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Cartographier la navigation temporelle dans le cerveau humain
No full textThrough "mental time travel", humans can project themselves in the past or in the future, reliving past events or exploring possible future outcomes (Suddendorf and Corballis, 1997; Tulving, 2002). This ability to navigate mental time requires that events be flexibly mapped on an internal temporal coordinate system - a cognitive map, that may be conceptualized as a "mental timeline" (Arzy et al., 2009). Such cognitive maps have been described in spatial navigation, where a hippocampal-entorhinal circuit enable the representation of the self and the landmarks of the environment, thus allowing for the computation of their spatial relations (Moser et al., 2008; Moser et al., 2015). In this circuit, the organization of neural assemblies by hippocampal theta waves (Bragin et al., 1995; Colgin et al., 2009) enable the computation of temporal distances and allow to mentally revisit past locations or project towards future ones, suggesting that this mechanism may also support mental time travel (Buzsáki and Moser, 2013). The main objective of this PhD project is to explore the role of oscillatory activity and hippocampal structures in self-projection in time. For this, we will use state-of-the-art techniques: (1) Lab psychophysics experiment (2) Non-invasive recordings (EEG/MEG), in order to map out the neural networks involved with high temporal resolution. (3) Virtual reality paradigms (combined with EEG/MEG recordings), to emulate a more complex environment design.Par le voyage mental dans le temps, les êtres humains peuvent se projeter dans le passé ou dans le futur, afin de revivre des moments passés ou d'explorer les futurs possibles (Suddendorf and Corballis, 1997; Tulving, 2002). Cette capacité à naviguer mentalement dans le temps nécessite une cartographie des événements sur un système interne de coordonnées temporelles - une carte cognitive, qui peut être conçue comme une "ligne mentale temporelle" (Arzy et al., 2009). Des cartes cognitives ont déjà été définies dans la navigation spatiale, où un circuit entorhino-hippocampique implémente la représentation du soi et des repères de l'environnement, permettant ainsi la computation de leurs relations spatiales (Moser et al., 2008; Moser et al., 2015). Dans ce circuit, l'organisation des assemblées neurales par les oscillations hippocampiques thêta (Bragin et al., 1995; Colgin et al., 2009) implémente la computation de distances temporelles et permet de revisiter mentalement des lieux passés ou de se projeter vers des lieux futurs, suggérant que ce mécanisme pourrait également implémenter le voyage mental dans le temps (Buzsáki and Moser, 2013). L'objectif principal de ce projet de thèse est l'exploration du rôle de l'activité oscillatoire et des structures hippocampiques dans la projection du soi dans le temps. Pour cela, nous utiliserons des méthodes de l'état de l'art: (1) Expériences psychophysiques en laboratoire. (2) Enregistrements non-invasifs (MEG/EEG), afin de cartographier les réseaux neuronaux impliqués avec une haute précision temporelle. (3) Un paradigme de réalité virtuelle (combiné à des enregistrements MEG/EEG), afin d'implémenter des stimuli plus complexes
A three-phase equation of state for shock-induced phase transitions in tin
No full textInternational audienceThis paper addresses the construction of an equation of state considering three phases of tin for shock-induced phase transitions. First we present general results on such an equation of state which ensure the existence and uniqueness of the problem of maximization on the mixture entropy. Next, a multiphase equation of state under strict thermodynamic equilibrium is obtained using a combination of tabulation and Newton-Raphson iterations. Using this equation of state calibrated with standard static and dynamic experimental data, negative values of the fundamental derivative appear in the (β/γ) mixture zone. A major consequence is the occurrence of composite waves for shock-induced (β → γ) phase transition. We construct the five self-similar reference solutions, using Hugoniot relations and Riemann invariants. Finally, numerical simulations are provided, illustrating these self-similar regimes of the (β → γ) phase transition at thermodynamic equilibrium for increasing piston velocities.Cet article aborde la construction d’une équation d’état prenant en compte trois phases de l’étain pour les transitions de phase induites par choc. Tout d’abord, nous présentons des résultats généraux sur une telle équation d’état, qui garantissent l’existence et l’unicité du problème de maximisation de l’entropie de mélange. Ensuite, une équation d’état multiphase à l’équilibre thermodynamique strict est obtenue en utilisant une méth- ode combinant tabulation et itérations de Newton-Raphson. En utilisant cette équation d’état calibrée sur des données expérimentales statiques et dynamiques de la littérature, des valeurs négatives de la dérivée fondamentale apparaissent dans la zone de mélange (β/γ). Une conséquence importante est l’apparition d’ondes composites pour des tran- sitions de phase (β → γ) sous choc. Nous construisons les cinq solutions auto-similaires de référence, en utilisant les relations de Rankine-Hugoniot et les invariants de Riemann. Enfin, des simulations numériques sont présentées, illustrant ces régimes auto-similaires de la transition de phase (β → γ) à l’équilibre thermodynamique pour des vitesses de piston croissantes
Structural characterization of the ACDC domain from ApiAP2 proteins, a potential molecular target against apicomplexan parasites
No full textInternational audienceThe apicomplexan AP2 (ApiAP2) proteins are the best characterized family of DNA-binding proteins in Plasmodium spp. malaria parasites. Apart from the AP2 DNA-binding domain, there is little sequence similarity between ApiAP2 proteins. However, a conserved AP2-coincident domain mostly at the C-terminus (ACDC domain) is observed in a subset of the ApiAP2 proteins. The structure and function of this domain remain unknown. We report two crystal structures of ACDC domains derived from distinct Plasmodium ApiAP2 proteins, revealing a conserved, unique, noncanonical, four-helix bundle architecture. We used these structures to perform in silico docking calculations against a library of known antimalarial compounds and identified potential small-molecule ligands that bind in a highly conserved hydrophobic pocket that is present in all apicomplexan ACDC domains. These ligands provide a new molecular basis for the future design of ACDC inhibitors
Symmetry of the dissipation of surface acoustic waves by ferromagnetic resonance
No full textInternational audienceWe study the symmetry of the coupling between surface acoustic waves (SAWs) and ferromagnetic resonance in a thin magnetic film of CoFeB deposited on top of a piezoelectric Z-cut LiNbO 3 substrate. We vary the orientation of the applied magnetic field with respect to the wavevector of the SAW. Experiments indicate an unexpected twofold symmetry of the absorption of the SAW energy by the magnetic film. We discuss whether this symmetry can arise from the magnetoelastic torque of the longitudinal strain and the magnetic susceptibility of ferromagnetic resonance. We find that one origin of the twofold symmetry can be the weak in-plane uniaxial anisotropy present within the magnetic film. This phenomenon adds to the previously identified other source of twofold symmetry but shall persist for ultrathin films when the dipolar interactions cease to contribute to the anisotropy of the slope of the spin wave dispersion relation
Ribosome and Transfer RNA Biogenesis
No full textInternational audienceThis chapter focuses on the birth and maturation of ribosomal subunits and transfer RNA (tRNA) molecules in archaea. The ribosomal subunits and tRNA biogenesis processes ensure the production of some of the core molecular components of the translation process. Despite being a distinct domain of life, archaea are often characterized by a mixture of bacterial and eukaryotic features. Ribosome and tRNA biogenesis pathways are not an exception to this rule and as such their studies provide valuable insights into the evolution of these molecular processes and ultimately the evolution of life on Earth. When possible, key conceptual similarities and differences between the biogenesis pathways across the different domains of life will be highlighted. The chapter presents some general information about the diversity, distribution and function of tRNA modifications. It describes, as an example, the synthesis and function of two tRNA modifications specific for archaea
Targeted dual-modality imaging of inflammation using 18 F-radiolabeled iron oxide microparticles
No full textInternational audienceThe ability to noninvasively map vascular inflammation with high spatial and molecular resolution remains a major challenge in biomedical imaging. The integration of both positron emission tomography (PET) and magnetic resonance imaging (MRI) through a dual-modality imaging probe represents a highly attractive approach. Here, we introduce a 18F-labeled hydrophilic sulfotetrazine engineered for rapid and robust bioorthogonal inverse electron demand Diels–Alder (IEDDA) conjugation to BCN (bicyclo[6.1.0]nonyne)-functionalized microsized particles of iron oxides (MPIOs) targeting vascular cell adhesion molecules-1 (VCAM-1) known as key markers of endothelial inflammation. The clickable 18F-reagent exhibits exceptional aqueous solubility and stability, fast second-order kinetics (k2 = 827 M–1·s–1) in the reaction with BCN, and compatibility with automated radiosynthesis platforms. We exploited this tool to generate dual-modality PET/MR 18F-MPIOs@αVCAM-1 by conjugation with MPIOs coated with anti-VCAM-1 antibodies incorporating BCN. Dynamic immuno-PET/MR imaging in a murine model of LPS-induced sepsis revealed strong and specific tracer accumulation in lungs and kidneys in accordance with VCAM-1 overexpression, while high-resolution T2*-MRI confirmed cortical kidney retention with high precision. Thus, the 18F-sulfotetrazine offers a powerful and modular strategy for late-stage functionalization of nanocarriers and sets the stage for the next generation of multimodal probes tailored for real-time tracking of inflammatory pathologies
Understanding health innovation adoption: a realist evaluation of pulse oximeter implementation in primary care for children under 5 in four West African countries
No full textInternational audienceIntroduction Hypoxaemia is an important contributor to child mortality, particularly in low-resource settings where diagnostic tools are scarce. The Améliorer l'Identification des détresses Respiratoires chez l'Enfant project introduced pulse oximeters (POs) into 202 primary healthcare centres (PHCs) in Burkina Faso, Guinea, Mali and Niger, integrating them into the Integrated Management of Childhood Illness guidelines. This initiative aimed to strengthen diagnostic capacities for identifying hypoxaemia and to improve care management for critically ill children under 5. This study examined how healthcare workers (HCWs) adopted POs and explored the contexts and mechanisms influencing their adoption. Methods We conducted a realist evaluation to analyse adoption patterns, focusing on interactions between the Intervention, Contexts, Actors, Mechanisms and Outcomes (ICAMO