French National Centre for Scientific Research

Membrane contact sites (MCS) between intracellular organelles regulate lipid exchange, organelles dynamics and spatial organization of signaling pathways, yet their contribution to regulated exocytosis remains poorly understood. Here, we investigated the role of endoplasmic reticulum (ER) MCS in calcium-regulated exocytosis using primary bovine chromaffin cells. Combining electron microscopy on plasma membrane (PM) sheets with immunogold labeling, we identified ER structures contacting docked secretory granules and classified three types of MCS: ER-PM, ER-granule and tripartite ER-PM-granule contacts. These contacts are enriched at exocytic sites and contain Orai1 and STIM1, both known for mediating store-operated calcium release. Functional perturbation of the Orai/STIM pathway revealed that constitutive STIM activation or pharmacological inhibition of Orai1 reduced the number of exocytotic events, slowed catecholamine release and disrupted actin organization at granule docking sites. Together, our findings revealed a previously unrecognized role for ER MCS in organizing exocytic sites and controlling secretion efficiency in neuroendocrine cells.

https://doi.org/10.64628/AAK.vm3vjgjcw

• A time-domain Rankine panel method for seakeeping with forward speed is presented. • The code allows the use of multi-resolution meshes to improve efficiency. • An incident impulse wave is used to calculate RAOs. • Results are analyzed in calm water, head waves and following waves. A time-domain potential-flow solver is developed to study the linearized ship-wave interaction problem with forward speed. A Rankine panel method is implemented to model both a hull advancing in calm water and in waves. The former case is important in evaluating the wave-making resistance of hulls while the latter gives the hydrodynamic loads and motion responses for ships interacting with ocean waves. A constant panel method with an indirect approach is adopted to obtain a robust and efficient simulation tool. The problem is formulated such that no connectivity information on the mesh is necessary, allowing the use of multi-resolution meshes that reduce the computational costs in a simple and efficient way. The calm water problem is validated on a Wigley hull. A convergence analysis is conducted, investigating both the wave resistance and the wave profile. For the unsteady seakeeping problem, tests with an impulse wave are implemented to reduce simulation times. The radiation and diffraction loads, and the motion responses for the RIOS bulk carrier in head waves are presented. In addition, the S175 containership is studied in head and in following seas, showing the method is capable of predicting the hull response in both sea conditions with forward speed. A final test in irregular waves demonstrates the ability of the solver in simulating realistic sea conditions.

Abstract Modeling sea ice microwave emissivities at large scales presents challenges, due to complex interactions between the microwave signal and the sea ice environment. For the preparation of the Copernicus Imaging Microwave Radiometer mission (CIMR) that focusses on the monitoring of polar regions, a pragmatic parameterization of the sea ice emissivity over the Arctic in winter is proposed, providing consistent emissivity parameterizations between 1.4 and 36 GHz, for both orthogonal polarizations. Satellite‐derived microwave emissivities are calculated from the Advanced Microwave Scanning Radiometer 2, Soil Moisture Active Passive, and Soil Moisture Ocean Salinity observations, subtracting the atmospheric contributions and the surface temperature modulation using ERA5 meteorological reanalysis. The resulting Arctic sea ice emissivities are analyzed, alongside sea ice geophysical parameters from neXtSIM model outputs and ERA5, to identify the variables for the emissivity parameterization. Sea Ice Thickness emerges as a crucial factor, particularly at 18 and 36 GHz. A training database of coincident satellite‐derived emissivities and geophysical parameters is set up, to develop a Neural Network parameterization of the emissivities based on the geophysical parameters. This pragmatic methodology establishes a direct link between calculated emissivities and physical sea ice properties, eliminating the need for a priori assumptions. Promising emissivity results are obtained, with Root Mean Square Error below 0.03 for most channels, and reaching 0.04 at 36 GHz. Part of the error is expected to come from uncertainties in the input geophysical parameters. The emissivity frequency dependence is checked, and the emissivity angular variation of the 1.4 GHz is calculated from SMOS‐derived emissivities.

Targeting the chromatin-modifying activities of the SUV4-20H enzyme family offers a promising epigenetic strategy to enhance the potency of the topoisomerase-2 poison etoposide in prostate cancer therapy.

Galactic weak-scale Dark Matter (DM) particles annihilating into lepton-rich channels not only produce gamma-rays via prompt radiation but also generate abundant energetic electrons and positrons, which subsequently emit through bremsstrahlung or inverse Compton scattering (collectively called “secondary-radiation photons”). While the prompt gamma-rays concentrate at high-energy, the secondary emission falls in the MeV range, which a number of upcoming experiments (AMEGO, E-ASTROGAM, MAST…) will probe. We investigate the sensitivity of these future telescopes for weak-scale DM, focusing for definiteness on observations of the galactic center. We find that they have the potential of probing a wide region of the DM parameter space which is currently unconstrained. Namely, in rather optimistic configurations, future MeV telescopes could probe thermally-produced DM with a mass up to the TeV range, or GeV DM with an annihilation cross section 2 to 3 orders of magnitude smaller than the current bounds, precisely thanks to the significant leverage provided by their sensitivity to secondary emissions. We comment on astrophysical and methodological uncertainties, and compare with the reach of high-energy gamma ray experiments.

By using the Bogoliubov perturbation theory we describe the self-bound ground state and excited breathing states of NN two-dimensional bosons with zero-range attractive interactions. Our results for the ground state energy B_NBN and size R_NRN improve previously known large-NN asymptotes and we better understand the crossover to the few-body regime. The breathing oscillations, absent at the mean-field level, result from the quantum-mechanical breaking of the mean-field scale symmetry. The breathing-mode frequency scales as \Omega\propto |B_N|/\sqrt{N}Ω∝|BN|/N at large NN.