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Inflammatory Signatures in VEXAS Syndrome, Myelodysplasia Cutis, and Sweet Syndrome
No full textInternational audienceImportance VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease caused by UBA1 somatic variants in hematopoietic progenitor cells, mostly involving adult men. It is associated with inflammatory-related symptoms, frequently involving the skin and hematological disorders. Recently described myelodysplasia cutis (MDS-cutis) is a cutaneous manifestation of myelodysplasia in which clonal myelodysplastic cells infiltrate the skin. In both cases, skin lesions are driven by the infiltration of clonal mutated myeloid cells and may clinically and histologically mimic Sweet syndrome (SS), a neutrophilic skin disease. Objective To decipher the underlying mechanisms driving these 3 myeloid-related skin diseases (ie, VEXAS, MDS-cutis, and SS) compared with leukemia cutis (LC), a neoplastic blastic myeloid-related skin condition, and healthy control skin samples. Design, Setting, and Participants This multicenter translational study on formaldehyde-fixed paraffin-embedded lesional skin samples of VEXAS syndrome, MDS-cutis, idiopathic SS, LC, and healthy controls using bulk RNA sequencing analyses was conducted in France. Patients included had cutaneous lesions of VEXAS syndrome, MDS-cutis, idiopathic SS, or LC. The data were analyzed from June 2023 to March 2024. Main Outcomes and Measures Differentially expressed genes between conditions were studied. These genes were used to characterize the enrichment in activated inflammatory pathways in each condition using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis. Results Twenty patients with skin conditions (median [range] age, 67 [43-88] years; 10 [50%] men) were included. Six had cutaneous lesions of VEXAS syndrome, 4 had MDS-cutis, 5 had idiopathic SS, and 5 had LC. They were compared with 5 healthy control skin samples. Bulk RNA sequencing analysis reveals that MDS-cutis and VEXAS syndrome lesions display closely related transcriptomic profiles, highly imprinted by cytokine responses, interferon signatures, and activation of the apoptosis pathway. A shared inflammatory environment between MDS-cutis, VEXAS syndrome, and idiopathic SS was observed, mostly relying on a type 1 immune response led by type 1 and 2 interferons, along with the activation of tumor necrosis factor and interleukin (IL)–1β pathways. Conversely, LC showed an isolated transcriptomic profile mainly enriched in cell cycle pathways. Conclusions and Relevance The findings of this translational study highlight a common inflammatory pattern shared between VEXAS syndrome, MDS-cutis, and refractory idiopathic SS skin samples. This suggests the potential therapeutic targeting of interferon pathways in patients affected with refractory nonblastic myeloid-related skin diseases
Cyclopropyl‐Substituted Trialkoxysilanes and their Related Bis(catecholato)silicates: Preparation, Characterization and Reactivity
No full textInternational audienceHerein, we report a direct route for the synthesis of TMS‐ or ethyl ester‐cyclopropyl trialkoxysilanes and their transformation in bis(catecholato)silicates. Structural analysis of these hypercoodinated λ5 Si‐silicate species was achieved by 1H, 13C, and 29Si NMR, cyclic voltammetry as well as X‐ray diffraction analysis. Their ability to act as a potential cyclopropyl radical precursors was examined experimentally by single electron transfer oxidation via photoredox catalysis. Density functional theory calculations were performed to gain mechanistic insights into their lack of reactivity
Spatial patterning of contractility by a mechanogen gradient underlies Drosophila gastrulation
No full textDuring development cell deformations are spatially organized, however, how cellular mechanics is spatially controlled is unclear. Spatial control of cell identity often determines local cellular mechanics in a two-tiered mechanism ( 1 ). Theoretical studies also proposed that molecular gradients, so called “mechanogens”, spatially control mechanics ( 2, 3 ). We report evidence of such a “mechanogen” required for Drosophila gastrulation. We show that the GPCR ligand Fog, expressed in the posterior endoderm ( 4–6 ), diffuses and acts in a concentration-dependent manner to activate actomyosin contractility at a distance during a wave of tissue invagination. While Fog is uniformly distributed in the extracellular space, it forms a surface-bound gradient that activates Myosin-II via receptor oligomerization. This activity gradient self-renews as the wave propagates and is shaped by both receptor endocytosis and a feedback mechanism involving adhesion to the vitelline membrane by integrins. This exemplifies how chemical, mechanical and geometrical cues underly the emergence of a self-organized mechanogen activity gradient
