71 research outputs found

    Functions of the Nonsense-Mediated mRNA Decay Pathway in Drosophila Development

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    Nonsense-mediated mRNA decay (NMD) is a cellular surveillance mechanism that degrades transcripts containing premature translation termination codons, and it also influences expression of certain wild-type transcripts. Although the biochemical mechanisms of NMD have been studied intensively, its developmental functions and importance are less clear. Here, we describe the isolation and characterization of Drosophila “photoshop” mutations, which increase expression of green fluorescent protein and other transgenes. Mapping and molecular analyses show that photoshop mutations are loss-of-function mutations in the Drosophila homologs of NMD genes Upf1, Upf2, and Smg1. We find that Upf1 and Upf2 are broadly active during development, and they are required for NMD as well as for proper expression of dozens of wild-type genes during development and for larval viability. Genetic mosaic analysis shows that Upf1 and Upf2 are required for growth and/or survival of imaginal cell clones, but this defect can be overcome if surrounding wild-type cells are eliminated. By contrast, we find that the PI3K-related kinase Smg1 potentiates but is not required for NMD or for viability, implying that the Upf1 phosphorylation cycle that is required for mammalian and Caenorhabditis elegans NMD has a more limited role during Drosophila development. Finally, we show that the SV40 3′ UTR, present in many Drosophila transgenes, targets the transgenes for regulation by the NMD pathway. The results establish that the Drosophila NMD pathway is broadly active and essential for development, and one critical function of the pathway is to endow proliferating imaginal cells with a competitive growth advantage that prevents them from being overtaken by other proliferating cells

    DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

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    We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

    Partial shadings on PV arrays: by-pass diode benefits analysis

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    We present a methodology for the analysis and the evaluation of the electrical effects of partial shadings on a PV array. This methodology is namely developed in a pedagogic tool of the software PVsyst, which aims to explain how a shaded cell or group of cells behaves within a PV array. We use this tool for understanding the functions of the by-pass diodes, and quantify the array electrical losses in some typical situations, when one or several cells are shaded. We show that the electrical shading effect is dependent either on the length of the strings, and on the number of strings in parallel. This method should be applied for accurate shading calculations within the simulation process of PVsyst in a near future

    Appréciation de l'état sanitaire d'un effectif de sangliers (Sus scrofa) par l'étude de l'incidence des strongyloses respiratoires

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    Après la réalisation d'un inventaire parasitologique sur des sangliers tués à la chasse, l'auteur cherche une éventuelle relation entre métastrongylose et croissance pour traduire la qualité de l'état sanitaire de ces animaux grâce à différents paramètres : lésions pulmonaires, âge, poids, sexe et biotope. Il s'ensuit une réflexion sur les bonnes pratiques d'agrainage pour minimiser le risque parasitaire sur ces sites.NANTES-Ecole Nat.Vétérinaire (441092302) / SudocSudocFranceF

    Performance assessment of a simulation model for PV modules of any available technology

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    From long-term detailed measurements of several PV modules of all commercialized technologies, this work aims to analyze the results of the “standard” one-diode model, and suggests some modifications for improving it, especially for amorphous, microcrystalline and CdTe modules. We found that for any module an exponential behaviour of the shunt resistance parameter should be taken into account. We identified two other corrections (recombination losses and spectral correction) in order to improve the modelling of amorphous technology modules. These improvements have been implemented in the PVsyst software developed at the University of Geneva

    Gait Complexity and Regularity Are Differently Modulated by Treadmill Walking in Parkinson's Disease and Healthy Population

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    Variability raises considerable interest as a promising and sensitive marker of dysfunction in physiology, in particular in neurosciences. Both internally (e.g., pathology) and/or externally (e.g., environment) generated perturbations and the neuro-mechanical responses to them contribute to the fluctuating dynamics of locomotion. Defective internal gait control in Parkinson's disease (PD), resulting in typical timing gait disorders, is characterized by the breakdown of the temporal organization of stride duration variability. Influence of external cue on gait pattern could be detrimental or advantageous depending on situations (healthy or pathological gait pattern, respectively). As well as being an interesting rehabilitative approach in PD, treadmills are usually implemented in laboratory settings to perform instrumented gait analysis including gait variability assessment. However, possibly acting as an external pacemaker, treadmill could modulate the temporal organization of gait variability of PD patients which could invalidate any gait variability assessment. This study aimed to investigate the immediate influence of treadmill walking (TW) on the temporal organization of stride duration variability in PD and healthy population. Here, we analyzed the gait pattern of 20 PD patients and 15 healthy age-matched subjects walking on overground and on a motorized-treadmill (randomized order) at a self-selected speed. The temporal organization and regularity of time series of walking were assessed on 512 consecutive strides and assessed by the application of non-linear mathematical methods (i.e., the detrended fluctuation analysis and power spectral density; and sample entropy, for the temporal organization and regularity of gait variability, respectively). A more temporally organized and regular gait pattern seems to emerge from TW in PD while no influence was observed on healthy gait pattern. Treadmill could afford the necessary framework to regulate gait rhythmicity in PD. Overall, the results support the hypothesis of a greater dependence to regulatory inputs as an explanatory factor of treadmill influence observed in PD. Also, since treadmill misrepresents the gait as more healthy than it is, the present findings underline that gait analysis using treadmill devices should be cautiously considered in PD and especially for gait variability assessment in gait lab
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