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Effets différenciés des modalités utilisées lors de l’imagerie dynamique sur la performance au service au tennis
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PEGASUS : Prédiction de la flexibilité des protéines dérivées de MD à partir de la séquence
No full textInternational audienceProtein flexibility is essential to its biological function. However, experimental methods for its assessment, such as X‐ray crystallography and nuclear magnetic resonance spectroscopy, are often limited by experimental variability and high cost, leading to a gap between the number of identified protein sequences and the available experimental information on protein dynamics. On the other hand, molecular dynamics (MD) simulations provide a uniform and detailed description of the expected protein flexibility, and the availability and quality of such data are increasing significantly during the last years. In this study, we use the recently released ATLAS database to develop ProtEin lanGuAge models for prediction of SimUlated dynamicS (PEGASUS), a sequence‐based predictor of MD‐derived information on protein flexibility (https://dsimb.inserm.fr/PEGASUS). PEGASUS integrates four different representations of protein sequences generated by Protein Language Models to predict residue‐wise MD‐derived values of backbone fluctuation (root mean square fluctuation), Phi and Psi dihedral angles standard deviation, and average Local Distance Difference Test across the trajectory. The PEGASUS web server was optimized to perform instantaneous predictions for an individual protein sequence and also allows batch submission of up to 100 sequences of 1k residues each. For more complex queries, we also release PEGASUS as a user‐friendly standalone utility ( https://github.com/DSIMB/PEGASUS ).La flexibilité des protéines est essentielle à leur fonction biologique. Cependant, les méthodes expérimentales d'évaluation, telles que la cristallographie aux rayons X et la spectroscopie par résonance magnétique nucléaire, sont souvent limitées par la variabilité expérimentale et le coût élevé, ce qui entraîne un écart entre le nombre de séquences protéiques identifiées et les informations expérimentales disponibles sur la dynamique des protéines. En revanche, les simulations de dynamique moléculaire (DM) fournissent une description uniforme et détaillée de la flexibilité protéique attendue, et la disponibilité et la qualité de ces données ont considérablement augmenté ces dernières années. Dans cette étude, nous utilisons la base de données ATLAS, récemment publiée, pour développer des modèles de langage protéique pour la prédiction de dynamiques simulées (PEGASUS), un prédicteur séquentiel des informations dérivées de la DM sur la flexibilité des protéines (https://dsimb.inserm.fr/PEGASUS). PEGASUS intègre quatre représentations différentes de séquences protéiques générées par des modèles de langage protéique afin de prédire les valeurs dérivées du modèle de distribution moyenne (MD) résidu par résidu de la fluctuation du squelette (fluctuation quadratique moyenne), de l'écart type des angles dièdres Phi et Psi, et du test de différence de distance locale moyen sur la trajectoire. Le serveur web PEGASUS a été optimisé pour réaliser des prédictions instantanées pour une séquence protéique individuelle et permet également la soumission par lots de jusqu'à 100 séquences de 1 000 résidus chacune. Pour les requêtes plus complexes, nous proposons également PEGASUS sous forme d'utilitaire autonome et convivial (https://github.com/DSIMB/PEGASUS)
Reimagining Long-Term Care in Sub-Saharan Africa: The Potential of the Foster Family for Dependent Older Adults Model
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Sickle Cell Diastolic Cardiomyopathy and Mortality Risk: A Novel Echocardiographic Framework for Prognostic Stratification
No full textInternational audienceABSTRACT Cardiovascular complications are the leading cause of mortality in sickle cell anemia (SCA) patients. While extensive data have identified diastolic dysfunction (DD) to increase morbidity and mortality, the unique hemodynamic conditions inherent to SCA challenge the current recommendations to assess diastolic function. Thus, there is an urgent need to refine the echocardiographic definition of DD to improve risk stratification and therapeutic strategies in SCA patients. We analyzed data from the French multicentric Etendard cohort and compared them with an age‐ and sex‐matched control group from the Copenhagen City Heart Study (CCHS). We focused on left ventricular diastolic parameters, specifically lateral e′ velocity (e′ lat), E/e′ ratio, and indexed left atrial volume (LAVi), assessing their association with clinical outcomes over a 12‐year follow‐up. Etendard SCA patients ( n = 379) had an early impaired diastolic function compared to the CCHS controls ( n = 672). This was particularly obvious in young SCA patients ( n = 252, age ≤ 38 years) in whom e′ lat was associated with prognosis ( p = 0.01), with an optimal cut‐off value below 11 cm/s. Indeed, young SCA patients with DD had a fourfold increased 12‐year mortality rate as compared with SCA patients without DD (16 vs. 4%, p < 0.001). Additionally, e′ lat correlated with 6‐min walk test, NT pro‐BNP levels, diastolic blood pressure, and lactate dehydrogenase levels. In young SCA patients, our data contribute to refine the diagnosis of diastolic dysfunction evaluation. We highlight the prognostic value below 11 cm/s of lateral e′ velocity and its association with key contributors of cardiac impairment such as hemolysis and systemic vasculopathy. Trial Registration: ClinicalTrials.gov identifier: NCT0043490
Familial cardiac laminopathy with predominant atrial involvement: a case series of a family with LMNA mutation