configurations). Data collection included 299 interviews with HCWs, patients’ families and institutional actors, conducted in 16 selected PHCs, at the institutional level and in district hospitals, complemented by site observations. Analysis was performed using NVivo software, identifying ICAMO configurations as demi-regularities to explain variations in PO use and adoption. Results Training enabled HCWs to recognise the utility of POs, further motivating their use. Support-focused supervision fostered a sense of support, while control-focused approaches sometimes resulted in mechanical use driven by external pressure. In contexts of high workloads and children’s agitation, difficulties in using POs were observed. In settings with limited diagnostic tools, POs increased HCWs’ diagnostic confidence, encouraging adoption and improving decision-making. Observing or knowing the benefits of POs on children’s health provided HCWs with a sense of relief and pride, further reinforcing PO adoption. However, structural barriers and challenges related to institutional adoption may threaten long-term use. Conclusions This study sheds light on the contexts and mechanisms that influence the use and adoption of the PO in PHCs. While widely used by HCWs, addressing challenges related to training, supply chain logistics and referral systems to hospitals is essential to ensure long-term sustainability and improve child health outcomes
Accurate Decomposition of Galaxies with Spiral Arms: Dust Properties and Distribution
No full textInternational audienceWe analyze three nearby spiral galaxies - NGC 1097, NGC 1566, and NGC 3627 - using images from the DustPedia database in seven infrared bands (3.6, 8, 24, 70, 100, 160, and 250 micron). For each image, we perform photometric decomposition and construct a multi-component model, including a detailed representation of the spiral arms. Our results show that the light distribution is well described by an exponential disk and a Sersic bulge when non-axisymmetric components are properly taken into account. We test the predictions of the stationary density wave theory using the derived models in bands, tracing both old stars and recent star formation. Our findings suggest that the spiral arms in all three galaxies are unlikely to originate from stationary density waves. Additionally, we perform spectral energy distribution (SED) modeling using the hierarchical Bayesian code HerBIE, fitting individual components to derive dust properties. We find that spiral arms contain a significant (>10%) fraction of cold dust, with an average temperature of approximately 18-20 K. The estimated fraction of polycyclic aromatic hydrocarbons (PAHs) declines significantly toward the galactic center but remains similar between the arm and interarm regions
Syk activation during FcγR-mediated phagocytosis involves both Syk palmitoylation and desulfenylation
No full textAbstract The non-receptor Spleen tyrosine kinase Syk acts downstream of several receptors of the immune system such as the FcγR. Syk is composed of a kinase domain and two SH2 domains that interact with the bi- phosphorylated ITAMs motifs of the FcγR upon phagocytosis. This results in the activation of Syk by auto- phosphorylation, triggering phosphorylation of several downstream targets in a process that will culminate in F-actin polymerization and phagocytosis of the IgG-opsonized target. We found that Syk is S-acylated upon phagocytosis by macrophages. Palmitoylation is performed on a single Syk-Cys by the protein S-acyl transferase DHHC5 that specifically associates with Syk upon phagocytosis. Syk palmitoylation is required for Syk localization to the phagocytic cup, Syk phosphorylation/activation, Cdc42 recruitment to the cup, F-actin polymerization and phagocytosis. We also observed that another Syk-Cys residue is modified by sulfenylation. Mutation of the sulfenylated Cys that belongs to a redox-motif inactivated the Syk catalytic activity and phagocytosis. We found that Syk desulfenylation occurs during phagocytosis. Molecular dynamics studies indicated that desulfenylation increased the mobility and exposure of a loop within the Syk interdomain B, likely facilitating phosphorylation of key Syk-Tyr residues by upstream effectors such as Src kinases. We thus propose an original updated model for Syk activation during FcγR-mediated phagocytosis that involves both Syk palmitoylation and desulfenylation
Optimizing the potential of KM3NeT in detecting core-collapse supernovae
No full textCore-collapse supernovae mark the end of life of massive stars. However, despite their importance in astrophysics, their underlying mechanisms remain unclear. Neutrinos that emerge from the dense core of the star offer a promising way to study supernova dynamics. A strategy is presented to improve the potential of the KM3NeT neutrino telescope to detect core-collapse supernovae in our Galaxy or the Large Magellanic Cloud by further exploiting the properties of its optical modules equipped with multiple photomultipliers. A supernova burst is expected to produce a sudden hit rate increase in the KM3NeT detectors. New observables have been defined for individual optical modules that exploit the geometry and time distribution of the detected hits, enabling a better discrimination between signal and background signatures. In addition, a thorough investigation of the related systematic uncertainties is presented for the first time. When implemented, this new methodology allowed KM3NeT to probe 46% more Galactic core-collapse supernova candidates than with the previous trigger strategy, reaching the dense Galactic bulge. It is now expected that, once completed, KM3NeT will achieve full Galactic sensitivity to core-collapse supernovae