Formation of high-valent iron-oxo species in superoxide reductase: characterization by resonance Raman spectroscopy.

International audienceSuperoxide reductase (SOR), a non-heme mononuclear iron protein that is involved in superoxide detoxification in microorganisms, can be used as an unprecedented model to study the mechanisms of O2 activation and of the formation of high-valent iron-oxo species in metalloenzymes. By using resonance Raman spectroscopy, it was shown that the mutation of two residues in the second coordination sphere of the SOR iron active site, K48 and I118, led to the formation of a high-valent iron-oxo species when the mutant proteins were reacted with H2O2. These data demonstrate that these residues in the second coordination sphere tightly control the evolution and the cleavage of the O-O bond of the ferric iron hydroperoxide intermediate that is formed in the SOR active site

Involvement of gut microbial fermentation in the metabolic alterations occurring in n-3 polyunsaturated fatty acids-depleted mice

<p>Abstract</p> <p>Backround</p> <p>Western diet is characterized by an insufficient n-3 polyunsaturated fatty acid (PUFA) consumption which is known to promote the pathogenesis of several diseases. We have previously observed that mice fed with a diet poor in n-3 PUFA for two generations exhibit hepatic steatosis together with a decrease in body weight. The gut microbiota contributes to the regulation of host energy metabolism, due to symbiotic relationship with fermentable nutrients provided in the diet. In this study, we have tested the hypothesis that perturbations of the gut microbiota contribute to the metabolic alterations occurring in mice fed a diet poor in n-3 PUFA for two generations (n-3/- mice).</p> <p>Methods</p> <p>C57Bl/6J mice fed with a control or an n-3 PUFA depleted diet for two generations were supplemented with prebiotic (inulin-type Fructooligosaccharides, FOS, 0.20 g/day/mice) during 24 days.</p> <p>Results</p> <p>n-3/-mice exhibited a marked drop in caecum weight, a decrease in lactobacilli and an increase in bifidobacteria in the caecal content as compared to control mice (n-3/+ mice). Dietary supplementation with FOS for 24 days was sufficient to increase caecal weight and bifidobacteria count in both n-3/+ and n-3/-mice. Moreover, FOS increased lactobacilli content in n-3/-mice, whereas it decreased their level in n-3/+ mice. Interestingly, FOS treatment promoted body weight gain in n-3/-mice by increasing energy efficiency. In addition, FOS treatment decreased fasting glycemia and lowered the higher expression of key factors involved in the fatty acid catabolism observed in the liver of n-3/-mice, without lessening steatosis.</p> <p>Conclusions</p> <p>the changes in the gut microbiota composition induced by FOS are different depending on the type of diet. We show that FOS may promote lactobacilli and counteract the catabolic status induced by n-3 PUFA depletion in mice, thereby contributing to restore efficient fat storage.</p

Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours. Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Modellings of pollen dispersal and estimation from genetic markers

La dispersion du pollen est une composante majeure des flux de gènes chez les plantes, contribuant à la diversité génétique et à sa structure spatiale. Son étude à l'échelle d'un épisode de reproduction permet de comprendre l'impact des changements actuels (fragmentation, anthropisation....) et de proposer des politiques de conservation. Deux types de méthodes basées sur les marqueurs microsatellites estiment la fonction de dispersion du pollen: (i) les méthodes directes (e.g. mating model) basées sur l'assignation de paternité et nécessitant un échantillonnage exhaustif (position et génotype des individus du site étudié, génotypes de graines échantillonnées sur des mères); (ii) les méthodes indirectes (e.g. TwoGener), nécessitant un échantillonnage réduit (génotypes des graines, génotypes et positions des mères) et résumant les données en indices génétiques. Nous proposons la formalisation statistique de ces deux types de méthodes et montrons qu'elles utilisent des fonctions de dispersion différentes: les méthodes directes estiment une fonction forward potentielle (déplacement du pollen depuis le père), les méthodes indirectes une fonction backward intégrative (de la fécondation jusqu'à l'existence du père). Nous explicitons le lien entre fonctions backward et forward, des hypothèses menant à leur équivalence, et des contraintes affectant les fonctions backward. Nous développons enfin une méthode de calcul bayésien approché qui permet (i) une estimation forward, (ii) avec des intervalles de crédibilité, (iii) à partir d'un jeu de données non exhaustif et d'informations partielles (e.g. positions sans génotype) et (iv) l'utilisation de différents modèles de dispersion.Pollen dispersal is a major component of gene flow in plants. It determines to genetic diversity and spatial genetic structure.Studying it at the scale of a single reproduction event enables to understand the impact of current changes (fragmentation, anthropization ...) and to propose conservation practices.Two types of methods, based on microsatellite markers, estimate pollen dispersal functions : (i) direct methods (e.g. mating model) based on paternity assignment require exhaustif sampling (position and genotype of individuals in the study plot, genotypes of seeds harvested on mothers); (ii) indirect methods (e.g. TwoGener), require a weaker sampling (seeds genotypes, genotypes and positions of their mothers) and summarize data through genetic indices.We propose a statistical formalization of both types of methods and show that they rely on different dispersal functions : the direct methods estimate a potential forward function (pollen transfer from the father), whereas the indirect methods estimate an integrative backward one (from fecondation to father existence). We exhibit the link between forward and backward functions, assumptions leading to their equivalence and constrains affecting the backward functions.Finally, we develop an Approximate Bayesian Computation method, which enable (i) a forward estimation, (ii) with credibility intervals, (iii) from a non exhaustive dataset and partial information (e.g. positions without genotypes) and (iv) the use of different dispersal models

