Portail HAL du Collège de France
Not a member yet
22122 research outputs found
Sort by
Le pape François, une vision résolument ouverte de l’art, pour tous et sous toutes ses formes: Entretien avec Juliette Bénabent et Rémi Guezodje
No full textInternational audienc
Heterozygous RAB3A variants cause cerebellar ataxia by a partial loss-of-function mechanism
No full textInternational audienceAbstract RAB3A encodes a small GTP-binding protein that is abundant in brain synaptic vesicles and crucial for the release of neurotransmitters and synaptic plasticity. Here, we identified RAB3A as a candidate gene for autosomal dominant cerebellar ataxia by two independent approaches: linkage in a large dominant ataxia family and, in parallel, an untargeted computational genetic association approach, analysing the 100 000 Genomes Project datasets. To validate the role of RAB3A in ataxia, we next screened large rare disease databases for rare heterozygous RAB3A variants in probands with ataxia features. In total, we identified 18 individuals from 10 unrelated families all sharing a cerebellar ataxia phenotype. Notably, 9 of the 10 families carried a recurrent variant in RAB3A, p.Arg83Trp, including one de novo occurrence. In addition, our screening revealed three families with a neurodevelopmental phenotype and three unique RAB3A variants, which were either de novo or loss-of-function variants. In line with the different RAB3A variant types, protein domains and predicted functional consequences, a comprehensive set of complementary methods was used to characterize the identified variants functionally. As expected, GTPase-activating protein (GAP)-dependent GTP hydrolysis was reduced for those two missense variants located in the GAP-binding domain of RAB3A (Arg83Trp and Tyr91Cys). In a Drosophila Rab3 loss-of-function model, these two missense variants also failed to rescue a synaptic phenotype. Overexpression of Rab3 variants in Drosophila wild-type background did not cause an obvious phenotype, making a dominant negative effect of these variants unlikely. Lastly, exploring interactors of RAB3A variants by using co-immunoprecipitation and mass spectrometry showed differential changes in variant-specific interactions with known RAB3A key regulatory and effector proteins. In sum, our results establish RAB3A as a neurological disease gene. It represents an autosomal dominant gene for cerebellar ataxia with different variants associated with disease, including the frequent reoccurring variant p.Arg83Trp. Our study sheds light on the variant-specific interactome of RAB3A. Finally, we suggest an association of RAB3A with a neurodevelopmental phenotype, as reported for variants in several RAB3A interaction partners and as seen in Rab3A-deficent mice, although this possible association warrants further investigation by future studies
Dissipative phase transition of interacting non-reciprocal fermions
No full textWe study an interacting fermionic chain in the presence of non-reciprocal gain and loss processes obtained via reservoir engineering. The interplay between unitary evolution and the two dissipative processes leads to distinct non-reciprocal signatures in the transient dynamics and the steady state. These include a transition from exponential to power-law relaxation towards a finite-density steadystate, a nonzero particle current from breaking inversion symmetry, and dynamics under open boundary conditions showing directionality and charge accumulation. Weak interactions preserve the main signatures of non-reciprocity, enriching the interacting many-body non-reciprocal phase with volume law entanglement of quantum trajectories. Upon increasing the interaction above a critical value, we find a dissipative phase transition where reciprocity is dynamically restored.</div
Evidence for Neolithic acquisition of the high pathogenic island by Escherichia coli followed by recent selection
No full textAbstract Many genetic elements involved in virulence and pathogenicity have been identified in commensal bacteria that are also opportunistic pathogens, but how these elements evolve is less well known. Understanding the evolutionary history of virulence elements requires genomes sampled in commensalism in healthy hosts, as genomes from bacterial infections are biased towards higher pathogenicity. Here, using a rare collection of human commensal Escherichia coli sampled in France from 1980 to 2020, we inferred the evolutionary history of the High Pathogenicity Island (HPI), a key virulence factor of E. coli with an uncertain evolutionary origin. We showed that the HPI was horizontally transferred from Yersinia pestis to E. coli and other Enterobacterales approximatively 4,800 years ago, coinciding with a period of high prevalence of the plague in the Neolithic. The element subsequently spread in the whole species and in Klebsiella pneumoniae , with signs of positive epistasis with phylogroups B2 and F, and was positively selected in the last 100 years. Our work sheds light on the history and mode of evolution of virulence in an important opportunistic pathogen. It suggests the Neolithic period may have favored not only the emergence of zoonotic pathogens but also gene transfer between bacterial species, enriching the gene repertoire of major pathogens with potentially important implications on public health nowadays