Nature of momentum- and orbital-dependent magnetic fluctuations in Sr2RuO4
No full textInternational audienc
TIBETOP des paléoaltitudes aux modèles géodynamiques
No full textNational audienceSur les épaules du géant Paul Tapponnier, le projet TIBETOP (ANR 2025-28) étudie la croissance topographique du plateau tibétain pendant la collision Inde-Asie. Malgré des implications majeures sur les processus climatiques, géodynamiques, géomorphiques et biotiques, cette orogènie reste extrêmement controversée. Les débats en cours proposent des modèles radicalement différents de la configuration de la collision, ainsi que de la croissance topographique associée. Nous présentons une compilation de données pour contraindre l'évolution topographique de la zone de collision incluant : i- Âges d'exhumation thermochronologiques (Ar/Ar, traces de fission d'apatite et d'hélium et U-Th/He). ii- Données géochronologiques et géochimiques des roches magmatiques relatives à l'évolution du volcanisme d'arc, à l'épaississement crtustal, etc... iii- Données de paléoélévation (d18O, D47, biomarqueurs, fossiles, etc.) dans une base de données révisée incluant Ding et al., 2022 ; Spicer et al., 2025 et bien d'autres). Cette base de données est fixée à 60, 40, 50, 40, 30, 20 et 10 Ma dans un cadre tectonique des plaques révisé avec de nouvelles configurations de blocs tectoniques, des contraintes géologiques structurales sur le raccourcissement et les décrochements, des données paléomagnétiques indiquant la paléolatitude et la rotation de chaque bloc tectonique et un nouveau chemin de dérive polaire apparent (APWP) global. Ces reconstructions paléogéographiques réalisées avec Terra Antiqua révèlent que les âges de dépôt et les quantités de déplacements enregistrés par les structures du bassin et du socle restent mal contraints et controversés. Malgré ces controverses, de faibles altitudes semblent persister le long des anciennes zones de suture : quels sont les contextes tectoniques pouvant expliquer ces basses altitudes qui ne sont généralement pas associées à une collision continentale? Peuvent-elles être liées à un phénomène roll back et retrait lithospèrique, à une topographie dynamique et/ou à un découplage de la croûte et de la lithosphère continentale en subduction ? Pour tester ces modèles géodynamiques potentiels, les travaux de terrain TIBETOP 2025 visent à identifier les évolutions associées du bassin et du socle
Transmettre le savoir agricole au plus grand nombre : L'exemple du Traité complet d'agriculture (Nōgyō zensho, 1697)
No full textInternational audienceThe transmission of agricultural know-how was a central issue in the economy of Tokugawa Japan (1600–1868). For this regime, whose revenues depended fundamentally on agricultural resources, the consolidation—and even the expansion—of these resources immediately became a major concern. However, the new situation created by the concentration of warriors in castle towns led the warrior elite to lose interest in agricultural labor. At the same time, the dynamism generated by urban development prompted peasants in central regions of Japan to refine their production methods, to specialize, and—together with merchants—to organize supply networks. In part of Japan, this resulted in a “contamination” of the agricultural sphere by commercial logics. The publication of the Complete Treatise on Agriculture (Nōgyō zensho) must be understood within this specific late-seventeenth-century context, in which many domains, faced with financial difficulties, were compelled to reexamine agricultural production techniques.La transmission du savoir-faire agricole est une question centrale dans l’économie du Japon des Tokugawa (1600-1868). Pour ce régime dont les revenus dépendent de manière essentielle des ressources agricoles, la consolidation, voire l’augmentation de ces ressources a représenté d’emblée un enjeu majeur. Cependant, la nouvelle situation créée par le regroupement des guerriers dans les villes castrales a eu pour conséquence le désintérêt de la part de l’élite guerrière pour le travail de la terre. Dans le même temps, la dynamique créée par le développement des villes a conduit les paysans situés dans les zones centrales du Japon à perfectionner les modes de production, à se spécialiser, et à organiser, avec la collaboration des marchands, des circuits d’approvisionnement. On assiste ainsi, dans une partie du Japon, à une « contamination » du monde agricole par des logiques marchandes. La publication du Traité complet d’agriculture (Nōgyō zensho) s’inscrit dans ce contexte particulier de la fin du XVIIe siècle où nombre de fiefs, confrontés à des difficultés financières, sont amenés à se pencher de nouveau sur les techniques de production agricole
