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1. Structures of active Hantaan virus polymerase uncover the mechanisms of Hantaviridae genome replication

Author: Quentin Durieux Trouilleton, Sergio Barata-García, Benoît Arragain, Juan Reguera, Hélène Malet, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Architecture et fonction des macromolécules biologiques (AFMB), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Hantaviruses are causing life-threatening zoonotic infections in humans. Their tripartite negative-stranded RNA genome is replicated by the multi-functional viral RNA-dependent RNA-polymerase. Here we describe the structure of the Hantaan virus polymerase core and establish conditions for in vitro replication activity. The apo structure adopts an inactive conformation that involves substantial folding rearrangement of polymerase motifs. Binding of the 5′ viral RNA promoter triggers Hantaan virus polymerase reorganization and activation. It induces the recruitment of the 3′ viral RNA towards the polymerase active site for prime-and-realign initiation. The elongation structure reveals the formation of a template/product duplex in the active site cavity concomitant with polymerase core widening and the opening of a 3′ viral RNA secondary binding site. Altogether, these elements reveal the molecular specificities of Hantaviridae polymerase structure and uncover the mechanisms underlying replication. They provide a solid framework for future development of antivirals against this group of emerging pathogens.
Published: 2023

2. DNA-binding mechanism and evolution of replication protein A

Author: Clément Madru, Markel Martínez-Carranza, Sébastien Laurent, Alessandra C. Alberti, Maelenn Chevreuil, Bertrand Raynal, Ahmed Haouz, Rémy A. Le Meur, Marc Delarue, Ghislaine Henneke, Didier Flament, Mart Krupovic, Pierre Legrand, Ludovic Sauguet, Architecture et Dynamique des Macromolécules Biologiques - Architecture and Dynamics of Biological Macromolecules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biologie et Ecologie des Ecosystèmes Marins Profonds (BEEP), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Cristallographie (Plateforme) - Crystallography (Platform), Plateforme Technologique de RMN Biologique et HDX-MS - Biological NMR and HDX-MS Technological Platform, Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), We gratefully acknowledge the financial support of ANR (Grants ARCHAPOL and ARCHAPRIM). C.M. was funded by a postdoctoral Pasteur-Roux-Cantarini fellowship. M.M.C. was funded by a postdoctoral FRM fellowship (Fondation pour la Recherche Médicale)., ANR-17-CE11-0005,ARCHAPOL,Spécificités structurales et potentiel biotechnologique de la PolD, une ADN polymérase atypique d'archée(2017), and ANR-20-CE11-0003,ARCHAPRIM,L'ADN primase, le couteau Suisse des Archées: Etude de biologie intégrative(2020)
Subjects: MESH: DNA Repair, MESH: DNA, Single-Stranded, Multidisciplinary, [SDV]Life Sciences [q-bio], MESH: DNA, MESH: Protein Binding, General Physics and Astronomy, MESH: DNA Replication, General Chemistry, MESH: Replication Protein A, General Biochemistry, Genetics and Molecular Biology
Abstract: Replication Protein A (RPA) is a heterotrimeric single stranded DNA-binding protein with essential roles in DNA replication, recombination and repair. Little is known about the structure of RPA in Archaea, the third domain of life. By using an integrative structural, biochemical and biophysical approach, we extensively characterize RPA from Pyrococcus abyssi in the presence and absence of DNA. The obtained X-ray and cryo-EM structures reveal that the trimerization core and interactions promoting RPA clustering on ssDNA are shared between archaea and eukaryotes. However, we also identified a helical domain named AROD (Acidic Rpa1 OB-binding Domain), and showed that, in Archaea, RPA forms an unanticipated tetrameric supercomplex in the absence of DNA. The four RPA molecules clustered within the tetramer could efficiently coat and protect stretches of ssDNA created by the advancing replisome. Finally, our results provide insights into the evolution of this primordial replication factor in eukaryotes.
Published: 2023

3. Advancing research on compound weather and climate events via large ensemble model simulations

Author: Emanuele Bevacqua, Laura Suarez-Gutierrez, Aglaé Jézéquel, Flavio Lehner, Mathieu Vrac, Pascal Yiou, Jakob Zscheischler, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Max Planck Institute for Meteorology (MPI-M), Max-Planck-Gesellschaft, Institute for Atmospheric and Climate Science [Zürich] (IAC), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cornell University [New York], Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Extrèmes : Statistiques, Impacts et Régionalisation (ESTIMR), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Multidisciplinary, [SDU]Sciences of the Universe [physics], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Societally relevant weather impacts typically result from compound events, which are rare combinations of weather and climate drivers. Focussing on four event types arising from different combinations of climate variables across space and time, here we illustrate that robust analyses of compound events - such as frequency and uncertainty analysis under present-day and future conditions, event attribution to climate change, and exploration of low-probability-high-impact events - require data with very large sample size. In particular, the required sample is much larger than that needed for analyses of univariate extremes. We demonstrate that Single Model Initial-condition Large Ensemble (SMILE) simulations from multiple climate models, which provide hundreds to thousands of years of weather conditions, are crucial for advancing our assessments of compound events and constructing robust model projections. Combining SMILEs with an improved physical understanding of compound events will ultimately provide practitioners and stakeholders with the best available information on climate risks., Nature Communications, 14 (1), ISSN:2041-1723
Published: 2023

4. Legionella para-effectors target chromatin and promote bacterial replication

Author: Daniel Schator, Sonia Mondino, Jérémy Berthelet, Cristina Di Silvestre, Mathilde Ben Assaya, Christophe Rusniok, Fernando Rodrigues-Lima, Annemarie Wehenkel, Carmen Buchrieser, Monica Rolando, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Génomique des Microorganismes Pathogènes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Toxines bactériennes dans la relation hôtes-pathogènes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA) that methylates K14 of histone H3 (H3K14me3) to counteract host immune responses. However, it is not known how L. pneumophila infection catalyses H3K14 methylation as this residue is usually acetylated. Here we show that L. pneumophila secretes a eukaryotic-like histone deacetylase (LphD) that specifically targets H3K14ac and works in synergy with RomA. Both effectors target host chromatin and bind the HBO1 histone acetyltransferase complex that acetylates H3K14. Full activity of RomA is dependent on the presence of LphD as H3K14 methylation levels are significantly decreased in a ∆lphD mutant. The dependency of these two chromatin-modifying effectors on each other is further substantiated by mutational and virulence assays revealing that the presence of only one of these two effectors impairs intracellular replication, while a double knockout (∆lphD∆romA) can restore intracellular replication. Uniquely, we present evidence for “para-effectors”, an effector pair, that actively and coordinately modify host histones to hijack the host response. The identification of epigenetic marks modulated by pathogens has the potential to lead to the development of innovative therapeutic strategies to counteract bacterial infection and strengthening host defences.
Published: 2023

