CEA Grenoble

Calcium ions (Ca2+) orchestrate cellular physiology as a versatile and ubiquitous second messenger, regulating a wide range of intracellular processes, including muscle contraction, secretion, metabolism, cell proliferation, and cell death. Here, we show that optogenetic cytosolic alkalization induced by the outward proton-pumping microbial rhodopsin Arch3 from Halorubrum sodomense triggers extracellular calcium influx into the cytosol of human cells. This elevation in cytosolic Ca2+ is accompanied by a subsequent increase in mitochondrial matrix Ca2+ concentration and depletion of cellular ATP. Together, these findings demonstrate how changes in cytosolic pH can modulate calcium signaling, mitochondrial physiology, and the induction of cell death. These insights are important for fundamental studies of cell physiology and may contribute to the development of improved anticancer therapeutic strategies.

Platinum and its alloys remain the state-of-the-art catalysts for selective nitric oxide production via ammonia oxidation. Yet improving efficiency, selectivity, and stability is a century-old challenge. Operando diffraction techniques are combined with mass spectrometry to investigate structural dynamics of ensemble and single α -Al 2 O 3 -supported Pt crystalline particles under realistic reaction conditions. Only by switching from ensemble averaging methods such as surface X-ray diffraction to single-particle sensitive Bragg coherent diffraction imaging can we identify distinct strain and morphology responses between particle types. Large and elongated particles exhibit annealing-induced misfit strain and a stable morphology during the reaction, while smaller, round, and low-strain particles display surface roughening and defect evolution at 400 °C, coinciding with enhanced NO selectivity. Notably, NH 3 exposure at 600 °C reverses facet strain. These findings highlight the critical role of nanoscale strain and morphology in catalyst performance and demonstrate the power of multi-techniques operando approaches to guide the design of next-generation catalytic materials. • Operando BCDI tracks strain evolution in single Pt nanoparticles during NH 3 oxidation. • Oxygen-rich and ammonia-rich regimes induce distinct defect and strain behaviors. • Structural response varies across particles, highlighting heterogeneity. • Strain in Pt nanoparticles evolve during NH 3 exposure at 600 °C. • Defect formation correlates with catalytic selectivity between NO and N 2 .

Broadband and efficient vertical coupling remains a major challenge in silicon photonics. Conventional grating couplers enable efficient fiber-to-chip coupling but offer a limited bandwidth of around 30 nm, which restricts their use in applications such as wavelength-division multiplexing. In this work, we propose a new fiber-to-chip coupling architecture based on a standard silicon-on-insulator (SOI) platform, composed of a 45° planar reflector and a metalens. We optimized the coupler to operate around 1550 nm. Finite-difference time-domain (FDTD) simulations demonstrate a maximum coupling efficiency of -0.73 dB and a 1 dB bandwidth of 300 nm. The system shows good tolerances to misalignments and process variations, and is compatible with standard microfabrication methods.

RumC1 is a structurally unique bacteriocin with broad-spectrum efficacy, including against multidrug-resistant pathogens, yet acting by an undefined mechanism. By integrating genetics, biochemistry, computational modeling and single-cell fluorescence microscopy, we demonstrate that RumC1 is a distinct cell-wall-targeting toxin. First, all RumC1-resistant mutants isolated through a high-rate, genome-wide mutagenic screening exhibited specific impairments in peptidoglycan homeostasis regulation, pinpointing this pathway as critical for RumC1 activity. Second, RumC1 selectively accumulates within neosynthesized peptidoglycan, leading to cell growth arrest and death in a dose-dependent manner. Third, we characterize the RumIc1 immunity protein of the RumC1 biosynthetic cluster as a peptidase acting at the cell surface to protect the cells by trimming the stem peptide crucial for cell-wall assembly. As such, RumIc1 provides cross-protection against vancomycin, while RumC1 is demonstrated to act differently from this glycopeptide antibiotic. Collectively, these findings establish RumC1 as a toxin targeting a key peptidoglycan intermediate of cell wall maturation.

Abstract Bacillus cereus is a foodborne pathogen able to enter in a viable but non-culturable (VBNC) state, in which cells remain metabolically active but escape detection by conventional culture-based methods used in the food industry. Raman microspectroscopy has emerged as a promising tool for VBNC detection due to its high sensitivity and single-cell resolution. This study evaluated the ability of Raman spectroscopy to discriminate VBNC B. cereus cells from other viability states. Specifically, we investigated (i) whether stressful conditions representative of food-processing environments can induce the VBNC state in B. cereus , and (ii) whether Raman spectral profiles allow differentiation among viability states. Three environmental B. cereus strains were exposed to saline solution and two commonly used food-industry disinfectants for 20 min or 24 h to induce stress. Results demonstrated that such conditions can induce a VBNC state in B. cereus . One strain was further labeled with deuterium, and Raman spectra were collected. Analyses focused on the C–D band and the fingerprint regions. The C–D region enabled discrimination between unstressed and stressed cells, while clustering analysis of the fingerprint region successfully separated unstressed, stressed/injured, VBNC, and dead cells. Mean spectra of each cluster revealed that VBNC cells exhibited marked changes in bands associated with DNA, proteins, cell wall components, and lipid membranes. Overall, this study demonstrates that Raman microspectroscopy, particularly fingerprint region analysis, provides a rapid and non-destructive approach to reliably distinguish VBNC B. cereus cells from other viability states, highlighting its potential for detecting dormant bacteria in food environments.

