From a movement-deficient grapevine fanleaf virus to the identification of a new viral determinant of nematode transmission

Grapevine fanleaf virus (GFLV) and arabis mosaic virus (ArMV) are nepoviruses responsible for grapevine degeneration. They are specifically transmitted from grapevine to grapevine by two distinct ectoparasitic dagger nematodes of the genus Xiphinema. GFLV and ArMV move from cell to cell as virions through tubules formed into plasmodesmata by the self-assembly of the viral movement protein. Five surface-exposed regions in the coat protein called R1 to R5, which differ between the two viruses, were previously defined and exchanged to test their involvement in virus transmission, leading to the identification of region R2 as a transmission determinant. Region R4 (amino acids 258 to 264) could not be tested in transmission due to its requirement for plant systemic infection. Here, we present a fine-tuning mutagenesis of the GFLV coat protein in and around region R4 that restored the virus movement and allowed its evaluation in transmission. We show that residues T258, M260, D261, and R301 play a crucial role in virus transmission, thus representing a new viral determinant of nematode transmission

Rackham: An Interactive Robot-Guide

International audienceRackham is an interactive robot-guide that has been used in several places and exhibitions. This paper presents its design and reports on results that have been obtained after its deployment in a permanent exhibition. The project is conducted so as to incrementally enhance the robot functional and decisional capabilities based on the observation of the interaction between the public and the robot. Besides robustness and efficiency in the robot navigation abilities in a dynamic environment, our focus was to develop and test a methodology to integrate human-robot interaction abilities in a systematic way. We first present the robot and some of its key design issues. Then, we discuss a number of lessons that we have drawn from its use in interaction with the public and how that will serve to refine our design choices and to enhance robot efficiency and acceptability

Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity.

Some species responded successfully to prehistoric changes in climate [1, 2], while others failed to adapt and became extinct [3]. The factors that determine successful climate adaptation remain poorly understood. We constructed a reference genome and studied physiological adaptations in the Alpine marmot (Marmota marmota), a large ground-dwelling squirrel exquisitely adapted to the "ice-age" climate of the Pleistocene steppe [4, 5]. Since the disappearance of this habitat, the rodent persists in large numbers in the high-altitude Alpine meadow [6, 7]. Genome and metabolome showed evidence of adaptation consistent with cold climate, affecting white adipose tissue. Conversely, however, we found that the Alpine marmot has levels of genetic variation that are among the lowest for mammals, such that deleterious mutations are less effectively purged. Our data rule out typical explanations for low diversity, such as high levels of consanguineous mating, or a very recent bottleneck. Instead, ancient demographic reconstruction revealed that genetic diversity was lost during the climate shifts of the Pleistocene and has not recovered, despite the current high population size. We attribute this slow recovery to the marmot's adaptive life history. The case of the Alpine marmot reveals a complicated relationship between climatic changes, genetic diversity, and conservation status. It shows that species of extremely low genetic diversity can be very successful and persist over thousands of years, but also that climate-adapted life history can trap a species in a persistent state of low genetic diversity.This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001134), the UK Medical Research Council (FC001134), and the Wellcome Trust (FC001134). CB and AC are supported by the Agence Nationale de la Recherche (project ANR-13-JSV7-0005) and the Centre National de la Recherche Scientifique (CNRS), CB is supported by the Rhône-Alpes region (Grant 15.005146.01). LD is supported by Agence Nationale de la Recherche (project ANR-12-ADAP-0009). TIG is supported by a Leverhulme Early Career Fellowship (Grant ECF-2015-453) and a NERC grant (NE/N013832/1). JMG is supported by a Hertha Finberg Fellowship (FWF T703). LDR is supported by the Diabetes UK RD Lawrence Fellowship (16/0005382)

Structural Insights into Viral Determinants of Nematode Mediated Grapevine fanleaf virus Transmission

Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV), a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP), carries the determinants of this specificity. Here, we provide novel insight into GFLV transmission by nematodes through a comparative structural and functional analysis of two GFLV variants. We isolated a mutant GFLV strain (GFLV-TD) poorly transmissible by nematodes, and showed that the transmission defect is due to a glycine to aspartate mutation at position 297 (Gly297Asp) in the CP. We next determined the crystal structures of the wild-type GFLV strain F13 at 3.0 Å and of GFLV-TD at 2.7 Å resolution. The Gly297Asp mutation mapped to an exposed loop at the outer surface of the capsid and did not affect the conformation of the assembled capsid, nor of individual CP molecules. The loop is part of a positively charged pocket that includes a previously identified determinant of transmission. We propose that this pocket is a ligand-binding site with essential function in GFLV transmission by X. index. Our data suggest that perturbation of the electrostatic landscape of this pocket affects the interaction of the virion with specific receptors of the nematode's feeding apparatus, and thereby severely diminishes its transmission efficiency. These data provide a first structural insight into the interactions between a plant virus and a nematode vector

Multiple Changes in Peptide and Lipid Expression Associated with Regeneration in the Nervous System of the Medicinal Leech

peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Esthétique de l'écart dans l'œuvre poétique de Robert Frost

Du recueil A Boy s Will (1913) au recueil In the Clearing (1962), l œuvre du poète américain Robert Frost (1874-1963) déploie sa réflexion sur le concept d écart, et le présente comme principe majeur de son esthétique et de sa stratégie d écriture. Utilisant une approche fondée sur la micro-lecture des poèmes, cette thèse entend mettre en lumière la richesse d'une thématique frostienne qui permet de repenser la dialectique entre centre et marge à différents niveaux d'analyse : cette dialectique semble à l œuvre non seulement dans la représentation poétique des espaces nord-américains mais aussi dans le rapport des textes à l'espace métaphorique du canon, ainsi que dans l'ambiguë mise en scène du sujet dans son rapport aux espaces intime, social et politique. Nous souhaitons montrer que le poète et les personae multiples qu il adopte au fil des recueils privilégient un positionnement détaché, qui n est ni complètement au centre ni complètement à l écart, mais pour ainsi dire dans l écart. Cette position de léger retrait, à la fois sereine et équilibriste, dessine ainsi un triple autoportrait du poète. Il fait le portrait d un artiste chez qui la tension entre tradition et modernité, entre formes fixes et libre expérimentation, relève d'une position compliquée et féconde, qui permet à Frost de se situer à la fois à l'intérieur et légèrement à l'écart du genre de la poésie pastorale ; d'autre part, il esquisse le portrait bougé d'un sujet en mouvement au sein du paysage de Nouvelle-Angleterre, sujet que des tentatives d ancrage dans certains territoires installent dans une position de voisinage méfiant avec son prochain, à la fois contre les autres et tout contre eux. Enfin, l œuvre laisse apparaître en filigrane l autoportrait d un Américain utilisant la stratégie de l écart dans l habile mise en scène de sa propre iconisation.From the collection A Boy s Will (1913) to the collection In the Clearing (1962), the works of American poet Robert Frost (1874-1963) can be viewed as a reflection on the concept of deviation, presenting it as a major principle in his aesthetics and writing strategy. This doctoral dissertation provides a close reading of many poems, with a view to highlighting the highly seminal quality of the Frostian theme of the slight deviation, which allows one to rethink the dialectic between the center and the margins at different levels of analysis. This dialectic appears not only in the poetic representation of North American space, but also in the established connection between the texts and the metaphorical space of the canon, as well as in the ambiguous presentation of the poetic figure in relation to the intimate, social or political spheres. We wish to show that the poet together with the multiple personae that he uses in the collected poems, favor a specific vantage point, a detached position which is neither in the center nor completely in the margin, but rather within the limits delineated by some deviation. This slightly withdrawn position, which is both dispassionate and perilous, sketches out a triple self-portrait of the poet. It is the self-portrait of an artist for whom the tension between tradition and modernity, between fixed forms and free poetic experiments, creates a complicated but fertile position which allows Frost to position himself both within, and slightly on the margin of, the genre of pastoral poetry. Frost's poems also depict the portrait of a moving poetic figure in the New England landscape, a figure who is put, because of his attempts at settling in certain territories, in a situation where neighbors are both aware and wary of each other. Lastly, the poems could be regarded as the self-portrait of an American posturing as a marginal figure in the skillful staging of his own iconization.TOULOUSE2-SCD-Bib. electronique (315559903) / SudocSudocFranceF