5. The Fe-FeSi phase diagram at Mercury’s core conditions

Author: E. Edmund, G. Morard, M. A. Baron, A. Rivoldini, S. Yokoo, S. Boccato, K. Hirose, A. Pakhomova, D. Antonangeli, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for High Pressure Science & Technology Advanced Research (HPSTAR), Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), Royal Observatory of Belgium [Brussels] (ROB), The University of Tokyo (UTokyo), Earth-Life Science Institute [Tokyo] (ELSI), Tokyo Institute of Technology [Tokyo] (TITECH), and Deutsches Elektronen-Synchrotron [Hamburg] (DESY)
Subjects: [PHYS]Physics [physics], Multidisciplinary, Science, technology, industry, and agriculture, General Physics and Astronomy, General Chemistry, Article, General Biochemistry, Genetics and Molecular Biology, [SDU]Sciences of the Universe [physics], Core processes, Inner planets, Physics::Space Physics, Structure of solids and liquids, Astrophysics::Solar and Stellar Astrophysics, lipids (amino acids, peptides, and proteins), ddc:500, Astrophysics::Earth and Planetary Astrophysics
Abstract: Nature Communications 13(1), 387 (2022). doi:10.1038/s41467-022-27991-9, Mercury��s metallic core is expected to have formed under highly reducing conditions, resulting in the presence of significant quantities of silicon alloyed to iron. Here we present the phase diagram of the Fe-FeSi system, reconstructed from in situ X-ray diffraction measurements at pressure and temperature conditions spanning over those expected for Mercury��s core, and ex situ chemical analysis of recovered samples. Under high pressure, we do not observe a miscibility gap between the cubic fcc and B2 structures, but rather the formation of a re-entrant bcc phase at temperatures close to melting. Upon melting, the investigated alloys are observed to evolve towards two distinct Fe-rich and Fe-poor liquid compositions at pressures below 35-38 GPa. The evolution of the phase diagram with pressure and temperature prescribes a range of possible core crystallization regimes, with strong dependence on the Si abundance of the core., Published by Nature Publishing Group UK, [London]
Published: 2022

6. A bimodal distribution of haze in Pluto’s atmosphere

Author: Siteng Fan, Peter Gao, Xi Zhang, Danica J. Adams, Nicholas W. Kutsop, Carver J. Bierson, Chao Liu, Jiani Yang, Leslie A. Young, Andrew F. Cheng, Yuk L. Yung, Robotique médicale et mécanismes parallèles (DEXTER), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Carnegie Institution for Science, Laboratoire de Génie Civil, Diagnostic et Durabilité (GC2D), Institut Matériaux Procédés Environnement Ouvrages (IMPEO), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), University of California [Santa Cruz] (UC Santa Cruz), University of California (UC), Cornell University [New York], California Institute of Technology (CALTECH), Southwest Research Institute [Boulder] (SwRI), and Johns Hopkins University (JHU)
Subjects: Earth and Planetary Astrophysics (astro-ph.EP), Atmospheric dynamics, Atmospheric chemistry, Multidisciplinary, [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], Science, FOS: Physical sciences, General Physics and Astronomy, General Chemistry, Article, General Biochemistry, Genetics and Molecular Biology, Asteroids, comets and Kuiper belt, Astrophysics - Earth and Planetary Astrophysics
Abstract: Pluto, Titan, and Triton make up a unique class of solar system bodies, with icy surfaces and chemically reducing atmospheres rich in organic photochemistry and haze formation. Hazes play important roles in these atmospheres, with physical and chemical processes highly dependent on particle sizes, but the haze size distribution in reducing atmospheres is currently poorly understood. Here we report observational evidence that Pluto’s haze particles are bimodally distributed, which successfully reproduces the full phase scattering observations from New Horizons. Combined with previous simulations of Titan’s haze, this result suggests that haze particles in reducing atmospheres undergo rapid shape change near pressure levels ~0.5 Pa and favors a photochemical rather than a dynamical origin for the formation of Titan’s detached haze. It also demonstrates that both oxidizing and reducing atmospheres can produce multi-modal hazes, and encourages reanalysis of observations of hazes on Titan and Triton., Pluto’s haze is revealed to have two types of particles: small spherical organic haze particles and micron-size fluffy aggregates. The persistence of these two populations has important implications for haze formation and properties on icy worlds.
Published: 2022

7. TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV

Author: Matkovic, R., Morel, M., Lanciano, S., Larrous, P., Martin, B., Bejjani, F., Vauthier, V., Hansen, M.M.K., Emiliani, S., Cristofari, G., Gallois-Montbrun, S., Margottin-Goguet, F., Emiliani, Stephane, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Radboud University [Nijmegen]
Subjects: RNA Stability, Science, Gene Expression, HIV Infections, Epigenetic Repression, Article, Histones, Proviruses, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Schizosaccharomyces, Humans, HIV Long Terminal Repeat, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Retrovirus, Nuclear Proteins, Gene silencing, Histone-Lysine N-Methyltransferase, Chromatin Assembly and Disassembly, Phosphoproteins, HIV-2, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA Polymerase II, Restriction factors, Biophysical Chemistry, HeLa Cells, Transcription Factors
Abstract: The Human Silencing Hub (HUSH) complex constituted of TASOR, MPP8 and Periphilin recruits the histone methyl-transferase SETDB1 to spread H3K9me3 repressive marks across genes and transgenes in an integration site-dependent manner. The deposition of these repressive marks leads to heterochromatin formation and inhibits gene expression, but the underlying mechanism is not fully understood. Here, we show that TASOR silencing or HIV-2 Vpx expression, which induces TASOR degradation, increases the accumulation of transcripts derived from the HIV-1 LTR promoter at a post-transcriptional level. Furthermore, using a yeast 2-hybrid screen, we identify new TASOR partners involved in RNA metabolism including the RNA deadenylase CCR4-NOT complex scaffold CNOT1. TASOR and CNOT1 synergistically repress HIV expression from its LTR. Similar to the RNA-induced transcriptional silencing complex found in fission yeast, we show that TASOR interacts with the RNA exosome and RNA Polymerase II, predominantly under its elongating state. Finally, we show that TASOR facilitates the association of RNA degradation proteins with RNA polymerase II and is detected at transcriptional centers. Altogether, we propose that HUSH operates at the transcriptional and post-transcriptional levels to repress HIV proviral expression., The human silencing hub (HUSH) complex, which includes TASOR, deposits repressive marks on HIV proviruses, resulting in gene repression. Here, Matkovic et al. show that TASOR interacts with RNA Polymerase II, predominantly under its elongating state, and RNA degradation proteins to repress HIV provirus expression.
Published: 2022

8. Cornering the universal shape of fluctuations

Author: Benoit Estienne, Jean-Marie Stéphan, William Witczak-Krempa, HEP, INSPIRE, Laboratoire de Physique Théorique et Hautes Energies (LPTHE), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: High Energy Physics - Theory, Quantum information, dimension: 3, metal, [PHYS.PHYS.PHYS-GEN-PH] Physics [physics]/Physics [physics]/General Physics [physics.gen-ph], Science, Quantum Hall, FOS: Physical sciences, General Physics and Astronomy, 01 natural sciences, Article, General Biochemistry, Genetics and Molecular Biology, 010305 fluids & plasmas, Condensed Matter - Strongly Correlated Electrons, Mesoscale and Nanoscale Physics (cond-mat.mes-hall), 0103 physical sciences, Topological insulators, structure, 010306 general physics, Condensed Matter - Statistical Mechanics, Multidisciplinary, Strongly Correlated Electrons (cond-mat.str-el), Statistical Mechanics (cond-mat.stat-mech), Condensed Matter - Mesoscale and Nanoscale Physics, [PHYS.HTHE]Physics [physics]/High Energy Physics - Theory [hep-th], scaling, General Chemistry, Hall effect: fractional, [PHYS.PHYS.PHYS-GEN-PH]Physics [physics]/Physics [physics]/General Physics [physics.gen-ph], geometry: fluctuation, Phase transitions and critical phenomena, High Energy Physics - Theory (hep-th), Quantum Gases (cond-mat.quant-gas), correlation, [PHYS.HTHE] Physics [physics]/High Energy Physics - Theory [hep-th], Condensed Matter - Quantum Gases
Abstract: Understanding the fluctuations of observables is one of the main goals in science, be it theoretical or experimental, quantum or classical. We investigate such fluctuations in a subregion of the full system, focusing on geometries with sharp corners. We report that the angle dependence is super-universal: up to a numerical prefactor, this function does not depend on anything, provided the system under study is uniform, isotropic, and correlations do not decay too slowly. The prefactor contains important physical information: we show in particular that it gives access to the long-wavelength limit of the structure factor. We exemplify our findings with fractional quantum Hall states, topological insulators, scale invariant quantum critical theories, and metals. We suggest experimental tests, and anticipate that our findings can be generalized to other spatial dimensions or geometries. In addition, we highlight the similarities of the fluctuation shape dependence with findings relating to quantum entanglement measures., Fluctuations, both quantum and classical, contain important information about the underlying system. Here, the authors show that for measurements on a subregion with a sharp corner, fluctuations have the same shape dependence for a large variety of systems.
Published: 2022