Highly pathogenic avian influenza viruses (HPAIVs) derive from H5 and H7 low pathogenic avian influenza viruses (LPAIVs). Although insertion of a furin-cleavable multibasic cleavage site (MBCS) in the hemagglutinin gene was identified decades ago as the genetic basis for the LPAIV-to-HPAIV transition, the mechanisms underlying the occurrence of insertion are unknown. Here, we show that transient H5 RNA structures, predicted to trap the influenza virus polymerase on purine-rich sequences, drive nucleotide insertions, providing empirical evidence of RNA structure involvement in MBCS acquisition. Introduction of H5-like sequences and structures into an H6 hemagglutinin resulted in MBCS-yielding insertions. Our results show that nucleotide insertions that underlie H5 HPAIV emergence result from an RNA structure-driven diversity-generating mechanism, which could also occur in other RNA viruses.

Solid–solid phase change materials (SS-PCMs) are attractive candidates for thermal energy storage (TES) owing to their intrinsic shape stability, yet their widespread application remains limited by the lack of design rules linking the molecular structure to phase-transition properties. Here, we present a comprehensive study of layered hybrid chlorometallates, (CnH2n+1NH3)2MCl4 (M = Cu, Mn, Zn; n = 6–16), as tunable SS-PCMs. For that, 15 compounds (M = Cu, Mn, Zn; n = 6, 7, 12, 13, 16) were prepared, and their low-temperature (LT) forms were studied by single-crystal XRD and vibrational spectroscopies. By a multitechnique approach, involving calorimetry, temperature-dependent infrared, and Raman spectroscopies, and combined in a single synchrotron experiment temperature-dependent X-ray absorption spectroscopy (XAS), total scattering/Pair Distribution Function (PDF), and powder XRD (PXRD) analyses, we evidenced the impact of both parameters (M and n) not only on the LT structures but also on the thermal properties and on the high-temperature (HT) structures. Especially, we evidenced that although materials based on octahedrally (here Mn and Cu) and tetrahedrallly (here Zn) coordinated cations share many common features in their LT forms (alternating organic–inorganic layered structures, alkylammonium chains parallel to each other, and supramolecular organic–inorganic interactions of the same nature and strength), their HT phases strongly differ, especially at a medium range distance. This comprehensive study is not only of fundamental interest but will also help to address questions, such as the shaping and mechanical integrity of these SS-PCMs upon thermal cycling that need to be answered prior to their integration into practical devices for next-generation TES.

Bipolar disorder (BD) is a complex mood disorder characterized by recurrent depressive and manic/hypomanic episodes, accompanied by significant cognitive dysfunction and emotional dysregulation. Accurate and timely diagnosis, especially the differentiation between subtypes, remains a challenge due to overlapping symptoms, variable onset times for more specific symptoms (e.g., psychotic features), and the reliance on subjective assessments. This study examines the use of a multimodal approach combining electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to identify patterns of BD emotional dysregulation, aiming to enhance its diagnosis and subtype differentiation. The protocol employed an emotional visual task to evaluate the interference of emotional content on cognitive function. EEG data were collected using a whole-head cap, while fNIRS focused on hemodynamic changes in the frontal cortex. Furthermore, the feasibility of using a potential simplified, portable EEG-fNIRS system was explored by focusing the analysis on frontal regions. The cohort included BD patients [BP] of two main subtypes, and healthy controls [HC]. Behavioral analysis revealed significant performance differences between BP and HC groups. While EEG alone enabled groups' classification, integrating EEG and fNIRS improved accuracy by reducing misclassification rates. Although classification using only frontal EEG regions was slightly less accurate than the full-head cap, fNIRS integration ensured robust results, supporting the feasibility for a potential simplified system. These findings underscore the complementary strengths of EEG and fNIRS in capturing neural and vascular markers of emotional dysregulation in BD and support the development of multimodal diagnostic tools for BD.

Controlling the oxidation state of redox-active ligands during the assembly of Porous Coordination Polymers (PCPs) is a key challenge toward the design of electronically functional frameworks.Herein, we report a galvanostatic solvothermal strategy that enables the in situ electrochemical generation of an open-shell gold(III) bis(dithiolene) ligand during the formation of the network.The reduced tetrabenzoate-functionalized precursor undergoes anodic oxidation under constant current conditions, allowing precise control of the ligand's electronic state during the assembly of the framework.Magnetic measurements reveal regular S = 1/2 antiferromagnetic chains arising from one unpaired electron per Au(III)-dithiolene unit, in agreement with band structure calculations.While the room-temperature conductivity is comparable to that of closed-shell analogues, the charge transport proceeds through a Mott-insulating regime rather than a band-gap-activated mechanism, in agreement with band structure calculations.This electrochemical programming approach provides a general route to open-shell PCPs with electronically correlated ground states.