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Targeting Langerhans cells via skin delivery of HIV Envelope enhances the antibody response to vaccination
No full textInternational audienceTargeting dendritic cells (DCs) with antigens is a promising approach to modulating T follicular helper (Tfh) cells and germinal center (GC) reactions, enhancing vaccine-induced adaptive immune responses, with preclinical studies highlighting a key role of Langerhans cells (LCs) in generating HIV-1-specific antibody responses. This study evaluated the immunogenicity of a Langerin-targeting vaccine (αLang.Env), comprising an anti-mouse Langerin mAb fused to HIV-1 Envelope 96ZM651 gp140 (Env), delivered through various skin immunization routes in mice, and explored the roles of epidermal LCs and dermal cDC1s in adaptive immune responses. Lymph nodes draining the immunization sites were analyzed using ovalbumin (OVA) as a surrogate antigen after topical (top.), subcutaneous (s.c.), intradermal (i.d.), or transcutaneous (t.c.) delivery via laser-guided microporation, with αLang.Env administered without adjuvant in a Prime-Boost scheme. All methods primed T cells in draining lymph nodes (dLN), as shown by OVA-specific CD8 + and CD4 + T cell proliferation, while αLang.Env induced GC B cells regardless of the route. However, topical delivery did not elicit Tfh cells or Env-specific GC B cells, whereas i.d. and s.c. routes produced systemic Env-specific IgG responses, with i.d. immunization yielding the highest titers and strongest Tfh responses. In the Xcr1 DTA mouse model, where cDC1s were depleted, the i.d. route confirmed that epidermal LCs were the primary drivers of GC/Tfh reactions and humoral responses, while cDC1s mediated CD8 + T cell effector responses. These findings highlight that i.d. administration of the HIV-1 Env antigen targeted to Langerin, without the use of an adjuvant, is an effective vaccine strategy for eliciting GC reactions in LN and generating robust antibody responses, primarily through the activation of LC
Clusters of resonances for a non-self adjoint multichannel discrete Schrödinger operator
No full textInternational audienceWe study the distribution of resonances for discrete Hamiltonians of the form H0 + V near the thresholds of the spectrum of H0. Here, the unperturbed operator H0 is a multichannel Laplace type operator on ℓ2(Z;CN)≅ℓ2(Z)⊗CN and V is a non-selfadjoint compact perturbation. We compute the exact number of resonances and give a precise description on their location in clusters around some special points in the complex plane
From the classical "three-pillars" vision of sustainability to new frameworks for assessing the effects of farming systems enhancing poultry welfare
No full textSession 75. Sustainability assessment of livestock farming systemsInternational audienceLivestock farming systems (LFS) face numerous environmental, social, and economic challenges, all encompassedby the concept of sustainability. Over the past two decades, the scientific community has developed manymethods and tools to assess LFS sustainability (e.g., the OVALI method for poultry). These multicriteria approachesare built on several theoretical and methodological considerations, such as designing the conceptualframework, weighting the criteria, or aggregating the results. In the past decade, societal concerns regardinganimal welfare (AW) in the poultry sector have risen sharply. Consequently, evaluating the effects of practices designedto improve AW, on various sustainability criteria (e.g., production costs, labour, environmental footprint)has been a significant challenge for researchers and stakeholders. For instance, in conventional chicken production,the COCORICO method introduced a new conceptual framework that departs from the traditional three-pillarsview of sustainability. In this method, animal-friendly practices implemented in chicken farms (e.g., the EuropeanChicken Commitment) are indeed evaluated across four pillars: AW, economy, environment, and farmer.Similarly, scientists involved in the European Partnership Animal Health & Welfare are developing since 2024 ageneric framework to assess, in all livestock species, the impacts of practices enhancing AW. This goal, however,raises several challenges. Firstly, experts from various disciplines and different livestock sectors must agree on ashared vision of sustainability. Secondly, methodological choices must be addressed, in particular those regardingthe weighting and/or the aggregation of results. These experiences underscore that each multicriteria assessmentframework is unique and results from a lengthy, complex process involving many methodological considerationsand choices. This work was co-funded by the European Union’s Horizon Europe Project 101136346 EUPAHW