9. Premature commitment to uncertain decisions during human NMDA receptor hypofunction

Author: Alexandre Salvador, Luc H. Arnal, Fabien Vinckier, Philippe Domenech, Raphaël Gaillard, Valentin Wyart, Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), GHU Paris Psychiatrie et Neurosciences, Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Institut de l'Audition [Paris] (IDA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Motivation, cerveau et comportement = Motivation, Brain and Behavior [ICM Paris] (MBB), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neurophysiologie des comportements répétitifs [ICM Paris], Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work was supported by a starting grant from the European Research Council (ERC-StG-759341) awarded to V.W., a junior researcher grant from the French National Research Agency (ANR-14-CE13-0028-01) awarded to V.W., a young investigator award from the Fyssen Foundation to V.W., a donation from the Schizo-oui association to R.G., and a starting grant from the Institut de Psychiatrie et de Neurosciences de Paris awarded to R.G. A.S. was funded by a doctoral fellowship from the Fondation pour la Recherche Médicale., ANR-14-CE13-0028,SUB-DECISION,Sous-optimalité de la prise de décision humaine : redéfinir les modèles du choix en termes en contraintes neurobiologiques(2014), European Project: 759341,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),ERC-2017-STG,OPTIMIZERR(2018), Gestionnaire, Hal Sorbonne Université, Appel à projets générique - Sous-optimalité de la prise de décision humaine : redéfinir les modèles du choix en termes en contraintes neurobiologiques - - SUB-DECISION2014 - ANR-14-CE13-0028 - Appel à projets générique - VALID, and Errors as cost-optimizing decisions? Redefining the origin and nature of human decision errors in light of associated neural computations - OPTIMIZERR - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)2018-05-01 - 2023-04-30 - 759341 - VALID
Subjects: Adult, Male, Time Factors, Psychometrics, Science, Decision Making, Decision, General Physics and Astronomy, Receptors, N-Methyl-D-Aspartate, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Task Performance and Analysis, Human behaviour, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, 0303 health sciences, Multidisciplinary, Uncertainty, Brain, Bayes Theorem, Electroencephalography, General Chemistry, Female, Ketamine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cues, 030217 neurology & neurosurgery
Abstract: Making accurate decisions based on unreliable sensory evidence requires cognitive inference. Dysfunction of n-methyl-d-aspartate (NMDA) receptors impairs the integration of noisy input in theoretical models of neural circuits, but whether and how this synaptic alteration impairs human inference and confidence during uncertain decisions remains unknown. Here we use placebo-controlled infusions of ketamine to characterize the causal effect of human NMDA receptor hypofunction on cognitive inference and its neural correlates. At the behavioral level, ketamine triggers inference errors and elevated decision uncertainty. At the neural level, ketamine is associated with imbalanced coding of evidence and premature response preparation in electroencephalographic (EEG) activity. Through computational modeling of inference and confidence, we propose that this specific pattern of behavioral and neural impairments reflects an early commitment to inaccurate decisions, which aims at resolving the abnormal uncertainty generated by NMDA receptor hypofunction., In uncertain conditions, people make accurate decisions by considering multiple pieces of information. Here, the authors show that pharmacological n-methyl-d-aspartate (NMDA) receptor hypofunction is associated with elevated uncertainty and premature decisions based on unreliable evidence.
Published: 2022

10. Dark microbiome and extremely low organics in Atacama fossil delta unveil Mars life detection limits

Author: Armando Azua-Bustos, Alberto G. Fairén, Carlos González-Silva, Olga Prieto-Ballesteros, Daniel Carrizo, Laura Sánchez-García, Victor Parro, Miguel Ángel Fernández-Martínez, Cristina Escudero, Victoria Muñoz-Iglesias, Maite Fernández-Sampedro, Antonio Molina, Miriam García Villadangos, Mercedes Moreno-Paz, Jacek Wierzchos, Carmen Ascaso, Teresa Fornaro, John Robert Brucato, Giovanni Poggiali, Jose Antonio Manrique, Marco Veneranda, Guillermo López-Reyes, Aurelio Sanz-Arranz, Fernando Rull, Ann M. Ollila, Roger C. Wiens, Adriana Reyes-Newell, Samuel M. Clegg, Maëva Millan, Sarah Stewart Johnson, Ophélie McIntosh, Cyril Szopa, Caroline Freissinet, Yasuhito Sekine, Keisuke Fukushi, Koki Morida, Kosuke Inoue, Hiroshi Sakuma, Elizabeth Rampe, Centro de Astrobiologia [Madrid] (CAB), Instituto Nacional de Técnica Aeroespacial (INTA)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Instituto de Ciencias Biomédicas [Santiago] (ICB), Universidad Autonoma de Chile, Department of Astronomy [Ithaca], Cornell University [New York], Universidad de Tarapaca, Departamento de Ecología [Madrid], Universidad Autónoma de Madrid (UAM), Museo Nacional de Ciencias Naturales [Madrid] (MNCN), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), INAF - Osservatorio Astrofisico di Arcetri (OAA), Istituto Nazionale di Astrofisica (INAF), Universidad de Valladolid [Valladolid] (UVa), Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Department of Earth, Atmospheric, and Planetary Sciences [West Lafayette] (EAPS), Purdue University [West Lafayette], Southwest Sciences, Inc., GSFC Solar System Exploration Division, NASA Goddard Space Flight Center (GSFC), Department of Biology [Washington], Georgetown University [Washington] (GU), PLANETO - LATMOS, Laboratoire Atmosphères, Milieux, Observations Spatiales (LATMOS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Earth-Life Science Institute [Tokyo] (ELSI), Tokyo Institute of Technology [Tokyo] (TITECH), Institute of Nature and Environmental [Kanazawa], Kanazawa University (KU), National Institute for Materials Science (NIMS), NASA Johnson Space Center (JSC), NASA, European Commission, Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), and Agencia Estatal de Investigación (España)
Subjects: Multidisciplinary, [SDU]Sciences of the Universe [physics], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Identifying unequivocal signs of life on Mars is one of the most important objectives for sending missions to the red planet. Here we report Red Stone, a 163-100 My alluvial fan–fan delta that formed under arid conditions in the Atacama Desert, rich in hematite and mudstones containing clays such as vermiculite and smectites, and therefore geologically analogous to Mars. We show that Red Stone samples display an important number of microorganisms with an unusual high rate of phylogenetic indeterminacy, what we refer to as “dark microbiome”, and a mix of biosignatures from extant and ancient microorganisms that can be barely detected with state-of-the-art laboratory equipment. Our analyses by testbed instruments that are on or will be sent to Mars unveil that although the mineralogy of Red Stone matches that detected by ground-based instruments on the red planet, similarly low levels of organics will be hard, if not impossible to detect in Martian rocks depending on the instrument and technique used. Our results stress the importance in returning samples to Earth for conclusively addressing whether life ever existed on Mars., The research leading to these results is a contribution from the Project “MarsFirstWater”, funded by the European Research Council, Consolidator Grant no 818602 to AGF, and by the Human Frontiers Science Program grant n° RGY0066/2018 to A.A.-B. Additional funding provided was provided by MINECO grant PID2019-107442RB-C32 (O.P.-B. and A.M.), Grants-in-Aid for Scientific Research from the Japan Society for Promotion of Science grant numbers 17H06458 and 21H04515 (K.F.), grant numbers 17H06456, 17H06458, 20H00195, and 21H04515 (K.F. and Y.S.), Consejería de Educación e Investigación, Comunidad Autónoma de Madrid/European Social Fund program (MAFM), grant n° ESP2017-87690-C3-3-R (DC), Ramón y Cajal grant n° RYC2018-023943-I (L.S.-G.), AEI grant MDM-2017-0737 and MCIN/AEI grant PID2019-107442RB-C32 (V.M.-I.), MCIU/AEI (Spain) and FEDER (UE) grant n° PGC2018-094076-B-I00 (J.W. and C.A.), Italian Space Agency agreement 2017-48-H.0 (T.F., J.R.B. and G.P.), the Ministry of Science of Spain grant PID2019-107442RB-C31 (J.A.M., M.V., G.L.R., A.A. and F.R.), María Zambrano’ excellence grant program (CA3/RSUE/2021-00405), funded by the Spanish Ministry of Universities (MFM), NASA Mars Exploration Program contracts NNH13ZDA018O, NNH15AZ24I, NNH13ZDA018O and LANL Laboratory Directed Research and Development (LDRD) funding XX5V (A.M.O, R.C.W., A.R. and S.M.C.), NASA-GSFC grant NNX17AJ68G (M.M. and S.S.J.), NES focused on Sample Analysis at Mars of the Mars Science Laboratory mission, and Mars Organic Molecules Analyzer of the Exomars 2022 mission (O.M., C.S., and C.F.), and grants RTI2018-094368-B-I00 and MDM-2017-0737 Unidad de Excelencia “Maria de Maeztu”- Centro de Astrobiología (INTA-CSIC) by the Spanish Ministry of Science and Innovation/State Agency of Research MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe” (C.E., M.G.V., M.M.-P., and V.P.). R.C.W. thanks Dot Delapp for performing pre-processing of the LIBS data., With funding from the Spanish government through the "Severo Ochoa Center of Excellence" accreditation MDM-2017-0737.
Published: 2023