Astroglial regulation of critical period plasticity in the developing brain
No full textInternational audienceAstrocytes emerge as pivotal regulators of brain plasticity during critical periods (CPs) of development. Beyond their traditional roles in supporting neuronal function, astrocytes actively shape synaptic circuits maturation and remodeling during postnatal experience-dependent plasticity. Through mechanisms such as regulation of the extracellular matrix or synaptic pruning, astrocytes influence the timing and extent of plasticity across sensory and cognitive systems. These processes have been demonstrated in various animal models and forms of plasticity, indicating that these glial cells play a conserved role across species. Such findings unveil the dynamic and central role of astrocytes in coordinating the complex interplay between neural circuits and external stimuli during critical windows of brain development
A group of merging galaxies falling onto Abell 2142
No full textGalaxy clusters produce a very hostile environment to galaxies, whose gas gets stripped by ram-pressure, suffer galaxy interactions and witness quenching of their star formation. Clusters continue their growth not only through galaxy accretion but also through galaxy group infall, such as Abell 2142, directly connected to the cosmic web. Our goal is to study the physical and dynamical state of the most conspicuous infalling group, on a filament projected at 1.3 Mpc from the Abell 2142 center. The galaxy group is the leading edge of a spectacular trailing X-ray tail, 700 kpc in length, of hot gas stripped by ram-pressure. The infalling galaxies are not yet quenched, and they are ideal objects to study the transformation processes due to the cluster environment. We use integral field spectroscopy from MaNGA to derive stellar and gas kinematics, and MegaCam for ugr photometry. Stellar populations (with age and metallicity) are obtained through full-spectrum fitting using Nburst. The gas kinematics and excitation are derived from the line emission of Hα, [NII], [OIII] and Hβ. The group contains four galaxies, of which two are merging, and partly superposing on the line of sight. With a simple parametric model for each velocity field, we succeed in disentangling the contribution of each galaxy, and derive their physical state and kinematics. The galaxies are perturbed and intra-group gas is observed as tidal tails and loops. They are mainly disks in rotation, although some regions reveal elevated dispersion, typical of out of equilibrium gas. All galaxies show sustained star formation, with a global star formation rate of 45 M ⊙ /yr. We conclude that the long X-ray tail must have come from the hot intra-group medium, present before the group infall, and does not correspond to the ram-pressure stripping of the galaxy gas. The galaxy interactions and merging within the group are still enhancing the star formation, from the galaxy disks, which are still rich in dense gas.</div
Training of physical neural networks
No full textInternational audiencePhysical neural networks (PNNs) are a class of neural-like networks that make use of analogue physical systems to perform computations. Although at present confined to small-scale laboratory demonstrations, PNNs could one day transform how artificial intelligence (AI) calculations are performed. Could we train AI models many orders of magnitude larger than present ones? Could we perform model inference locally and privately on edge devices? Research over the past few years has shown that the answer to these questions is probably \"yes, with enough research\". Because PNNs can make use of analogue physical computations more directly, flexibly and opportunistically than traditional computing hardware, they could change what is possible and practical for AI systems. To do this, however, will require notable progress, rethinking both how AI models work and how they are trained-primarily by considering the problems through the constraints of the underlying hardware physics. To train PNNs, backpropagation-based and backpropagation-free approaches are now being explored. These methods have various trade-offs and, so far, no method has been shown to scale to large models with the same performance as the backpropagation algorithm widely used in deep learning today. However, this challenge has been rapidly changing and a diverse ecosystem of training techniques provides clues for how PNNs may one day be used to create both more efficient and larger-scale realizations of present-scale AI models
Gyelmo Murdo : A Textual Journey to a Mountain in the Sino-Tibetan borderlands
No full textInternational audienc
A closer look at the orientation and seasonal rhythms of sheep economies in the early Neolithic of the Adriatic
No full textInternational audienceThe strategic relevance of the Adriatic region in the Neolithization of the central and western Mediterranean is reflected in the prominent presence of the 'maritime stream', associated with the Impressa pottery complex. This stream indicates a remarkable cultural unity between both Adriatic coasts, sustained by continuous interactions, as evidenced by elements of material culture. Economically, both regions share an emphasis on sheep herding and barley cultivation, although they differ in their use of wild resources, reflecting both local adaptations and cultural preferences. However, knowledge about livestock practices remains limited, particularly regarding animal management and exploitation.This study aims to characterize livestock practices in the Adriatic during the early Neolithic, focusing on sheep, the predominant species. Mortality profiles from sites on both coasts will be analyzed to reconstruct the orientation of the production, inferred from herds demographic management. Additionally, pastoral calendars will be investigated at Tinj and Crno Vrilo (Dalmatia) and at Trasano and Rendina (southern Italy) with special attention to the timing of sheep birthing in the annual cycle, in order to reflect potential zootechnical strategies for deseasoning lambing in autumn, as is currently practised in the Mediterranean region.The results are expected to provide a more comprehensive understanding of animal management strategies and the socio-economic organisation of these agropastoral communities, revealing patterns that highlight the role of the Adriatic as a strategic hub in the spread of the Neolithic and the development of early agropastoral economies in the Mediterranean
Unraveling Central Tibet's Sedimentary History: New Insights from the TIBETOP Project
No full textNational audienceReconstructing the formation and evolution of the Himalaya and the Tibetan Plateau, the world's highest mountain range and plateau, is essential for understanding the interplay between geodynamic and surface processes during orogeny, refining Cenozoic paleogeographic and paleoclimatic reconstructions, and investigating biodiversity evolution. In the Tibetan syn-collisional sedimentary basins, fossil records and isotope composition from ancient meteoric water have been widely used to estimate past elevations. However, interpreting these paleoaltimetric data remains contentious, mainly due to poorly constrained chronostratigraphic framework. This results in contrasting topographic growth scenarios, such as in central Tibet, where some authors defend the existence of a high Proto-Tibetan Plateau prior to the India-Asia collision, while others argue for low-elevation valleys persisting into the Neogene, and undergoing major uplift during the Miocene. The Lunpola Basin, located along the Bangong–Nujiang Suture, offers a key setting to resolve this debate. While recent data suggest Middle to Late Eocene elevations of 1000–2000 m, increasing to 3000–4000 m in the Early Miocene, the mechanisms driving basin formation and uplift remain unclear. Because the mechanisms of subsidence that have governed their development are unknown, proposed models in the literature range from rift-related origins to flexural or sag basins. The timing of sedimentation and associated deformation is also poorly constrained, complicating efforts to determine whether uplift of the Tibetan plateau occurred gradually or episodically, and through which geodynamic processes. The ANR-funded TIBETOP project (WP1) addresses these questions by focusing on the Lunpola Basin. A one-month field campaign is scheduled for summer 2025 with three main objectives: (1) refine the chronological framework through magneto-cyclostratigraphy and radiochronology of tuffites and carbonates, (2) reconstruct basins evolution through sedimentological and structural analyses, and (3) expand existing paleoelevations database with new approaches (volcanic glass, triple oxygen analyses). This will provide crucial insights for elucidating the interaction mechanisms between lithospheric dynamics, tectonic uplift, climate change, and biotic evolution in the orogenic plateau. This poster presents the project's initial phase, outlining key observations and working hypotheses