Clinical Presentation and Outcomes After Surgery for Mitral Regurgitation: Real-World Insights From the MITRACURE International Registry
No full textInternational audienceBackground: Comprehensive knowledge of the clinical presentation, contemporary management, and outcomes on "allcomer" patients referred for mitral valve surgery (MVS) are critical to evaluate current practice and adherence to guidelines, understand selection biases, and inform key stakeholders on quality improvement. Methods: MITRACURE is a large international retrospective registry of consecutive adult patients who underwent isolated or combined MVS for mitral regurgitation (MR) in France or Canada in 2019 with in-depth clinical and echocardiographic characterization. Patients operated on for isolated mitral stenosis or who had a prior mitral valve intervention were excluded. Data were obtained from detailed chart abstraction and were site reported. Results: In 2019, 3522 patients underwent MVS (48% combined) across 40 centers (88±46 MVSs/center, median 80, interquartile [51–131]). Mean age was 65±12 years, and 35% were women. The most common MR etiology was myxomatous (61%), followed by functional (9%), infective endocarditis (9%), and rheumatic disease (7%). MR quantification was performed in only 43%. Advanced clinical presentation was common: 43% were in New York Heart Association class III/IV, 30% exhibited congestive heart failure, 47% were on diuretics, 22% had atrial fibrillation/flutter, 35% presented with reduced ejection fraction, and 22% had pulmonary hypertension (≥50 mm Hg). Most patients were symptomatic or presented with class I/IIa indication for intervention, and an early intervention was performed only in 3% of patients. The repair rate was 62% overall and 80% in myxomatous disease. In-hospital mortality was 4.5% overall but 2.3% in patients with myxomatous MR (1.8% isolated, 3.1% combined). Conclusions: MITRACURE provides a contemporary, multicenter, "real-world" picture of the clinical presentation, management, and in-hospital outcomes of MVS for MR in two Western countries. Patients were often referred late in the disease process, with few patients undergoing early intervention. The higher mortality and lower repair rates reported may be more reflective of an unselected MR patient population but have room for improvement. Our results underline the need to develop strategies to improve management and outcomes of patients with MR
Rapport de conjoncture 2025 - Section 39 Espaces, territoires, sociétés
No full textLa communauté scientifique de la section 39 étudie la dimension spatiale des phénomènes sociaux. Elle éclaire ainsi réciproquement l'organisation, le fonctionnement et l'évolution des territoires en prenant en compte la complexité de l'inscription des sociétés dans leurs environnements à différents niveaux géographiques. Le rapport est organisé en deux parties. Il s'intéresse (1) aux structures et personnels de recherche. 76 unités relèvent à titre principal ou secondaire de la section auxquelles sont rattachés près de 3000 personnels statutaires (dont, pour le CNRS, 317 chercheur.e.s et 313 personnels d'appui à la recherche) et environ 2600 personnels non permanents. Ces derniers, très majoritaires au sein des personnels d'enseignement-recherche parmi les 30-40 ans, continuent de représenter 40% des emplois parmi les 40-44 ans. La pyramide des âges inversée des personnels d'appuis à la recherche atteste de l'affaissement des recrutements au cours des 20 dernières années et du vieillissement important des corps d'ingénieur.e.s et de technicien.ne.s. 160 chercheurs et chercheuses relèvent directement de la section 39, la plus féminisée du CNRS (à 49%). Entre 2018 et 2023, 21 chargé.e.s de recherche de classe normale ont été recruté dans une tendance générale à la baisse. Les conditions d'exercice dans les laboratoires de la section sont marquées par l'importance désormais généralisée des financements sur projets. Les résultats de l'enquête conduite au sein de la communauté de la section pour saisir les conditions de recherches (184 réponses reçues) donne à voir l'inflation du temps d'administration et de gestion de projet qui vient entraver le temps consacré aux recherches et à sa valorisation notamment en raison de la réduction sensible des personnels d'appui. La sensibilité aux inégalités de genre et à la prise en compte du handicap au travail est largement partagée en dépit de la difficulté des institutions de tutelles à les prendre pleinement en charge.Le rapport dresse (2) un état des thématiques et approches qui animent la section. Une analyse des axes affichés par les UMR permet de décrire les champs d'étude des laboratoires autour de clusters thématiques : sociétés / environnement ; fabrique urbaine ; villes / espaces de vie ; territoire / frontières / pouvoirs ; politiques publiques / emplois / durabilités. L'analyse