11. Globally invariant metabolism but density-diversity mismatch in springtails

Author: Anton M. Potapov, Carlos A. Guerra, Johan van den Hoogen, Anatoly Babenko, Bruno C. Bellini, Matty P. Berg, Steven L. Chown, Louis Deharveng, Ľubomír Kováč, Natalia A. Kuznetsova, Jean-François Ponge, Mikhail B. Potapov, David J. Russell, Douglas Alexandre, Juha M. Alatalo, Javier I. Arbea, Ipsa Bandyopadhyaya, Verónica Bernava, Stef Bokhorst, Thomas Bolger, Gabriela Castaño-Meneses, Matthieu Chauvat, Ting-Wen Chen, Mathilde Chomel, Aimee T. Classen, Jerome Cortet, Peter Čuchta, Ana Manuela de la Pedrosa, Susana S. D. Ferreira, Cristina Fiera, Juliane Filser, Oscar Franken, Saori Fujii, Essivi Gagnon Koudji, Meixiang Gao, Benoit Gendreau-Berthiaume, Diego F. Gomez-Pamies, Michelle Greve, I. Tanya Handa, Charlène Heiniger, Martin Holmstrup, Pablo Homet, Mari Ivask, Charlene Janion-Scheepers, Malte Jochum, Sophie Joimel, Bruna Claudia S. Jorge, Edite Jucevica, Olga Ferlian, Luís Carlos Iuñes de Oliveira Filho, Osmar Klauberg-Filho, Dilmar Baretta, Eveline J. Krab, Annely Kuu, Estevam C. A. de Lima, Dunmei Lin, Zoe Lindo, Amy Liu, Jing-Zhong Lu, María José Luciañez, Michael T. Marx, Matthew A. McCary, Maria A. Minor, Taizo Nakamori, Ilaria Negri, Raúl Ochoa-Hueso, José G. Palacios-Vargas, Melanie M. Pollierer, Pascal Querner, Natália Raschmanová, Muhammad Imtiaz Rashid, Laura J. Raymond-Léonard, Laurent Rousseau, Ruslan A. Saifutdinov, Sandrine Salmon, Emma J. Sayer, Nicole Scheunemann, Cornelia Scholz, Julia Seeber, Yulia B. Shveenkova, Sophya K. Stebaeva, Maria Sterzynska, Xin Sun, Winda I. Susanti, Anastasia A. Taskaeva, Madhav P. Thakur, Maria A. Tsiafouli, Matthew S. Turnbull, Mthokozisi N. Twala, Alexei V. Uvarov, Lisa A. Venier, Lina A. Widenfalk, Bruna R. Winck, Daniel Winkler, Donghui Wu, Zhijing Xie, Rui Yin, Douglas Zeppelini, Thomas W. Crowther, Nico Eisenhauer, Stefan Scheu, Johann-Friedrich Blumenbach Institut für Zoologie und Anthropologie, Georg-August-University = Georg-August-Universität Göttingen, A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences [Moscow] (RAS), German Centre for Integrative Biodiversity Research (iDiv), Institute of Biology, Leipzig University, Leipzig, Germany, Department of Environmental Systems Science [ETH Zürich] (D-USYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Botany and Zoology, Biosciences Center, Federal University of Rio Grande do Norte (UFRGS), Systems Ecology, Department of Ecological Science, Vrije Universiteit, Amsterdam, The Netherlands, Community and Conservation Ecology Group [Groningen], Université de Groningen, Securing Antarctica’s Environmental Future, School of Biological Sciences, Monash University, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Department of Zoology, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, Košice, Slovakia, Institute of Biology and Chemistry, Moscow Pedagogical State University, Moscow, Russia, Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Department of Soil Zoology, Senckenberg Society for Nature Research, Görlitz, Germany, Department of Soil Science, Centre for Agriculture and Veterinary Science, Santa Catarina State University (UDUESC Lages), Lages, SC, Brazil (UDUESC), Environmental Science Center, Qatar University, Doha, Qatar, Department of Sciences, CEPA Camargo, Astillero, Spain, Visva Bharati University, Bengal, India, Administración de Parques Nacionales, San Antonio, Argentina, School of Biology and Environmental Science - University College of Dublin, University College Dublin [Dublin] (UCD), UCD Earth Institute, University College Dublin, Unidad Multidisciplinaria de Docencia e Investigación, Facultad de Ciencias, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México, Etude et Compréhension de la biodiversité (ECODIV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institute of Entomology [České Budějovice] (BIOLOGY CENTRE CAS), Biology Centre of the Czech Academy of Sciences (BIOLOGY CENTRE CAS), Czech Academy of Sciences [Prague] (CAS)-Czech Academy of Sciences [Prague] (CAS), FiBL France, Department of Ecology and Evolutionary Biology, Museum of Zoology, The University of Michigan Research Museums Center, Ann Arbor, Michigan 48108-2228, USA, Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Departmento de Biología Zoología, Universidad Autónoma de Madrid, Madrid, Spain, Institute of Biology Bucharest, Romanian Academy, Department of General and Theoretical Ecology, University of Bremen, University of Bremen, Conservation Ecology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands, Department of Coastal Systems, Royal Netherlands Institute for Sea Research, ‘t Horntje, the Netherlands, Forestry and Forest Products Research Institute (FFPRI), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Ningbo University (NBU), Université du Québec en Outaouais (UQO), Universidad Nacional de Misiones, University of Pretoria [South Africa], Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland (HEdS-Ge / HES-SO), Section of Terrestrial Ecology, Department of Ecoscience, Aarhus University, Aarhus, Denmark, Instituto de Recursos Naturales y Agrobiología de Sevilla (IRNAS), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Tallinn University of Technology, Tartu College, Department of Biological Sciences, University of Cape Town, Cape Town, South Africa, Department of Entomology, Iziko Museums of South Africa, Cape Town, South Africa, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Institute of Biology, University of Latvia, Riga, Latvia, Department of Soil Science, Centre for Agriculture and Veterinary Science, Santa Catarina State University (UDESC-Lages), Lages, SC, Brazil, Department of Animal Science, Santa Catarina State University (UDESC Oeste), Chapecó, SC, Brazil, Department of Soil and Environment, Swedish University of Agricultural Sciences, Uppsala, Sweden, Climate Impacts Research Centre (CIRC), Umeå University, Estonian University of Life Sciences (EMU), Universidade Federal do Rio de Janeiro (UFRJ), Key Laboratory of the Three Gorges Reservoir Region’s Eco-Environment, Ministry of Education, Chongqing University, Chongqing, China, Department of Biology, University of Western Ontario, University of Western Ontario (UWO), Universidad Autónoma de Madrid (UAM), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Rice University [Houston], Wildlife and Ecology Group [New Zealand], Massey University, Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Japan, Department of Sustainable Crop Production (DI.PRO.VE.S.), Università Cattolica del Sacro Cuore, Piacenza, Italy, University of Cadiz, Netherlands Institute of Ecology - NIOO-KNAW (NETHERLANDS), Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria México, Natural History Museum [Vienna] (NHM), University of