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Is empirical antifungal therapy the next path forward in patients with influenza-associated ARDS?
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Mumps virus infection triggers early pro-inflammatory responses and impairs Leydig and Sertoli cell function in an ex vivo human testis model
No full textInternational audienceStudy question: What is the direct effect of mumps virus (MuV) replication within the human testis on the tissue innate immune responses and testicular cell functions?Summary answer: MuV induces an early pro-inflammatory response in the human testis ex vivo and infects both Leydig cells and Sertoli cells, which drastically alters testosterone and inhibin B production.What is known already: Despite widespread vaccination efforts, orchitis remains a significant complication of MuV infection, especially in young men, which potentially results in infertility in up to 87% of patients with bilateral orchitis. Our understanding of MuV pathogenesis in the human testis has been limited by the lack of relevant animal models, impairing the development of effective treatments.Study design, size, duration: Normal testes were collected from seven uninfected post-mortem donors (median age of 55 years, range 29-79). Organotypic cultures of human testis explants exposed or not to MuV ex vivo were undertaken for 10 days. Utilizing this original ex vivo model, we investigated the replication kinetics of MuV, identified its target cells, characterized the innate immune responses of the testis to the virus, and assessed the impact of the infection on testicular cell functions.Participants/materials, setting, methods: Human testis explants were exposed overnight to MuV at a multiplicity of infection of 1 and cultured on polyethylene terephthalate inserts at the air/medium interface for 10 days. MuV replication in human testis explants was evidenced by measuring the release of infectious viral particles in plaque-forming assay and viral RNA in RT-qPCR, as well as by in situ detection of replicative viral RNA in testicular cells all along the 10-day culture period. Infected cells were characterized by microscopy using specific cell markers and a probe against viral RNA. The innate immune response was assessed using RT-qPCR, in situ hybridization, and LegendPlex. Testosterone and its precursors were measured in the supernatants of MuV and mock-infected explants by mass spectrometry, while inhibin B was measured by ELISA. The impact of MuV infection on testis tissue and cells was further explored by lactate dehydrogenase viability assay, RT-qPCR, immunohistochemistry, and western blot.Main results and the role of chance: MuV robustly replicated in human testicular explants all along the 10-day culture, progressing from the interstitial tissue, where it infected Leydig cells, macrophages, and peritubular cells, to the seminiferous tubules, where it targeted Sertoli cells. Unlike Zika virus, another testis-tropic virus, MuV triggered a pro-inflammatory response within 4 h in exposed human testis explants, characterized by transcriptional upregulation of interleukin 1 beta (IL1B) in sentinel cells. This was followed by the tissue release of inflammatory mediators (P = 0.02 for IL1B at 72 h and Day 7) and the dynamic regulation of interleukin 10 (IL10) upon viral replication. MuV replication inhibited testosterone production from Day 7 onwards (P < 0.03) by disrupting the steroidogenic activity of Leydig cells at the level of cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and decreased inhibin B secretion from Sertoli cells from Day 4 onwards (P < 0.03), which exhibited features of pyroptosis.Large scale data: N/A.Limitations, reasons for caution: This ex vivo study, which demonstrates the direct impact of MuV replication in the human testis, does not assess the additional role of infiltrating peripheral immune cells in testicular lesions.Wider implications of the findings: These findings demonstrate that MuV infection of the human testis elicits a distinct early innate immune response in contrast to Zika virus, known for its silent persistence. This difference offers a potential explanation for the development of MuV-induced testis inflammation. Furthermore, our study provides evidence that MuV directly disrupts crucial testicular functions in the absence of leukocytic infiltrates. These data advance our understanding of the early events of MuV pathogenesis in the testis and provide a basis for further investigation into the mechanisms of orchitis versus silent infection. The ex vivo model of MuV-infected human testis developed in this study will serve as a valuable tool for evaluating antiviral strategies aimed at preserving testicular function in MuV-infected men.Study funding/competing interest(s): This study was supported by grants from the French National Research Agency (grant number ANR-21-CE15-0021-01) and from the Fondation pour la Recherche Médicale (FRM EQU202203014611), as well as by Institut National de la Santé et de la Recherche Médicale and the University of Rennes. The authors have no competing interests.Trial registration number: N/A
Coopérer pour employer : l’employeurabilité des EBE en question(s) ?