Traitement par azithromycine au long cours dans la mucoviscidose

OBJECTIFS : L'objectif de ce travail est d'évaluer les effets sur la fonction respiratoire, l'état nutritionnel, les exacerbations et les traitements antibiotiques d'un traitement pluri-hebdomadaire par azithromycine au long cours, c'est-à-dire sur une durée de plus de 2 ans, dans une population d'enfants atteints de mucoviscidose. MATERIEL ET METHODE : 54 enfants âgés de 4 à 17 ans, suivis au CRCM de l'hôpital Trousseau à Paris et traités par azithromycine trois fois par semaine depuis au moins 2 ans, ont été inclus dans l'étude. Les données cliniques relatives à leur fonction respiratoire, leur état nutritionnel, leurs exacerbations respiratoires et les traitements antibiotiques ont été relevées annuellement : 12 mois avant la mise en place du traitement puis tous les ans pendant 48 mois. RESULTATS : Nous avons observé un maintient de la fonction respiratoire tout au long de l'étude sans différence au cours du suivi. L'état nutritionnel apprécié par le relevé des indices de masse corporelle est amélioré 48 mois après le début du traitement (p=0,01). Nous n'avons pas observé de diminution du nombre d'exacerbations respiratoires. Le nombre de cures antibiotiques par voie orale diminue de façon significative 48 mois après la mise en place du traitement prophylactique par azithromycine ; mais de façon concomitante à l'augmentation significative du nombre de cures antibiotiques par voie intraveineuse. CONCLUSION : Le traitement prophylactique par azithromycine au long cours permettrait un maintient de la fonction respiratoire ainsi qu'une amélioration de l'état nutritionnel. En revanche, le nombre d'exacerbations respiratoires est inchangé. De plus, le traitement ne semble pas modifier le nombre de cures, bien que le nombre de cures par voie orale diminue, le nombre du cures intraveineuses augmente, correspondant à la prise en charge habituelle de ces patients du fait de l'évolution naturelle de la maladieBLACKGROUND : Macrolides are useful in chronic inflammatory pulmonary diseases, especially in cystic fibrosis, by displaying immunomodularoty effects. The aim of this study is to assess the effects of a long-term treatment with azithromycin on pulmonary function, nutritional status, pulmonary exacerbations and antibiotics treatments in young patients with cystic fibrosis. METHODS : Fifthy four childrens beetwen four and seventeen years old were included. The criteria for inclusion were ; to be followed up at the CF accredited care center of Armand Trousseau hospital (Paris), to be treated with azithromycin since at least two years, to be able to perform reproductible pulmonary tests and produce sputum. Two groups were identified at the inclusion : the group of patients infected by P. aeruginosa and the group of patients not infected. The data relating to pulmonary fonction, nutritional status, pulmonary exacerbations and antibiotics treatments were noted down twelve months before inclusion and then every year. RESULTS : The FEV1 was preserved in the whole population and in the group of non infected patients. The FEV1 failed in the group of infected patients. The BMI was significatively increased at T+48 (p=0,01). There was no decrease of pulmonary exacerbations. Oral antibiotics treatments decreased at the same time as intravenous antibiotics treatments increased (p=0,01 at T+48). CONCLUSION : Long-term treatment by macrolides in young patiens with cystic fibrosis preserve the pulmonary function and especially the FEV1 in those not infected by P. aeruginosa. The nutritional status is also improvedST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Variations saisonnières et circadiennes de la mortalité dans un service de gériatrie

Centre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF