HAL Portal ESPCI (Ecole Supérieure de Physique et de Chimie Industrielles)
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Onde balistique dans les milieux à désordre corrélé
No full textOndes en milieu hétérogène; GAPSUS - Acoustique Physique, Sous-Marine et Ultra-SonoreNational audienceNous présentons une étude expérimentale et théorique de l'influence des corrélations du désordre sur le comportement de l'onde balistique voyageant à travers un milieu hétérogène diffusant. Les échantillons considérés consistent en des assemblées 2D de diffuseurs cylindriques en cuivre (de diamètre millimétrique) répartis de façon aléatoire et immergés dans l'eau. Pour une émission ultrasonore large bande dans la gamme du MHz, nous avons comparé la transmission balistique à travers un milieu dilué, bien décrite dans l'approximation de diffusion indépendante (ISA), et à travers un empilement compact. Par rapport aux expériences qui ont déjà pu être menées dans le passé sur des milieux du même type, l'originalité de notre étude réside dans la mise en évidence d'un très fort effet de dispersion de l'onde transmise à forte concentration en diffuseurs: celle-ci se compose alors d'une onde balistique cohérente basse fréquence suivie d'une onde multiplement diffusée plus haute fréquence. Une étude numérique menée en parallèle indique que cet effet ne nécessite pas la mise en contact des diffuseurs mais apparaît pour des concentrations surfaciques élevées, typiquement de l'ordre de 50% (Q. Ma et al., Acta Acustica, Chinese version, 46, 1178, 2021), pour lesquelles les corrélations du désordre doivent être prises en compte. Cette étude a été motivée par des travaux dans lesquels un comportement du même type avait été mis en évidence dans des milieux (3D) granulaires secs sous contrainte (Jia et al., Phys. Rev. Lett., 82, 1863, 1999) et, plus récemment, dans des suspensions denses de particules
La signalisation calcique nucléaire dans les neurones exprimant le récepteur D1 du noyau accumbens régule les adaptations moléculaires, cellulaires et comportementales à la cocaïne
No full textInternational audienceBACKGROUND: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens [NAc]). Notably, activation of the ERK (extracellular signalregulated kinase) pathway in the striatum is known to trigger a transcriptional program shaping long-term responses to cocaine. Nuclear calcium signaling has also been shown to control multiple forms of transcription-dependent neuroadaptations, but the dynamics and roles of striatal nuclear calcium signaling in preclinical models of addiction remain unknown. METHODS: A genetically encoded cell type-specific nuclear calcium probe has been developed to monitor calcium dynamics in the nuclei of striatal neurons, including in freely moving mice. A cell type-specific inhibitor of nuclear calcium signaling combined with 3-dimensional imaging of neuronal morphology, immunostaining, and behavior was used to disentangle the roles of nuclear calcium in NAc medium spiny neurons (MSNs) expressing the dopamine D 1 receptor (D1R) or D 2 receptor (D2R) on cocaine-evoked responses. RESULTS: The D1R-mediated potentiation of calcium influx through glutamate NMDA receptors, which shapes cocaine effects, also drives nuclear calcium transients. Fiber photometry revealed that cocaine-treated mice showed a sustained nuclear calcium increase in NAc D1R-MSNs. Disrupting nuclear calcium in D1R-MSNs, but not D2R-MSNs, blocked cocaine-evoked morphological changes of MSNs and gene expression and blunted cocaine's rewarding effects. CONCLUSIONS: Our study unravels the dynamics and roles of cocaine-induced nuclear calcium signaling increases in D1R-MSNs on molecular, cellular, and behavioral adaptations to cocaine and represents a significant breakthrough because it could contribute to the development of innovative strategies with therapeutic potential to alleviate addiction symptoms
Perinatal Maturation of Drug Transporters and Claudin‐5 at the Blood–Brain Barrier
No full textInternational audienceABSTRACT Aim Cerebral capillary endothelial cells (EC) form the blood–brain barrier (BBB), which regulates molecular exchange between the blood and the brain. Understanding their function during brain development is essential for optimizing treatments in neonates, children, as well as pregnant and breastfeeding women. Methods P‐glycoprotein (P‐gp/ABCB1) expression during brain development was assessed by immunohistochemistry in human cortical samples. In mice, postnatal brain microvessels were analyzed using qPCR and Western Blot, and BBB function was evaluated in vivo using [ 14 C]sucrose to assess barrier integrity, and [ 3 H]verapamil or [ 3 H]rosuvastatin to assess transport activity. Results In humans, P‐gp reached mature levels in the early postnatal period. In mice, BBB integrity was established by postnatal day 5 (P5), but the expression of claudin‐5, P‐gp, and Oatp1a4 increased until P30. Brain transport of verapamil and rosuvastatin significantly decreased between P15 and P30, indicating enhanced efflux capacity. Conclusions Although BBB integrity is established at birth, BBB continues maturing throughout the postnatal period, with a predominant efflux transport. Our findings underscore the critical role of P‐gp in the acquisition of BBB gatekeeper properties. The immature BBB may result in a higher brain susceptibility to P‐gp substrates in preterm infants