Correction: Expansion of forest cover and coeval shifts in Later Stone Age land-use at Taforalt and Rhafas Caves, Morocco, as inferred from carbon isotopes in ungulate tooth enamel
No full textInternational audienceERRATU
Magnetic memory and distinct spin populations in ferromagnetic Co 3 Sn 2 S 2
No full textInternational audienceCo3Sn2S2, a ferromagnetic Weyl semi-metal with Co atoms on a kagome lattice, has generated much recent attention. Experiments have identified a temperature scale below the Curie temperature. Here, we find that this magnet keeps a memory, when not exposed to a magnetic field sufficiently large to erase it. We identify the driver of this memory effect as a small secondary population of spins, whose coercive field is significantly larger than that of the majority spins. The shape of the magnetization hysteresis curve has a threshold magnetic field set by the demagnetizing factor. These two field scales set the hitherto unidentified temperature scale, which is not a thermodynamic phase transition, but a crossing point between meta-stable boundaries. Global magnetization is welldefined, even when it is non-uniform, but drastic variations in local magnetization point to a coarse energy landscape, with the thermodynamic limit not achieved at micrometer length scales
Coupling quantum spin ice to matter on the centered pyrochlore lattice
No full textInternational audienceThe low-energy physics of quantum spin ice is known to support an emergent form of quantum electrodynamics (QED), where magnetic monopoles exist and the fine-structure constant is material dependent. In this article, we show how this QED is modified via a coupling to dynamical matter on the centered pyrochlore lattice, a structure that has recently been synthesized using metal-organic frameworks. Specifically, we study the low-energy properties of the S = 1 / 2 quantum XXZ model on the centered pyrochlore lattice, with a focus on the sign-problem-free region. At fourth order in degenerate perturbation theory, this model hosts a quantum spin liquid distinct from the well-known U(1) quantum spin ice on the pyrochlore because of the presence of dynamical matter in the ground state. Exact diagonalization results are consistent with this quantum spin liquid over an extended region of the ground-state phase diagram, although potential quantum critical points within this region could indicate a richer phase structure. Our work thus expands the physics of quantum spin ice in an experimentally motivated geometry, showing how the emergent QED can be coupled to dynamical matter at zero temperature
« On ne négocie pas sans conditions » : interroger les cadres et modalités des négociations dans les conflits armés
No full textInternational audienceNegotiations are common in armed conflicts. They may involve resolving the entire conflict or focusing on specific issues, such as creating a humanitarian corridor, securing a ceasefire, or deploying a peacekeeping mission. However, negotiation is often costly and uncertain for the involved parties, as these situations are filled with mutual threats that can weaken diplomatic efforts. Therefore, it is crucial to develop a framework and procedures that facilitate effective negotiation initiation and conduct. The design of negotiation frameworks and methods is particularly important because they determine what is at stake, influence the strategic choices of the parties, and shape their interactions. Analyzing these dimensions should provide a better understanding of how mediation and negotiation tend to emerge as the preferred means of resolving armed conflicts, despite the many difficulties associated with the breakdown of traditional diplomatic channels and the lack of trust between the actors involved.Les négociations sont omniprésentes dans les conflits armés. Elles peuvent concerner la résolution du conflit dans son ensemble ou se focaliser sur des aspects spécifiques tels que l’ouverture d’un couloir humanitaire, l’obtention d’un cessez-le-feu ou le déploiement d’une opération de maintien de la paix. Néanmoins, négocier est souvent coûteux et incertain du point de vue des acteurs impliqués, tant ces contextes sont émaillés de menaces réciproques qui limitent l’efficacité de la voie diplomatique. Il est alors indispensable d’instaurer un cadre et des modalités propices à l’ouverture et au déroulement des négociations. Les cadres et modalités des négociations méritent une attention particulière en ce qu’ils déterminent les enjeux, influencent les stratégies des acteurs et structurent leurs interactions. L’analyse de ces dimensions doit permettre de mieux comprendre comment la médiation et la négociation tendent à s’imposer comme des voies privilégiées pour résoudre des conflits armés en dépit des nombreuses difficultés liées à la rupture des canaux diplomatiques habituels et au manque de confiance entre les acteurs concernés