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Inhibition of the macrophage demethylase LSD1 reverses Leishmania amazonensis-induced transcriptomic changes and causes a decrease in parasite load
No full textIntracellular pathogens exploit host cell functions to favor their own survival. In recent years, the subversion of epigenetic regulation has emerged as a key microbial strategy to modify host cell gene expression and evade antimicrobial immune responses. Using the protozoan parasite Leishmania as a model system, we have recently demonstrated that infection causes histone H3 hypomethylation, which is associated with the establishment of an antiinflammatory phenotype, suggesting that host cell demethylases may play a role in the intracellular survival of these parasites. In this study, we combined pharmacological inhibition with RNA sequencing and quantitative immune-precipitation analysis to investigate the role of the macrophage lysine demethylase LSD1 (KDM1a) in Leishmania intracellular infection in vitro. Treatment of infected macrophages with validated, LSD1-specific inhibitors resulted in a significant reduction in parasite burden. We confirmed the impact of these inhibitors on LSD1 activity within macrophage nuclear extracts using an in vitro demethylase assay and established their LSD1 target engagement in situ by cellular thermal shift assay. RNA-seq analysis of infected and inhibitor-treated macrophages linked parasite killing to a partial reversion of infection-dependent expression changes, restoring the macrophage anti-microbial response and limiting cholesterol biosynthesis. While we ruled out any impact of Leishmania on LSD1 expression or localization, we uncovered significant alterations in LSD1 complex formation within infected macrophages, involving unique interactions with host cell regulatory proteins such as Rcor-1. Our study sheds important new light on the epigenetic mechanisms of macrophage immuno-metabolic subversion by intracellular Leishmania and identifies LSD1 as a potential candidate for host-directed, anti-leishmanial therapy
J-NeuS: Joint field optimization for Neural Surface reconstruction in urban scenes with limited image overlap
No full textInternational audienceReconstructing the surrounding surface geometry from recorded driving sequences poses a significant challenge due to the limited image overlap and complex topology of urban environments. SoTA neural implicit surface reconstruction methods often struggle in such setting, either failing due to small vision overlap or exhibiting suboptimal performance in accurately reconstructing both the surface and fine structures. To address these limitations, we introduce J-NeuS, a novel hybrid implicit surface reconstruction method for large driving sequences with outward facing camera poses. J-NeuS leverages cross-representation uncertainty estimation to tackle ambiguous geometry caused by limited observations. Our method performs joint optimization of two radiance fields in addition to guided sampling achieving accurate reconstruction of large areas along with fine structures in complex urban scenarios. Extensive evaluation on major driving datasets demonstrates the superiority of our approach in reconstructing large driving sequences with limited image overlap, outperforming concurrent SoTA methods
Experimental insights into early cement development in carbonate aquifers: from diffusion to surface-controlled calcite growth
No full textInternational audienceDespite their geological significance, the thermochemical processes leading to the formation of early carbonate cements remain elusive. To bridge this knowledge gap, we carried out here laboratory-simulated diagenesis on aragonite ooids. They were placed in autoclaves, filled with distilled water, and subjected to varying temperatures and durations. Our results focus on the transformation from aragonite to calcite with temperaturedependent kinetics. At the grain scale, considered as a thermodynamic system on its own, two distinct stages of microstructural evolution were observed. In the first stage, diffusion processes predominate: the ooids experience progressive dissolution while a fringe of calcite cement forms around their periphery. In a second stage, radial diffusion stops and transformations are dominated by surface-controlled processes, characterized by calcite crystal growth within the ooids. The end-result is generally referred to as "neomorphism" in natural analogues. The transition from the diffusion-dominated to the surface-controlled stage is temperature-dependent and does not occur below 150°C. This behaviour can be explained by the progressive growth of the calcite fringe, which isolates the ooid from the surrounding pore water, while internal aragonite dissolution continues within the grain. These experiments show that early calcite cements, similar to those observed in meteoric phreatic environments, can grow without any external CaCO 3 input. They also show that neomorphism in ooids requires the closure of the ooid system, a condition that can occur at any stage of diagenesis. Finally, our experiments support the presence of a diffusive boundary layer, offering a process-based refinement of the traditional 'thin film' concept