No full textInternational audienceL’expérimentation TZCLD aboutit à sa deuxième phase d’expérimentation en 2026. Des démarches d’évaluation ont été engagé par le fonds Territoire Zéro Chômeurs de Longue Durée et la DARES en vue de comprendre l’utilité sociale d’une part et la soutenabilité économique et entrepreneuriale du dispositif d’autre part. Dans le cadre d’une action spécifique financée par l’université Rennes 2 et appuyée par la Maison des sciences humaines de haute Bretagne, le projet de recherche « coopération pour le droit à l’emploi » vise à analyser la spécificité du rôle d’employeur des EBE, qui repose sur l’idée que le chômage provient moins d’un manque d’employabilité des individus que d’une faible employeurabilité des entreprises, ou capacité à gérer les emplois créés.Dans ce cadre, il revient à l’employeur (ici l’EBE ou entreprise à but d’emploi) de créer des emplois ad hoc pour embaucher les chômeurs volontaires (Béraud et Higelé, 2020). Créer un emploi en partant de ce que sait faire l’individu nécessite donc une coopération étroite entre la direction de l’EBE et le salarié. Cette capacité à créer de la coopération constitue à ce titre un des traits distinctifs de l’employeurabilité des EBE.Nos questions initiales seront donc les suivantes : Comment l’EBE et ses salariés coopèrent-ils pour créer l’emploi de ces dernières
Lactuchelins: New lipopeptide siderophores from Pseudomonas lactucae inhibit Xanthomonas campestris pv. campestris 8004
No full textSeeds harbor diverse microbial communities, including beneficial microbes that play a vital role in protecting plants from seed-borne pathogens. Despite their critical importance, the molecular mechanisms driving intermicrobial competition within the seed microbiome remain poorly understood, limiting the potential to optimize seed inoculation strategies. In this study, we evaluated the inhibitory potential of 30 seed-borne bacterial strains against the phytopathogen Xanthomonas campestris pv. campestris 8004 (Xcc8004). We identified Pseudomonas lactucae CFBP13502 as a potent inhibitor of Xcc8004, mediated by exometabolites specifically induced in the presence of Lysobacterales (formerly Xanthomonadales). Transcriptomic analysis of CFBP13502 revealed upregulation of a gene cluster involved in the biosynthesis of a lipopeptide siderophore biosynthesis. Gene deletion confirmed that this cluster is essential for the growth inhibition of Xcc8004. Furthermore, iron supplementation abolished this inhibitory effect, providing strong evidence for the role of iron chelation. Through comparative metabolomics, we elucidated the structure of a novel family of lipopeptide siderophores, which we named lactuchelins, produced by CFBP13502. Our findings provide the first molecular evidence of competitive exclusion mechanisms at the seed microbiome interface, highlighting lactuchelins as a promising avenue for the development of seed-based biocontrol strategies against seed-borne phytopathogens
Social media use and roles of self-objectification, self-compassion and body image concerns: a systematic review
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France National Report for Work Package 2 Skill Partnerships for Sustainable and Just Migration Patterns.
No full textLa poule et le nouvel imaginaire collectif du jardin privatif : la reconstitution d'une basse-cour 3.0
No full textInternational audienceLongtemps on a cru que la poule était dédiée à peupler des méga-poulaillers cachés derrière des haies d'invisibilisation ; la poule de basse-cour de "Martine à la ferme" semblait avoir définitivement disparu ! Or, vers la fin des années 1990 et plus fortement encore au tout début des années 2000, la poule réapparait dans les jardins et jardineries, dans les médias et devient même un animal en peluche à l’occasion de son entrée dans la catégorie des « nouveaux animaux de compagnie » (NAC). La poule accompagne un vaste mouvement de transformation de l'imaginaire du jardin : la pelouse bien tondue et les nains de jardins cèdent la place à des rangs de tomates, à la satisfaction de produire ce que l’on mange… où l’on cultive ses jardins intérieur et extérieur. Cet article montre comment les gallinacées y ont joué un rôle par quatre leviers principaux : 1) la figure du poulet comme symbole d’une agro-industrie prédatrice, 2) la redéfinition du statut social et juridique des animaux, 3) la volonté de prendre en main sa production alimentaire, 4) la sensibilisation au tri des ordures ménagères. Ces 4 dynamiques se déploient à des pas de temps différents, mais se conjuguent entre la fin des années 1990 et le début des années 2000 pour donner corps à la poule dans les jardins d’une société urbanisée
The Role of Reducing and Acidic Hydrothermal Fluids in Forming Chloride Deposits in Terra Sirenum, Mars
No full textInternational audienceAbstract Orbital remote sensing has shown that some regions of the ancient Martian crust contain hundreds of discrete terrains covered by chloride‐rich evaporites. In terrestrial evaporitic systems, evaporite sequences typically begin with the deposition of carbonates, followed by sulfates, and finally chlorides, a depositional sequence that has not yet been found on Mars. Instead, sulfate deposits are always separated spatially and temporally from chlorides, suggesting two different depositional regimes. Here, we present a model driven by the Martian chlorine geochemical cycle that allows the formation of chlorides whilst simultaneously inhibiting sulfate and carbonate precipitation. In this model, the chlorides are produced under reducing and acidic conditions. Chloride deposition was driven by hydrothermal alteration of the Martian crust associated with faults, followed by precipitation from ascending saline solutions along the tectonic conduits. These processes occurred under a relatively thick and reducing atmosphere (1–0.1 bar). The crustal circulation of chloride‐precipitating fluids may have been driven by tectonic suction and pumping processes. Parental brines from hydrothermal activity sourcing chloride might also have contributed to the sulfates found in Cross and Columbus craters of Terra Sirenum. Our study integrates orbital imaging, topography, and spectroscopy with geochemical modeling and terrestrial analogs. We propose that the Terra Sirenum chloride deposits derive from subsurface brines, with deposition driven using tectonic and hydrothermal processes. Under inferred reducing and anoxic conditions, chloride formed with minimal co‐precipitation of sulfates and carbonates. Unlike isolated chloride deposits confined to topographic lows, the Terra Sirenum chlorides are associated with linear features interpreted as faults
The limit shape of the Leaky Abelian Sandpile Model on isoradial graphs
No full textWe study the limit shape of the boundary of the leaky sandpile model on isoradial graphs. These graphs are equipped with conductances and masses introduced by Boutillier, de Tilière and Raschel, which are defined with the help of the geometry of the graph and Jacobi elliptic functions. Building on the link between the shape of the boundary of the sandpile and the Green function of the graph, together with the asymptotics of the Green function obtained by the previously mentioned authors, we prove an explicit formula for the limit shape, both in R^d where the graph can be seen as a monotone surface under our main geometric assumption, and on the plane where it naturally lies. We then study the limit regime where the elliptic modulus, the parameter of elliptic functions, tends to 0, which comes down to approaching the massless case, and obtain a circle as a universal limit shape