Natural Resources and Life Sciences, Department of Integrated Biology and Biodiversity Research, Institute of Zoology (BOKU), King Abdulaziz University, Department of Biological Sciences, Université du Québec à Montréal, Lancaster Environment Centre, Lancaster University, Smithsonian Tropical Research Institute, Senckenberg Museum of Natural History Görlitz, Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, Institute for Alpine Environment, Eurac Research, Ecology, University of Innsbruck, Leopold Franzens Universität Innsbruck - University of Innsbruck, State Nature Reserve 'Privolzhskaya Lesostep', Penza, Russia, Museum and Institute of Zoology, Polish Academy of Sciences, Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China, Institute of Biology Komi Science Centre UB RAS, University of Bern, Aristotle University of Thessaloniki, Great Lakes Forestry Centre, Canadian Forest Service, Natural Resources Canada, Sault Ste. Marie, ON, Canada, Department of Ecology, Swedish University of Agricultural Sciences, Uppsala, Sweden, Greensway AB, Uppsala, Sweden, Institute of Wildlife Biology and Game Management, University of Natural Resources and Life Sciences, Institute of Wildlife Management and Wildlife Biology, University of Sopron, Sopron, Hungary, Key laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China, Ministry of Education Key Laboratory of Vegetation Ecology, School of Life Sciences, Northeast Normal University, Changchun 130024, Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, School of Life Sciences, Northeast Normal University, Changchun 130024, Community Department, Helmholtz Center for Environmental Research, Halle, Germany, State University of Paraiba, Institute of Integrative Biology, Centre for Biodiversity and Sustainable Land-use [University of Göttingen] (CBL), Terrestrial Ecology (TE), Conservation Ecology Group, Govers group, Ecology & Evolution, Amsterdam Sustainability Institute, Systems Ecology, Animal Ecology, Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Unité Mixte de Recherche sur l'Ecosystème Prairial - UMR (UREP), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV]Life Sciences [q-bio], Soil Science, General Physics and Astronomy, 580 Plants (Botany), 000 Computer science, knowledge & systems, Markvetenskap, 590 Tiere (Zoologie), General Biochemistry, Genetics and Molecular Biology, Soil, terrestrial food web, SDG 13 - Climate Action, Humans, Animals, 000 Informatik, Wissen, Systeme, Macroecology, Arthropods, Tundra, Ecosystem, Ekologi, Multidisciplinary, Ecology, soil fertility, collembola, Biodiversity, General Chemistry, 580 Pflanzen (Botanik), Settore AGR/11 - ENTOMOLOGIA GENERALE E APPLICATA, [SDE]Environmental Sciences, 570 Life sciences, biology, 590 Animals (Zoology), 570 Biowissenschaften, Biologie
Abstract: Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning. The article is an outcome of the #GlobalCollembola community initiative that is voluntarily supported by researchers around the world. Data collection and analysis was supported by the Russian Science Foundation (19-74-00154 to A.P.) and by Deutsche Forschungsgemeinschaft (493345801 to A.P. and 192626868—SFB 990 to S.S.). We acknowledge support by the Open Access Publication Funds of the Göttingen University. The following funding bodies provided support for individual contributors: ARC SRIEAS Grant SR200100005 Securing Antarctica’s Environmental Future to S.L.C., Slovak Scientific Grant Agency VEGA 1/0438/22 to Ľ.K., RFBR 19-516-60002 to N.A.K., Carl Tryggers Stiftelse för Vetenskaplig Forskning and Qatar Petroleum to J.M.A., BIO 27 (2013-2014)-MAGyP and PICTO 2084 (2012)-ANPCyT to V.B., DAAD-19-10 and MSM200962001 to T.C., grant TE, PN-III-P1-1.1-TE-2019-0358 to C.F., NWO grant 821.01.015 to O.F., National Natural Sciences Foundation of China No 41471037 and 41871042 to M.G., BIO 27 (2013-2014), MAGyP; PICT 2084 (2012), FONCyT to D.F.G., NRF South African National Antarctic Programme grant 110734 to M.G., Natural Resources Canada (NRCan), EcoEnergy Innovation Initiative under the Office of Energy Research and Development, and the Natural Sciences and Engineering Research Council of Canada (NSERC) to I.T.H., L.A.V. and L.R., Independent Research Fund Denmark grant no. DFF-4002-00384 to M.H., Estonian Science Foundation G9145 to M.I., SA-France bilateral grant to C.J., SA (NRF)/Russia (RFBR) Joint Science and Technology Research Collaboration project no. 19-516-60002 (FRBR) and no. 118904 (NRF) to M.P. and C.J., European Research Council (ERC), European Union’s Horizon 2020 research and innovation programme (grant agreement no. 677232; to N.E.); iDiv, German Research Foundation (DFG–FZT 118, 202548816) to M.J. and N.E., French National Agency of Research (ANR) (JASSUR research project; ANR-12-VBDU-0011), «Ministère de l’Agriculture et de la Pêche» and «Ministère de l’Education Nationale de la Recherche et de la Technologie» (ACTA programme), «Ministère de l’Aménagement du Territoire et de l’Environnement» (Pnetox programme), EU-funded project, ECOGEN QLK5-CT-2002-01666 (www.ecogen.dk), “Agence de l’Environnement et de la Maîtrise de l'Énergie” (BIOINDICATEUR 2, BIOTECHNOSOL), ANDRA and GISFI (www.gisfi.fr) to S.J., GRR SER-BIODIV (Région Normandie, France) to MCha, ESF9258, B02 to A.K., Fundamental Research Funds for the Central Universities (grant no. 2018CDXYCH0014) to D.L., DFG 316045089 to J.L., Massey University Research Fund grant to M.A.M., DFG SCHE 376/38-2 to M.M.P., grant from the Austria Academy of Science: Heritage_2020-043_Modeling-Museum to P.Q., Slovak Scientific Grant Agency: VEGA Nos. 1/0441/03 and 1/3267/06 to N.R., Higher Education Commission of Pakistan to M.I.R., RSF 21-74-00126 to R.A.S., Austrian Federal Government and European Union (Rural Development 2014-2020) to J.S., АААА-А17-122040600025-2 to A.A.T., Brazilian Council for Scientific and Technological Development—CNPq (grant no. 152717/2016-1) to B.R.W., 309030/2018-8 to D.Z. and 305426/2018-4 to B.C.B., National Natural Science Foundation of China (31970434, 31772491) to N.N.G., Research and Innovation Support Foundation of Santa Catarina (FAPESC) (6.309/2011-6/FAPESC) and the CNPq (563251/2010-7/CNPq) to L.C.I.O.F., O.K.-F., the Latvian Council of Science Grants no. 90.108, 93.140, 96.0110, 01.0344 to E.J., CNPq for the Research Productivity Grant (305939/2018-1) to D.B., FPI-MICINN grant in the project INTERCAPA (CGL2014-56739-R) to P.H, the Natural Sciences and Engineering Research Council of Canada (NSERC) to Z.L., Ministry of Innovation and Technology of Hungary TKP2021-NKTA-43 to D.W. Authors are grateful to Penelope Greenslade for providing the literature on Australian Collembola communities. Authors are grateful to Frans Janssens for providing the global checklist of Collembola.
Published: 2023