Dissolved organic matter dynamics and chemistry under fungal activity: A microcosm incubation with litter differentially 13C-labelled
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Another India: the making of the world’s largest Muslim minority, 1947–77, by Pratinav Anil, London, Hurst, 2023, 463 pp., £20 (paperback), ISBN 9780197694695
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Cosmological and High Energy Physics implications from gravitational-wave background searches in LIGO-Virgo-KAGRA's O1-O4a runs
No full textInternational audienceWe search for gravitational-wave background signals produced by various early Universe processes in the Advanced LIGO O4a dataset, combined with the data from the earlier O1, O2, and O3 (LIGO-Virgo) runs. The absence of detectable signals enables powerful constraints on fundamental physics. We derive gravitational-wave background energy density upper limits from the O1-O4a data to constrain parameters associated with various possible processes in the early Universe: first-order phase transitions, cosmic strings, domain walls, stiff equation of state, axion inflation, second-order scalar perturbations, primordial black hole binaries, and parity violation. In our analyses, the presence of an astrophysical background produced by compact (black hole and neutron star) binary coalescences throughout the Universe is also considered. We address the implications for various cosmological and high energy physics models based on the obtained parameter constraints. We conclude that LIGO-Virgo data already yield significant constraints on numerous early Universe scenarios
Reimagining coral reef futures
No full textInternational audienceCoral reefs are vital social-ecological systems, but highly vulnerable to global change and local stressors. While conveying the urgency of existential threats is paramount, bleak outlooks can become self-reinforcing, limiting capacities to act. To counter this, experts working on coral reefs in diverse geographies imagined coral reef futures through a structured visioning process. The resulting visions offer alternatives aspiring to desirability, sustainability, and equity for coral reefs. These broaden the conversation on coral reef futures, enabling discussions beyond siloed conservation, traditional management tools, or pure techno-fixes. Concepts such as earth stewardship, biocultural revitalization, and anticipatory governance emerged as essential to sustaining human well-being and enabling the viability of future coral reef ecosystems before, during, and beyond social-ecological shocks. By fostering forward-thinking dialog, these visions and narratives constitute key stepping stones to reimagining desirable relationships between people and coral reefs and speak to both anticipatory and adaptive pathways toward desired change.Coral reefs are among the most biodiverse ecosystems on the planet 1,2 , supporting livelihoods for over 400 million people 3-5 , as well as providing coastal protection 6-8 and other benefits 9 to nearly a billion people. However, they are also among the most vulnerable ecosystems to global change and local anthropogenic stressors 9,10 .By mid-century, projections indicate that coral reefs will be near the brink of biophysical collapse 10,11 , placing the species 2 and societies 9,12 that depend on them under existential threats. Yet, some coral reefs show resistance or resilience to repeated climate impacts 13,14 , exhibit potential to expand into new suitable habitats enabled by climate change 15,16 , and critically, coral reef resilience is largely influenced by local pressures. While global action remains essential to avert the worst effects of climate change, such evidence offers cautious optimism for the future of some coral reef social-ecological systems.Nonetheless, dystopian narratives often dominate coral reef futures conversations 17 . Over time, these narratives become self-reinforcing 18,19 , fueling helplessness without providing actionable solutions 17,20 or overconfidence in technology-based fixes 21 . Even under bleak outlooks, countering such narratives open spaces to reimagine and embrace novel coral reef futures, and to develop anticipatory strategies that maximize coral reefs viability and adaptive capacity in the face of escalating threats 22-24 .Imagining desirable futures (a.k.a. visions 25 ) for people and coral reefs is, however, a creative, cognitive, normative, but necessary,</div
Santé mentale en tension Enjeux épistémologiques, politiques et cliniques d’un espace fragmenté