Dynamical phase transitions in the nonreciprocal Ising model
No full textInternational audienceNonreciprocal interactions in many-body systems lead to time-dependent states, commonly observed in biological, chemical, and ecological systems. The stability of these states in the thermodynamic limit and the critical behavior of the phase transition from static to time-dependent states are not yet fully understood. To address these questions, we study a minimalistic system endowed with nonreciprocal interactions: an Ising model with two spin species having opposing goals. The mean-field equation predicts three stable phases: disorder, static order, and a time-dependent swap phase. Large scale numerical simulations support the following: (i) in 2D, the swap phase is destabilized by defects; (ii) in 3D, the swap phase is stable, and has the properties of a time crystal; (iii) the transition from disorder to swap in 3D is characterized by the critical exponents of the 3D XY model, and corresponds to the breaking of a continuous symmetry, time translation invariance; (iv) when the two species have fully anti-symmetric couplings, the static-order phase is unstable in any finite dimension due to droplet growth; (v) in the general case of asymmetric couplings, static order can be restored by a droplet-capture mechanism preventing the droplets from growing indefinitely. We provide details on the full phase diagram which includes first-and second-order-like phase transitions and study how the system coarsens into swap and static-order states
Use of rescue noninvasive ventilation for post-extubation respiratory failure
No full textInternational audienceBackground: Robust evidence supports the use of preemptive non-invasive ventilation (NIV) after extubation in selected high-risk patient cohorts. In contrast, current guidelines discourage the use of NIV as a rescue therapy for respiratory failure that develops later after extubation, based on earlier studies indicating a potential increase in hospital mortality due to delayed reintubation. Nonetheless, NIV continues to be employed in this setting. We conducted a post-hoc analysis of a randomized trial to assess the clinical outcomes of rescue NIV for post-extubation respiratory failure.Methods: In this post-hoc analysis of a randomized trial comparing high-flow with Venturi mask oxygen in hypoxemic patients after extubation, we included those who developed post-extubation respiratory failure according to prespecified criteria; patients who received rescue NIV per physician’s decision were compared to those who received direct re-intubation. Criteria for re-intubation during NIV were prespecified. Odds ratio after inverse probability of treatment weighting and posterior probabilities by Bayesian regression are reported.Results: Among 494 extubated patients, 147 developed respiratory failure while receiving oxygen therapy, occurring at a median of 37 h [IQR 13–85] after extubation: 83 (57%) were treated with rescue NIV and 64 (43%) received immediate re-intubation. The rate of NIV failure was 58%, without differences between patients with hypoxemic respiratory failure and those with hypercapnia and/or respiratory distress (60% vs. 56%, p = 0.82). In the weighted cohort, the use of rescue NIV, compared to direct re-intubation, was associated with lower intensive care unit mortality (adjusted odds ratio = 0.31 [95%CI: 0.12–0.82], p = 0.019) and similar hospital mortality (adjusted odds ratio = 1.01 [95%CI: 0.43–2.33], p = 0.99). The posterior probability that NIV reduced intensive care unit mortality was > 90% across all priors. The posterior probability that NIV did not increase hospital mortality was 44% under a noninformative prior, 47% under a skeptical prior, and 39% under a pessimistic prior.Conclusion: Rescue NIV for post-extubation respiratory failure is associated with high failure rates; however, when applied with well-defined criteria for reintubation, it does not appear to be clearly associated with increases in hospital mortality. A randomized trial to re-evaluate the efficacy of rescue NIV for post-extubation respiratory failure is warranted.Clinical trial registration: Registered at clinicaltrials.gov (NCT02107183) on April 8th, 2014
Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors
No full textInternational audienceNicotine activates ventral tegmental area (VTA) dopaminergic (DA) neurons projecting to the nucleus accumbens (NAc) to drive its reinforcing effects. Simultaneously, nicotine inhibits those projecting to the amygdala (Amg) to mediate anxiety-like behavior through a process that remains unknown. Here, we show that in male mice, NAc- and Amg-projecting DA neurons respond with similar polarities to ethanol and nicotine, suggesting a shared network-based mechanism underlying the inhibitory effect of these otherwise pharmacologically-distinct drugs. Selective activation of NAc-projecting DA neurons, using genetic or optogenetic strategies, produced inhibition of Amg-projecting DA neurons, through a GABAergic feedback loop. Furthermore, optogenetically silencing this feedback loop prevented nicotine from inducing both inhibition of DA neurons and anxiety-like behavior. Therefore, nicotine-induced inhibition of the VTA-Amg DA pathway results from a VTA-NAc inhibitory feedback loop, mediating anxiety-like behavior
French national protocol for diagnosis and management of epidermal necrolysis in adults (Stevens-Johnson syndrome and toxic epidermal necrolysis)
No full textTransport of spherical microparticles in a 3D vortex flow
No full textParticles are common in biological and environmental flows and are widely used in industrial and pharmaceutical applications. Their motion and flow dynamics are strongly affected by interactions with the surrounding flow structure. While particle-flow interactions have been extensively studied in low Reynolds number (Re) flows as well as in fully developed turbulence, the transport mechanisms of these particles in intermediate flow regimes remain less explored. Here, we investigate the response of neutrally buoyant spherical particles to a single vortex flow field. Using a microfluidic crossslot geometry, we generate a well-characterized, stationary, three-dimensional streamwise vortex at moderate Re (∼ 50). Our experimental results, supported by numerical simulations, show that with increasing particle diameter, they are progressively excluded from the vortex core. Initially, small particles follow a Burgers vortex-like self-similar motion, but for larger particle diameters, deviations from this trend emerge due to fluid inertia and finite-size effects. These findings enhance our understanding of particle dynamics in vortical flows and have implications for microfluidic applications involving particle sorting and separation
Dopaminergic mechanisms of dynamical social specialization in mouse microsocieties
No full textSocial organization and division of labor are fundamental to animal societies, but how do these structures emerge from individual interactions, and what role does neuromodulation play in shaping them? Using behavioral tracking in a semi-natural environment, neural recordings, and computational models integrating reinforcement and social learning, we show that groups of three isogenic mice spontaneously develop specialized roles while solving a foraging task requiring individual decisions under social constraints. Moreover, these roles are shaped by dopaminergic activity in the ventral tegmental area. Strikingly, despite minor sex-differences in behavior when mice were tested alone, male triads formed stable worker-scrounger relationships driven by competition, whereas female triads adopted uniform, cooperative strategies. Model analysis revealed how intra- and inter-sex parameter differences in resource exploitation, combined with contingent and dynamic social interactions, drive behavioral specialization and labor division. Most notably, it highlighted how contingency, amplified by competition, magnifies individual differences and shapes social profiles. The plastic, adaptive nature of social organization within triads was confirmed by manipulating dopaminergic cell activity, which reshaped social roles and altered group structure. Our findings support a feedback loop where social context shapes neural states, which in turn reinforce behavioral specialization and stabilize social structures
Influence of a Two-Fold Ligation Pattern on Iron-Mediated Aryl-Heteroaryl Cross-Electrophile Couplings
No full textInternational audienceAn aryl-heteroaryl Cross-Electrophile Coupling (XEC) relying on the use of a single, well-defined iron catalyst is disclosed, involving magnesium as an electron source as well as heteroaryl chlorides and aryl iodides or bromides as coupling partners. A two-fold coordination pattern featuring a π-acceptor, redox-active (N,N) ligand along with a σ-donating phosphine ensures both the two-electron reduction of the starting iron(II) precursor to enter the cycle, as well as the access to stable organoiron(II) resting states inhibiting the reductive decomposition of the catalyst