12. Convergent morphology and divergent phenology promote the coexistence of Morpho butterfly species

Author: Camille Le Roy, Camille Roux, Elisabeth Authier, Hugues Parrinello, Héloïse Bastide, Vincent Debat, Violaine Llaurens, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Wageningen University and Research [Wageningen] (WUR), Évolution, Écologie et Paléontologie (Evo-Eco-Paleo) - UMR 8198 (Evo-Eco-Paléo (EEP)), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Evolution, génomes, comportement et écologie (EGCE), and Institut de Recherche pour le Développement (IRD)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Reproductive Isolation, Genetic Speciation, Behavioural ecology, Speciation, Science, General Physics and Astronomy, Evolutionary ecology, Article, General Biochemistry, Genetics and Molecular Biology, Spatio-Temporal Analysis, Animals, Wings, Animal, Life Science, Experimental Zoology, Ecosystem, Multidisciplinary, Biological Mimicry, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Courtship, General Chemistry, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Sympatry, Experimentele Zoologie, WIAS, Territoriality, Butterflies
Abstract: The coexistence of closely-related species in sympatry is puzzling because ecological niche proximity imposes strong competition and reproductive interference. A striking example is the widespread wing pattern convergence of several blue-banded Morpho butterfly species with overlapping ranges of distribution. Here we perform a series of field experiments using flying Morpho dummies placed in a natural habitat. We show that similarity in wing colour pattern indeed leads to interspecific territoriality and courtship among sympatric species. In spite of such behavioural interference, demographic inference from genomic data shows that sympatric closely-related Morpho species are genetically isolated. Mark-recapture experiments in the two most closely-related species unravel a strong temporal segregation in patrolling activity of males. Such divergence in phenology reduces the costs of reproductive interference while simultaneously preserving the benefits of convergence in non-reproductive traits in response to common ecological pressures. Henceforth, the evolution of multiple traits may favour species diversification in sympatry by partitioning niche in different dimensions., ‘Here, the authors use dummies of different Morpho butterfly species and sexes to investigate behaviour in patrolling butterflies, finding strong reproductive interference between species despite limited gene flow. They finally show that interference is mitigated by temporal partitioning, hence promoting the coexistence of sympatric Morpho species.’
Published: 2021

13. Histone variant H2A.Z regulates zygotic genome activation

Author: Alejandro Gomez-Auli, Nicola Iovino, Michael Rauer, Dafne Ibarra-Morales, Mariana Schulte-Sasse, Francesco Cardamone, Leily Rabbani, Piergiuseppe Quarato, Fides Zenk, Germano Cecere, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Open Access funding enabled and organized by Projekt DEAL, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Epigenomics, Male, Zygote, MESH: Drosophila, [SDV]Life Sciences [q-bio], MESH: Epigenomics, General Physics and Astronomy, RNA polymerase II, Genome, MESH: Down-Regulation, Histones, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, MESH: Embryonic Development, MESH: Animals, Histone variants, Adenosine Triphosphatases, MESH: Histones, 0303 health sciences, Genes, Essential, Multidisciplinary, biology, MESH: Histone Chaperones, Gene Expression Regulation, Developmental, Chromatin, Cell biology, Housekeeping gene, Histone, Gene Knockdown Techniques, Chromatin Immunoprecipitation Sequencing, MESH: Cell Division, Drosophila, Female, RNA Polymerase II, MESH: Transcription Initiation Site, Transcription Initiation Site, MESH: Chromatin Immunoprecipitation Sequencing, Cell Division, Transcriptional Activation, Epigenetic memory, animal structures, Science, Down-Regulation, Embryonic Development, Article, General Biochemistry, Genetics and Molecular Biology, MESH: Chromatin, 03 medical and health sciences, MESH: Adenosine Triphosphatases, Animals, Histone Chaperones, MESH: Genome, Gene, MESH: Genes, Essential, 030304 developmental biology, Pioneer factor, General Chemistry, MESH: Gene Knockdown Techniques, MESH: Male, MESH: RNA Polymerase II, biology.protein, MESH: Transcriptional Activation, Maternal to zygotic transition, MESH: Zygote, MESH: Female, 030217 neurology & neurosurgery
Abstract: During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development; still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z. H2A.Z enrichment precedes ZGA and RNA Polymerase II loading onto chromatin. In vivo knockdown of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that H2A.Z is essential for the de novo establishment of transcriptional programs during ZGA via chromatin reorganization., Nature Communications, 12 (1), ISSN:2041-1723
Published: 2021

14. Morphological control enables nanometer-scale dissection of cell-cell signaling complexes

Author: Liam P. Dow, Guido Gaietta, Yair Kaufman, Mark F. Swift, Moara Lemos, Kerry Lane, Matthew Hopcroft, Armel Bezault, Cécile Sauvanet, Niels Volkmann, Beth L. Pruitt, Dorit Hanein, University of California [Santa Barbara] (UC Santa Barbara), University of California (UC), The Scintillon Institute, Études structurales de machines moléculaires in cellulo - Structural studies of macromolecular machines in cellula, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagerie structurale - Structural Image Analysis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was supported National Institutes of Health grants R01 GM119948 (N.V., D.H., and B.L.P.), NSF CMMI-183476 (B.L.P.) and seeding funding from UCSB CNSI. KL was supported by NSF GRFP and UCSB fellowship funding., LPD acknowledges useful conversations with Dr. Leeya Engel (Stanford University). G.G. and D.H. thank the Nelson lab for their generous gift of the pEGFP-C1-ACAT plasmid and Dr. Kathleen A Siemers for helping with the plasmid, characterization work, and for providing the anti-alpha catenin antibody used in the immunofluorescence experiments. The authors acknowledge the use of the Nanostructures Cleanroom Facility and Microfluidics Lab within the California NanoSystems Institute, supported by the University of California, Santa Barbara and the University of California, Office of the President. The authors acknowledge the use of the Titan Krios, Tecnai Spirit T12 and auxiliary equipment at the cryo-EM unit of the Sanford Burnham Prebys Medical Discovery Institute, which was created in part with the support of US National Institutes of Health Grant S10-OD012372 (D.H.) and Pew Charitable Trust 864K625 innovation award funds (D.H.). The authors acknowledge access to the Titan Krios, Glacios, and Aquilos-2 instruments at the NanoImaging Core of the Institut Pasteur. The NanoImaging Core at Institut Pasteur was created with the help of a grant from the French Government’s Investissements d’Avenir program (EQUIPEX CACSICE - Centre d’analyse de systèmes complexes dans les environnements complexes, ANR-11-EQPX-0008)., and ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011)
Subjects: Multidisciplinary, Image Processing, 1.1 Normal biological development and functioning, [SDV]Life Sciences [q-bio], Cryoelectron Microscopy, Proteins, General Physics and Astronomy, Bioengineering, General Chemistry, Carbon, General Biochemistry, Genetics and Molecular Biology, Computer-Assisted, Underpinning research, Nanotechnology, Generic health relevance, Signal Transduction
Abstract: Protein micropatterning enables robust control of cell positioning on electron-microscopy substrates for cryogenic electron tomography (cryo-ET). However, the combination of regulated cell boundaries and the underlying electron-microscopy substrate (EM-grids) provides a poorly understood microenvironment for cell biology. Because substrate stiffness and morphology affect cellular behavior, we devised protocols to characterize the nanometer-scale details of the protein micropatterns on EM-grids by combining cryo-ET, atomic force microscopy, and scanning electron microscopy. Measuring force displacement characteristics of holey carbon EM-grids, we found that their effective spring constant is similar to physiological values expected from skin tissues. Despite their apparent smoothness at light-microscopy resolution, spatial boundaries of the protein micropatterns are irregular at nanometer scale. Our protein micropatterning workflow provides the means to steer both positioning and morphology of cell doublets to determine nanometer details of punctate adherens junctions. Our workflow serves as the foundation for studying the fundamental structural changes governing cell-cell signaling.
Published: 2022