No full textInternational audienceObjectivesMental health has emerged as a major policy issue at the crossroads of health, political, and ethical concerns. Declared a “national cause” in 2025 and 2026, it is receiving renewed attention while the associated theoretical paradigms and public programs are the subject of intense debate. In this context, an interdisciplinary workshop entitled “Mental Health Policies: Pluralistic Concepts and Perspectives” was held in June of 2025. The event aimed to foster dialogue between researchers, clinicians, and institutional actors regarding the tensions that structure the mental health landscape.Materials and methodsWe report the discussions that took place during this workshop based on an inductive analysis of the exchanges using Braun and Clarke's (2006) method. The corpus, consisting of all interactions, was coded into more than 1700 segments grouped into thematic axes, then manually refined.ResultsFirst, the lack of collective representation of care providers appears to be a persistent consequence of a fragmented health care organization. Care delivery modes and patient populations vary greatly, and the different paths (private practice, community-based care, academic–hospital settings, etc.) often operate in silos. While this diversity reflects initiative and innovation, it does not uphold an unified voice. Second, paradigmatic reframing is considered necessary, integrating prevention, diagnosis, and care. New tools make it possible to articulate biological, clinical, social, or linguistic data without imposing a single overarching model. The objective is to create transparent, interoperable and inclusive methodologies between biomedical, psychodynamic, and social approaches to strengthen user involvement. . Third, in a context of budgetary constraint, it is also crucial to re-allocate funding toward what is most useful for care. This requires identifying financing mechanisms that promote good practices through appropriate incentives and support the many teams engaged in experimentation and evaluation.DiscussionThis workshop shed light on the major forces at play: an acknowledged plurality of approaches, constructive disagreements over evidence-based models, and a shared commitment to tying together the complexity of clinical situations and organizational structures. Its main contribution lies in bringing into dialogue worlds that rarely meet : clinical practice, social sciences, and institutions. The exchanges showed how these perspectives can enrich one another when they are articulated together.ConclusionOur team effort is expected to grow through further meetings , particularly on: (i) research policy issues in mental health (data and commons); (ii) the role of care providers, users, and caregivers in decision-making processes; and (iii) the financing of psychiatry (allocated budgets and psychotherapy coverage).ObjectifsLa santé mentale s’impose comme un enjeu sociétal majeur à la croisée de préoccupations sanitaires, politiques et éthiques. Déclarée « grande cause nationale » en 2025 et 2026, elle fait l’objet d’une attention renouvelée alors que les paradigmes théoriques et les politiques publiques qui s’y rattachent se trouvent au cœur de vifs débats. Dans ce contexte a été organisée en juin 2025 une journée d’étude interdisciplinaire intitulée « Politiques de santé mentale : concepts et perspectives pluriels », rencontre visant à faire dialoguer chercheurs, cliniciens et acteurs institutionnels autour des tensions qui structurent l’espace de la santé mentale.Matériels et méthodesNous restituons les propos tenus dans le cadre de cette journée à partir d’une analyse inductive fondée sur la méthode de Braun et Clarke (2006). Le corpus constitué de l’intégralité des échanges a été codé en plus de 1700 segments regroupés en axes thématiques, avant d’être manuellement retravaillé.RésultatsPrimo, le défaut de représentation des acteurs du soin apparaît le produit persistant de l’organisation du système de santé. Les contextes d’exercice et patientèles divergent, les circuits (libéral, secteur, hospitalo-universitaire, etc.) fonctionnent souvent en silos. Cette diversité, signe d’initiative, a pour revers une dilution du message collectif. Secondo, un refondement paradigmatique est jugé nécessaire, intégrant prévention, diagnostic et soins. De nouveaux outils peuvent articuler données biologiques, cliniques, sociales ou linguistiques, sans imposer un modèle unique. Il s’agit de créer des espaces de partage entre approches biomédicales, psychodynamiques et sociales, de renforcer la participation des usagers, et de s’appuyer sur des méthodologies transparentes, interopérables et inclusives. Tertio, dans un contexte de restriction budgétaire, il semble prioritaire de rediriger les fonds vers ce qui est utile aux soins. Il s’agit d’identifier des modes de financement qui soutiennent les bonnes pratiques, les nombreuses équipes qui expérimentent et évaluent.DiscussionCette journée d’étude a permis de rendre visibles les lignes de force à l’œuvre : une pluralité d’approches assumée, des désaccords argumentés sur les cadres de preuve, ainsi que la volonté partagée de tenir ensemble la complexité des situations cliniques et des organisations. L’apport principal tient à la mise en relation de mondes qui dialoguent rarement dans le même temps : clinique, sciences sociales, et institutions. Les échanges ont montré comment ces registres peuvent s’enrichir mutuellement lorsqu’ils sont articulés.ConclusionNotre collectif est amené à se densifier et de nouveaux temps d’échanges sont prévus, notamment sur : (i) les thématiques des politiques de recherche en santé mentale (données et communs) ; (ii) la place des soignants, des usagers et des aidants dans les processus décisionnaires ; (iii) le financement de la psychiatrie (budgets alloués et remboursement des psychothérapies)