types of myopathies with altered membrane integrity and repair, expression of muscle proteins, and regulation of signaling pathways. We show here that myotubes from patients bearing the CAV3P28L and R26Q mutations present a dramatic decrease of caveolae at the plasma membrane, resulting in abnormal response to mechanical stress. Mutant myotubes are unable to buffer the increase in membrane tension induced by mechanical stress. This results in impaired regulation of the IL6/STAT3 signaling pathway leading to its constitutive hyperactivation and increased expression of muscle genes. These defects are fully reversed by reassembling functional caveolae through expression ofcaveolin-3. Our study reveals that under mechanical stress the regulation of mechan-oprotection by caveolae is directly coupled with the regulation of IL6/STAT3 signaling inmuscle cells and that this regulation is absent in Cav3-associated dystrophic patients

    ESKIMO1 Disruption in Arabidopsis Alters Vascular Tissue and Impairs Water Transport

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    Water economy in agricultural practices is an issue that is being addressed through studies aimed at understanding both plant water-use efficiency (WUE), i.e. biomass produced per water consumed, and responses to water shortage. In the model species Arabidopsis thaliana, the ESKIMO1 (ESK1) gene has been described as involved in freezing, cold and salt tolerance as well as in water economy: esk1 mutants have very low evapo-transpiration rates and high water-use efficiency. In order to establish ESK1 function, detailed characterization of esk1 mutants has been carried out. The stress hormone ABA (abscisic acid) was present at high levels in esk1 compared to wild type, nevertheless, the weak water loss of esk1 was independent of stomata closure through ABA biosynthesis, as combining mutant in this pathway with esk1 led to additive phenotypes. Measurement of root hydraulic conductivity suggests that the esk1 vegetative apparatus suffers water deficit due to a defect in water transport. ESK1 promoter-driven reporter gene expression was observed in xylem and fibers, the vascular tissue responsible for the transport of water and mineral nutrients from the soil to the shoots, via the roots. Moreover, in cross sections of hypocotyls, roots and stems, esk1 xylem vessels were collapsed. Finally, using Fourier-Transform Infrared (FTIR) spectroscopy, severe chemical modifications of xylem cell wall composition were highlighted in the esk1 mutants. Taken together our findings show that ESK1 is necessary for the production of functional xylem vessels, through its implication in the laying down of secondary cell wall components

    A Focus on Natural Variation for Abiotic Constraints Response in the Model Species Arabidopsis thaliana

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    Plants are particularly subject to environmental stress, as they cannot move from unfavourable surroundings. As a consequence they have to react in situ. In any case, plants have to sense the stress, then the signal has to be transduced to engage the appropriate response. Stress response is effected by regulating genes, by turning on molecular mechanisms to protect the whole organism and its components and/or to repair damage. Reactions vary depending on the type of stress and its intensity, but some are commonly turned on because some responses to different abiotic stresses are shared. In addition, there are multiple ways for plants to respond to environmental stress, depending on the species and life strategy, but also multiple ways within a species depending on plant variety or ecotype. It is regularly accepted that populations of a single species originating from diverse geographic origins and/or that have been subjected to different selective pressure, have evolved retaining the best alleles for completing their life cycle. Therefore, the study of natural variation in response to abiotic stress, can help unravel key genes and alleles for plants to cope with their unfavourable physical and chemical surroundings. This review is focusing on Arabidopsis thaliana which has been largely adopted by the global scientific community as a model organism. Also, tools and data that facilitate investigation of natural variation and abiotic stress encountered in the wild are set out. Characterization of accessions, QTLs detection and cloning of alleles responsible for variation are presented

    Rare and low-frequency coding variants alter human adult height

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    Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

    Quand la pandémie perdure : les préoccupations sous- jacentes aux gestes professionnels d’enseignant.e.s à l’éducation préscolaire et à l’enseignement primaire

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    À l’hiver 2021, alors que le contexte pandémique prévalait depuis près de deux ans, mais que le contexte d’urgence n’était plus aussi prégnant, treize enseignant.e.s de l’éducation préscolaire et de l’enseignement primaire ont témoigné de l’influence de la pandémie sur leur pratique. L’analyse des transcriptions a révélé que le maintien d’une atmosphère positive et la priorisation des savoirs enseignés étaient au cœur du discours des enseignant.e.s. En ce sens, dans cette période d’incertitude, ces préoccupations semblaient prendre davantage d’importance