15. Multiple drivers and lineage-specific insect extinctions during the Permo–Triassic

Author: Corentin Jouault, André Nel, Vincent Perrichot, Frédéric Legendre, Fabien L. Condamine, Géosciences Rennes (GR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Multidisciplinary, General Physics and Astronomy, General Chemistry, [SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology, General Biochemistry, Genetics and Molecular Biology
Abstract: The Permo–Triassic interval encompasses three extinction events including the most dramatic biological crisis of the Phanerozoic, the latest Permian mass extinction. However, their drivers and outcomes are poorly quantified and understood for terrestrial invertebrates, which we assess here for insects. We find a pattern with three extinctions: the Roadian/Wordian (≈266.9 Ma; extinction of 64.5% insect genera), the Permian/Triassic (≈252 Ma; extinction of 82.6% insect genera), and the Ladinian/Carnian boundaries (≈237 Ma; extinction of 74.8% insect genera). We also unveil a heterogeneous effect of these extinction events across the major insect clades. Because extinction events have impacted Permo–Triassic ecosystems, we investigate the influence of abiotic and biotic factors on insect diversification dynamics and find that changes in floral assemblages are likely the strongest drivers of insects’ responses throughout the Permo–Triassic. We also assess the effect of diversity dependence between three insect guilds; an effect ubiquitously found in current ecosystems. We find that herbivores held a central position in the Permo–Triassic interaction network. Our study reveals high levels of insect extinction that profoundly shaped the evolutionary history of the most diverse non-microbial lineage.
Published: 2022

16. CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells

Author: Charlotte A. James, Yuexin Xu, Melissa S. Aguilar, Lichen Jing, Erik D. Layton, Martine Gilleron, Adriaan J. Minnaard, Thomas J. Scriba, Cheryl L. Day, Edus H. Warren, David M. Koelle, Chetan Seshadri, Chemical Biology 2, Department of Engineering Mathematics, University of Bristol, University of Bristol [Bristol], Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Cape Town, University of Washington [Seattle], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Groningen [Groningen], Emory University [Atlanta, GA], Benaroya Research Institute [Seattle] (BRI), and Tuberculosis Research and Training Center
Subjects: CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, CD3 Complex, Science, Primary Cell Culture, CD1, T cells, General Physics and Astronomy, Gene Expression, CD8-Positive T-Lymphocytes, Major histocompatibility complex, Lymphocyte Activation, Jurkat cells, General Biochemistry, Genetics and Molecular Biology, Article, Antigens, CD1, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Transduction, Genetic, Cytotoxic T cell, Humans, Tuberculosis, Avidity, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Chemistry, T-cell receptor, General Chemistry, Mycobacterium tuberculosis, Molecular biology, Cellular immunity, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, biology.protein, Sample collection, Glycolipids, Protein Multimerization, MHC, CD8, 030215 immunology, Protein Binding
Abstract: T cells recognize mycobacterial glycolipid (mycolipid) antigens presented by CD1b molecules, but the role of CD4 and CD8 co-receptors in mycolipid recognition is unknown. Here we show CD1b-mycolipid tetramers reveal a hierarchy in which circulating T cells expressing CD4 or CD8 co-receptor stain with a higher tetramer mean fluorescence intensity than CD4-CD8- T cells. CD4+ primary T cells transduced with mycolipid-specific T cell receptors bind CD1b-mycolipid tetramer with a higher fluorescence intensity than CD8+ primary T cells. The presence of either CD4 or CD8 also decreases the threshold for interferon-γ secretion. Co-receptor expression increases surface expression of CD3ε, suggesting a mechanism for increased tetramer binding and activation. Targeted transcriptional profiling of mycolipid-specific T cells from individuals with active tuberculosis reveals canonical markers associated with cytotoxicity among CD8+ compared to CD4+ T cells. Thus, expression of co-receptors modulates T cell receptor avidity for mycobacterial lipids, leading to in vivo functional diversity during tuberculosis disease., CD4 and CD8 co-receptors are routinely used to define distinct functional and phenotypic lineages of T cells. Here the authors show CD4 and CD8 also modulate the functional avidity of the CD1b-restricted response to mycobacterial lipid antigens
Published: 2022

17. Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction

Author: Matthias Titeux, David Michonneau, Nicolas Pallet, Armance Marchal, Soëli Charbonnier, Juliette Leon, Julien Zuber, Katrin Vogt, Marianne Delville, Hélène Vinçon, Ivan Nemazanyy, Isabelle André, Jean-Luc Taupin, Christophe Legendre, Birgit Sawitzki, Tifanie Blein, Marina Cavazzana, Dany Anglicheau, Sylvain Latour, Baptiste Lamarthée, Lucas Rabaux, Emmanuelle Six, Emmanuel Martin, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Harvard Medical School [Boston] (HMS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and LATOUR, Sylvain
Subjects: Male, Adoptive cell transfer, [SDV]Life Sciences [q-bio], Cell, Graft vs Host Disease, Translational immunology, General Physics and Astronomy, Mice, SCID, Signal transduction, Immunotherapy, Adoptive, T-Lymphocytes, Regulatory, Immune tolerance, Jurkat Cells, 0302 clinical medicine, Mice, Inbred NOD, Mice, Knockout, 0303 health sciences, Receptors, Chimeric Antigen, Multidisciplinary, Chemistry, TOR Serine-Threonine Kinases, CD28, food and beverages, hemic and immune systems, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Immunosuppressive Agents, Science, Transplantation, Heterologous, chemical and pharmacologic phenomena, Article, General Biochemistry, Genetics and Molecular Biology, Tumor Necrosis Factor Receptor Superfamily, Member 9, 03 medical and health sciences, CD28 Antigens, In vivo, HLA-A2 Antigen, medicine, Animals, Humans, Tonic (music), PI3K/AKT/mTOR pathway, 030304 developmental biology, Sirolimus, Allotransplantation, General Chemistry, Chimeric antigen receptor, human activities, 030215 immunology
Abstract: The use of chimeric antigen receptor (CAR)-engineered regulatory T cells (Tregs) has emerged as a promising strategy to promote immune tolerance. However, in conventional T cells (Tconvs), CAR expression is often associated with tonic signaling, which can induce CAR-T cell dysfunction. The extent and effects of CAR tonic signaling vary greatly according to the expression intensity and intrinsic properties of the CAR. Here, we show that the 4-1BB CSD-associated tonic signal yields a more dramatic effect in CAR-Tregs than in CAR-Tconvs with respect to activation and proliferation. Compared to CD28 CAR-Tregs, 4-1BB CAR-Tregs exhibit decreased lineage stability and reduced in vivo suppressive capacities. Transient exposure of 4-1BB CAR-Tregs to a Treg stabilizing cocktail, including an mTOR inhibitor and vitamin C, during ex vivo expansion sharply improves their in vivo function and expansion after adoptive transfer. This study demonstrates that the negative effects of 4-1BB tonic signaling in Tregs can be mitigated by transient mTOR inhibition., Chimeric antigen receptor engineering in T cells has been shown to be of great potential therapeutic benefit in a range of immune pathologies, although the functionality of such cell therapies can be limited due to tonic signalling and the induction of dysfunction. Here the authors show transient inhibition of mTOR can rescue their 41-BB-CAR-Tregs from tonic signalling-induced dysfunction.
Published: 2021