Les premiers Jeux olympiques féminins (Paris, 1922): Internationalisme et droit de courir

International audienceWomen's Olympic Games took place in Paris on August 20, 1922, organized by the Frenchwoman Alice Milliat (1884-1957), against the will of the International Olympic Committee and in a context relatively hostile to the practice of sports for women, despite the freedoms obtained in this field since WWI. Bringing together 77 girls from Czechoslovakia, France, Great Britain, Switzerland and the United States around thirteen athletics events, this event could seem anecdotal compared to other events. However, its importance is measured by other criteria: its capacity to reveal a female international, to have encouraged the institutionalization of the sport for the women in the various countries, to have emancipated itself from the hygienic and aesthetic gymnastics in which one confined the girls, but also the violence of the reactions which it generated in the male circles, in particular, of the press and the sport on a national and international scale. While waiting for the imminent vote of the Senate for the female suffrage, the French leaders and sportswomen of August 1922 proclaimed loud and clear their right to run. This first edition will be renewed three times with a growing success, before sinking by the action of the IOC, the International Federation of Athletics and the economic crisis of the 1930s.Des Jeux olympiques féminins ont eu lieu à Paris le 20 août 1922, organisés par la Française Alice Milliat (1884-1957), contre l’avis du Comité international olympique et dans un contexte relativement hostile à la pratique sportive pour les femmes, malgré les libertés obtenues dans ce domaine depuis la Guerre. Réunissant 77 jeunes femmes des États-Unis, de France, de Grande-Bretagne, de Suisse et de Tchécoslovaquie autour de treize épreuves d’athlétisme, cet évènement pourrait sembler anecdotique en comparaison d’autres manifestations plus fournies. Cependant, son importance se mesure à l’aune d’autres critères : sa capacité à avoir fait émerger une internationale féminine, à avoir encouragé l’institutionnalisation du sport pour les femmes dans les différents pays, à s’être émancipé des gymnastiques hygiéniques et esthétiques dans lesquelles on cantonnait les jeunes filles, mais aussi la violence des réactions qu’il a générées dans les milieux masculins, en particulier, de la presse et du sport à l’échelle nationale et internationale. En attendant le vote imminent du sénat pour le suffrage féminin, les dirigeantes et sportives françaises d’août 1922 clament haut et fort leur droit de courir. Cette première édition sera renouvelée trois fois avec un succès croissant, avant de sombrer par l’action du CIO, de la Fédération internationale d’athlétisme et de la crise économique des années 1930

Problématiques et enjeux du mouvement olympique depuis Pierre de Coubertin

Le mouvement olympique, aujourd’hui plus que séculaire, a passé l’épreuve du XXe siècle en se confrontant aux deux conflits mondiaux, aux dictatures des années 1930 ou encore à la longue guerre froide, et en profitant d’un contexte culturel favorable à l’avènement des loisirs, en particulier sportifs, et des médias. Pourtant, le succès des Jeux, renouvelé tous les quatre ans, ne doit pas occulter les nombreux obstacles qu’ont dû surmonter les successeurs du fondateur pour assurer la continuit..

Les cultures corporelles et sportives des femmes au pouvoir de Golda Meir à Angela Merkel

International audience“Body and Sporting Cultures of Women in Power, from Golda Meir to Angela Merkel”The aim of this paper is to study the making and the use of the body and sporting cultures of four women, each Head of their respective state. Golda Meir (1898-1978), Indira Gandhi (1917-1984), Margaret Thatcher (1925-2013) and Angela Merkel (born in 1954) are three generations of women in three different moments of the history of sport: its emergence at the end of the 19th century, its development in the Interwar period and its massification since the 1960s. The analysis of several biographies and press reviews shows that their social background and education built both their vision of sport, which were in fact their father’s one, and their body culture, influenced by their mother. Women in power did not escape from gender stereotypes, which apply in sport and political areas. Whereas they did no or few sport, they improvised as supporters when political reasons required it.L’objet de cet article est d’étudier la fabrique et l’usage des cultures sportives et corporelles de quatre femmes qui ont été à la tête de leur État. Golda Meir (1898-1978), Indira Gandhi (1917-1984), Margaret Thatcher (1925-2013) et Angela Merkel (née en 1954) forment trois générations qui correspondent aussi à trois temps de l’histoire du sport : son émergence à la fin du XIXe siècle, son développement dans l’entre-deux-guerres et sa massification à partir des années 1960. L’étude des différentes biographies et revues de presse montre que le milieu social et l’éducation construisent un rapport au sport venant du père et une culture corporelle influencée par la mère. Les femmes au pouvoir n’échappent pas aux stéréotypes de genre qui prévalent dans le sport et dans la politique. Pas ou peu pratiquantes, elles s’improvisent supportrices quand la raison politique l’exige