des titres des thèses donne des indications sur les différents sous-champs des recherches les plus actuelles. L'enquête conduite auprès de la section confirme la longue habitude de travail sur des terrains multiples en jouant de logiques d'analyse multiscalaires. On constate un certain recul des approche aréales en même temps qu'une tendance importante à croiser des terrains proches et lointains notamment à l'échelle de l'Europe et dans le cadre de coopération internationales. Le rapport signale toutefois des empêchements nouveaux liées à la fermeture ou à la difficulté d'accès de certains terrains à l'étranger. La section confirme son double ancrage dans les méthodes qualitatives (entretiens, observation, participation) et quantitatives (y compris la modélisation spatiale) et la grande fréquence des couplages quali-quanti ; on voit aussi grandir l'intérêt pour les valorisations alternatives des résultats de recherche, l'émergence de démarches au croisement de l'art et de la science, ainsi que la monté en puissance des préoccupations éthiques. Des niches méthodologiques apparaissent faisant un usage informé de l'IA. On repère aussi dans les réponses à l'enquête une diffusion croissante des pratiques de la science ouverte. Place est faite enfin dans le rapport aux vécus collectifs et individuels des périodes covid et post-covid dans la vie des laboratoires.Le rapport souligne en conclusion l'importance et la vitalité des UMR qui font vivre la recherche dans les périmètres thématiques de la section 39. Ils constituent autant d'écosystèmes scientifiques locaux, interdisciplinaires, non hiérarchisés, essentiels à la formation et au déploiement de nouvelles questions de recherche d'envergure nationale et internationale
L’empreinte du corps en mémoire épisodique : le rôle du répertoire moteur dans l’observation d’actions chez les adultes jeunes et âgés
No full textInternational audienc
Comprehensive mapping of transcription terminator Rho utilization (Rut) sites across the Bacillus subtilis genome
No full textInternational audienceAbstract Recent evidence indicates that the bacterial Rho helicase regulates Bacillus subtilis gene expression in a growth-dependent manner. This regulation, along with extensive in vivo trimming of Rho-dependent transcript 3′-ends, complicates the identification of Rho-dependent transcription terminators using standard transcriptomic approaches. To overcome this challenge, we applied Helicase-SELEX to precisely map Rho utilization (Rut) sites genome-wide. Using B. subtilis Rho (BsRho), we identified 600 putative Rut sites, while the more permissive Escherichia coli Rho (EcRho) revealed 4189 sites, including specimens known to regulate B. subtilis genes. Comparative analysis showed that both enzymes recognize similar pyrimidine-rich sequences, though BsRho favors short unstructured Rut motifs whereas EcRho can act on presumably more structured RNAs without requiring accessory factors. In vivo validation of selected Rut sites confirmed Rho-dependent regulation and extensive PNPase-mediated processing of Rho-terminated transcripts. Collectively, our results reveal a rich and complex Rho-dependent regulatory network in B. subtilis, encompassing the widespread control of antisense transcription and genes/operons of both primary and secondary metabolism. Although nonessential under standard laboratory conditions, Rho thus likely contributes to B. subtilis fitness and survival in more demanding environments. Our comprehensive compendium of Rut sites offers a valuable resource for exploring this adaptive regulatory landscape
Signaling Information into Storybooks: The Effects on Preschool Children’s Comprehension
No full textInternational audienceThe purpose of the present study was to investigate the effects of the presence of illustrations, combined with those of signaling, on preschool nonreader children’s memorization and comprehension of a storybook. A total of 82 children (5–6 years old, last year of nursery school) took part in the study. They heard a prerecorded narration, either without illustrations (control group), with illustrations and without elements circled, or with illustrations and graphical signals (elements circled in the illustrations). Following our expectations, the results revealed that adding illustrations to the narration improved the children’s memorization and comprehension of the story (multimedia effect). Moreover, a positive effect of signals was also observed on the children’s memorization and comprehension scores. This study is the first to investigate the effects of illustrations, combined with those of signaling, on preschool nonreader children in a naturalistic environment. The findings suggest that illustrations and signals should be used to promote illustration processing and to heighten young children’s learning