    Précipitation de phases hydroxydes doubles lamellaires et piégeage du chromeVI

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    National audienceLa métallurgie et plus spécifiquement le secteur du traitement de surface génèrent de grandes quantités d'effluents industriels à base de métaux lourds, notamment de zinc, de nickel et de chrome VI. Les entreprises de ce secteur sont donc contraintes de traiter leurs effluents industriels afin de répondre à l'arrêté du 26 septembre 1985 leur imposant des règles strictes en matière de rejets dans un réseau d'assainissement urbain ou dans le milieu naturel (Cr VI : 0,1mg/L ; Zn et Ni : 5mg/L). Il a été montré que l'ajout de cations métalliques trivalents Al3+ et Fe3+, lors de la précipitation des ions nickel et zinc, permettait d'obtenir des boues sous forme d'hydroxydes doubles lamellaires (HDL) plus stables que les boues classiques et valorisables. Cette étude a pour but de : - optimiser la précipitation de Zn2+ et Ni2+ sous forme d'HDL grâce à l'ajout d'Al3+ ou de Fe 3+, - étudier la stabilité de ces phases en vue de leur valorisation, - évaluer la capacité des phases HDL synthétisées à piéger le chrome VI sous forme d'ions CrO4 2-. Nous avons synthétisé, à l'échelle du laboratoire, les phases HDL de type Zn-Ni-Al – SO4 et Zn-Ni-Fe – SO4, par co-précipitation à pH constant, en faisant varier les paramètres suivants : pH, rapport MII/MIII et concentration des sels. Les composés obtenus ont ensuite été caractérisés grâce à l'analyse chimique, à la diffraction des rayons X et à la spectroscopie infrarouge, ce qui a permis de confirmer l'existence d'une structure de type HDL. Nous avons étudié la stabilité des phases obtenues HDL ainsi que leur capacité à piéger le chrome VI par adsorption. Elles présentent une grande stabilité lorsqu'elles sont mises en solution à des pH supérieurs à 8,5. En revanche, elles ont tendance à se solubiliser lorsqu'on diminue le pH. Les isothermes d'adsorption de chrome VI ont montré que le taux d'échange et l'affinité adsorbat/adsorbant augmentaient avec le ratio MII/MIII. Ces deux paramètres sont plus importants lorsque l'adsorption des chromates est réalisée sur une phase à base de fer Zn-Ni-Fe – SO4. Cette étude montre que des phases HDL pouvent être obtenues lors de la précipitation d'effluents issus d'ateliers du traitement de surface. Ces phases, stables à pH basique, pouvant adsorber des ions chrome hexavalent, pourrait donc ouvrir la voie à la valorisation des boues d'hydroxydes métalliques

    How and when do expert emergency physicians generate and evaluate diagnostic hypotheses? A qualitative study using head-mounted video cued-recall interviews

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    Study objective: The ability to make a diagnosis is a crucial skill in emergency medicine. Little is known about the way emergency physicians reach a diagnosis. This study aims to identify how and when, during the initial patient examination, emergency physicians generate and evaluate diagnostic hypotheses. Methods: We carried out a qualitative research project based on semistructured interviews with emergency physicians. The interviews concerned management of an emergency situation during routine medical practice. They were associated with viewing the video recording of emergency situations filmed in an "own-point-of-view" perspective. Results: The emergency physicians generated an average of 5 diagnostic hypotheses. Most of these hypotheses were generated before meeting the patient or within the first 5 minutes of the meeting. The hypotheses were then rank ordered within the context of a verification procedure based on identifying key information. These tasks were usually accomplished without conscious effort. No hypothesis was completely confirmed or refuted until the results of investigations were available. Conclusion: The generation and rank ordering of diagnostic hypotheses is based on the activation of cognitive processes, enabling expert emergency physicians to process environmental information and link it to past experiences. The physicians seemed to strive to avoid the risk of error by remaining aware of the possibility of alternative hypotheses as long as they did not have the results of investigations. Understanding the diagnostic process used by emergency physicians provides interesting ideas for training residents in a specialty in which the prevalence of reasoning errors leading to incorrect diagnoses is high
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