No full textInternational audienceAbstract Background We present a case series detailing a family with familial cardiac laminopathy, including the female index patient, her father, her brother, and her daughter, all diagnosed with atrial arrhythmias, i.e. atrial fibrillation (AF), atrial flutter, and atrial premature contractions. Case summary The index patient is known for frequent premature atrial contractions since the age of 35 years and for persistent AF since the age of 46 years. Rhythm control of symptomatic AF was achieved after two ablations. The brother of the index patient is known for asymptomatic persistent AF since the age of 26 years. He has opted for rate control and oral anticoagulation. Their father had persistent AF for many years before his death. The daughter of the index patient has asymptomatic frequent premature atrial contractions. She is under medical surveillance without specific medical treatment. All four patients have a normal ventricular systolic function. Genetic testing revealed a heterozygous missense variant in the LMNA gene causing a familial form of cardiac laminopathy, with clinical predisposition to atrial arrhythmias. Discussion The familial occurrence of atrial arrhythmias without significant ventricular involvement in several family members with heterozygous LMNA missense mutation underscores the potential genetic component in cardiac arrhythmias, especially if arrhythmias occur in younger individuals without common risk factors
"Peuplement et main-d’œuvre en Guyane : pistes de recherches sur l’immigration martiniquaise des années 1930"
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Adresser les enjeux de sécurité alimentaire dans les espaces périphériques marginalisés
No full textInternational audienceContexte La conférence de Rio en 1992 consacre la reconnaissance internationale de la spécificité d’États et territoires au prise de leurs vulnérabilités structurelles exacerbées. Il s’agit des petites économies insulaires, espaces périphériques marginalisés (EPM) par excellence, qui affichent en commun certaines caractéristiques : petite taille, discontinuité spatiale, éloignement des marchés internationaux, faible diversification économique, dépendance extérieure, et exposition aux risques globaux (économiques, géopolitiques, environnementaux, sociétaux et technologiques). Ces facteurs structurels sont couramment appréhendés comme des déterminants de leurvulnérabilité (Angeon et Hoarau, 2015; Guillaumont et al., 2020) bien que ces économies demeurent hétérogènes (Angeon et Bates, 2015a). En particulier, se pose la question du rôle du secteur agricole dans leur vulnérabilité (Angeon et Bates, 2015b; Blancard et al., 2020) et de son impact sur leur sécurité alimentaire.Objectif Cet article actualise le débat sur la vulnérabilité des EPM en considérant l’angle de la sécurité alimentaire. Il appréhende la manière dont les caractéristiques dites structurelles de ces espaces impactent leur sécurité alimentaire dans un contexte de changements globaux exacerbés. Pour cela, une approche en termes de nexus agriculture-alimentation-environnement-santé (Axelos et al., 2020) est proposée. Elle permet d’en connecter les différentes composantes tout en considérant la complexité des interactions mais également les synergies possibles au sein du système alimentaire. Une telle approche conduit à croiser différents courants de littérature pouranalyser les modèles agricoles et alimentaires contemporains et leurs impacts économiques, sociaux, environnementaux et sanitaires
Implication du propriétaire familial dans la TPE et responsabilité environnementale. La religiosité joue-t-elle un rôle ?
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Clinical, Phenotypic and Genotypic Characteristics of Von Willebrand Disease in Afro‐Caribbeans: Results From a Study in Martinique Island, French West Indies
No full textInternational audienceABSTRACT Background Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); very few have focused on the Afro‐Caribbean population. Objectives To determine the genotypic and phenotypic characterization of VWD in a large cohort of Afro‐Caribbean patients living in Martinique. Materials and Methods A total of 31 families comprising 63 Afro‐Caribbean patients with VWD were enrolled. A standardized questionnaire and blood samples were collected for biological and molecular genetic analyses of von Willebrand factor (VWF). The impact of new missense variants has been predicted by in silico studies. Results The median age of patients was 53 years (range 9–99). The most frequent symptoms were menorrhagia (49%), easy bruising (44%) and prolonged bleeding after tooth extraction (42%). Fifteen patients (24%) had quantitative deficiencies of VWF, of whom 13 (21%) were assigned as VWD‐type 1, 1 (1%) as VWD‐type 1C and 1 (2%) as VWD‐type 3. Forty‐five patients were diagnosed with VWD‐type 2 (qualitative defects of VWF) (71%). VWD‐type 2A was the most frequent, with 36 patients. Seven patients had VWD‐type 2M and two patients had VWD‐type 2B. Three patients (5%) had an indeterminate effect of the VWF defect due to ISTH BAT at 0. Forty‐eight different VWF variants, including 4 novel variants, were identified in 63 patients. The variants consisted of 34 (71%) missense, 7 (15%) synonymous, 3 (6%) frameshifts, 2 (4%) small deletions and 2 (4%) gene conversions. Conclusions This study emphasizes the unique distribution of genotypes in our cohort of Afro‐Caribbean VWD patients living in Martinique. Essentials Genotype‐phenotype correlation was assessed in VWD Afro‐Caribbean patients with one or more VWF variants. Menorrhagia, easy bruising and prolonged bleeding after tooth extraction are common in VWD patients. Efforts to increase the awareness and diagnosis of VWD have contributed to a better identification of patients with bleeding disorders