18. The Tharsis mantle source of depleted shergottites revealed by 90 million impact craters

Author: Eleanor K. Sansom, Martin C. Towner, K. Servis, David Baratoux, Phil A. Bland, Anthony Lagain, Luc Serge Doucet, Gretchen Benedix, Hadrien A. R. Devillepoix, A. Rajsic, Katarina Miljković, Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)
Subjects: Martian, geography, Multidisciplinary, geography.geographical_feature_category, Science, Volcanology, General Physics and Astronomy, Scientific data, General Chemistry, Mars Exploration Program, Article, General Biochemistry, Genetics and Molecular Biology, Mantle (geology), Astrobiology, Impact crater, Volcano, Meteorite, [SDU]Sciences of the Universe [physics], Meteoritics, Inner planets, Geology, Tharsis
Abstract: The only martian rock samples on Earth are meteorites ejected from the surface of Mars by asteroid impacts. The locations and geological contexts of the launch sites are currently unknown. Determining the impact locations is essential to unravel the relations between the evolution of the martian interior and its surface. Here we adapt a Crater Detection Algorithm that compile a database of 90 million impact craters, allowing to determine the potential launch position of these meteorites through the observation of secondary crater fields. We show that Tooting and 09-000015 craters, both located in the Tharsis volcanic province, are the most likely source of the depleted shergottites ejected 1.1 million year ago. This implies that a major thermal anomaly deeply rooted in the mantle under Tharsis was active over most of the geological history of the planet, and has sampled a depleted mantle, that has retained until recently geochemical signatures of Mars’ early history., The ejection sites of the martian meteorites are still unknown. Here, the authors build a database of 90 million craters and show that Tharsis region is the most likely source of depleted shergottites ejected 1.1 Ma ago, thus confirming that some portions of the mantle were recently anomalously hot.
Published: 2021

19. A medullary centre for lapping in mice

Author: Dempsey, Bowen, Sungeelee, Selvee, Bokiniec, Phillip, Chettouh, Zoubida, Diem, Séverine, Autran, Sandra, Harrell, Evan R., Poulet, James F. A., Birchmeier, Carmen, Carey, Harry, Genovesio, Auguste, McMullan, Simon, Goridis, Christo, Fortin, Gilles, Brunet, Jean-François, Fortin, Gilles, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de l'Audition [Paris] (IDA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Macquarie University [Sydney], ANR-17-CE16-0006,HEARTBRAIN,Développement et Physiologie des Neurones Intrinsèques du Cœur(2017), ANR-19-CE16-0029,HOMORESP,Résaux neuronaux homotypiques du contrôle respiratoire(2019), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Macquarie University, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Male, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Science, Action Potentials, Neural circuits, behavioral disciplines and activities, Article, Mice, Tongue, Animals, Central pattern generators, Homeodomain Proteins, Mice, Knockout, Motor Neurons, Medulla Oblongata, Reticular Formation, digestive, oral, and skin physiology, fungi, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, food and beverages, Feeding Behavior, Jaw, Female, Function and Dysfunction of the Nervous System, Brain Stem, Transcription Factors
Abstract: It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRtPhox2b and Peri5Atoh1, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve. They are premotor to all jaw-opening and tongue muscles. Stimulation of either, in awake animals, opens the jaw, while IRtPhox2b alone also protracts the tongue. Moreover, stationary stimulation of IRtPhox2b entrains a rhythmic alternation of tongue protraction and retraction, synchronized with jaw opening and closing, that mimics lapping. Finally, fiber photometric recordings show that IRtPhox2b is active during volitional lapping. Our study identifies one of the subcortical nuclei underpinning a stereotyped feeding behavior., Orofacial movements for feeding can be triggered, coordinated and rhythmically organised at the level of the brainstem. Here, the authors show two nuclei can organise the stereotyped movements for ingesting fluids in mammals, these neuronal groups are marked by expression of Phox2b and are located in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve.
Published: 2021

20. Interaction of two MADS-box genes leads to growth phenotype divergence of all-flesh type of tomatoes

Author: Huang, Baowen, Hu, Guojian, Wang, Keke, Frasse, Pierre, Maza, Elie, Djari, Anis, Deng, Wei, Pirrello, Julien, Burlat, Vincent, Pons, Clara, Granell, Antonio, Li, Zhengguo, van der Rest, Benoît, Bouzayen, Mondher, Génomique et Biotechnologie des Fruits (GBF), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Recherche en Sciences Végétales (LRSV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Génomique et Biotechnologie des Fruits, Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Chongqing University [Chongqing], Dynamique et Evolution des Parois cellulaires végétales, Universitat Politècnica de València (UPV), European Project: 679796,H2020,H2020-SFS-2015-2,TomGEM(2016), European Project: 101000716,HARNESSTOM, École nationale supérieure agronomique de Toulouse (ENSAT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), and Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Agricultural genetics, Gene Expression Profiling, Science, fungi, Genetic Variation, food and beverages, MADS Domain Proteins, Molecular engineering in plants, Article, Plant breeding, Phenotype, Solanum lycopersicum, Cell Wall, Gene Expression Regulation, Plant, Fruit, Mutation, Plant development, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Cell Proliferation, Plant Proteins
Abstract: [EN] All-flesh tomato cultivars are devoid of locular gel and exhibit enhanced firmness and improved postharvest storage. Here, we show that SlMBP3 is a master regulator of locular tissue in tomato fruit and that a deletion at the gene locus underpins the All-flesh trait. Intriguingly, All-flesh varieties lack the deleterious phenotypes reported previously for SlMBP3 under-expressing lines and which preclude any potential commercial use. We resolve the causal factor for this phenotypic divergence through the discovery of a natural mutation at the SlAGL11 locus, a close homolog of SlMBP3. Misexpressing SlMBP3 impairs locular gel formation through massive transcriptomic reprogramming at initial phases of fruit development. SlMBP3 influences locule gel formation by controlling cell cycle and cell expansion genes, indicating that important components of fruit softening are determined at early pre-ripening stages. Our findings define potential breeding targets for improved texture in tomato and possibly other fleshy fruits. The all-flesh type of tomato fruits is caused by mutation of the MBP3 gene, however, knocking down MBP3 in certain genotypes also affect plant and fruit development. Here, the authors show that a natural mutation of AGL11, a close homolog of MBP3, is responsible for the phenotypic divergence., The authors are grateful to L. Lemonnier and D. Saint-Martin for transformation and cultivation of tomato plants and GeT-PlaGe core facility (INRAe Toulouse) for ChIP deep sequencing. The authors also want to thank Dr. Christian Chevalier (INRAE et Univsersite de Bordeaux) for helping in analyzing genes related to cell cycle, cell division, and endoreduplication in tomato. This research was supported by the EU H2020 TomGEM 679796 and HARNESSTOM 101000716 projects.
Published: 2021

21. Analog programing of conducting-polymer dendritic interconnections and control of their morphology

Author: Fabien Alibart, Anna Susloparova, Sébastien Pecqueur, Kamila Janzakova, Mahdi Ghazal, Yannick Coffinier, Ankush Kumar, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Nanostructures, nanoComponents & Molecules - IEMN (NCM - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), NanoBioInterfaces - IEMN (NBI - IEMN), Laboratoire Nanotechnologies et Nanosystèmes [Sherbrooke] (LN2), Université de Sherbrooke (UdeS)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), European Commission: H2020-EU.1.1.ERC project IONOS (# GA 773228-recipient: F.A.)., Renatech Network, European Project: 773228,H2020,ERC-2017-COG,IONOS(2018), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), and Université de Lyon-Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon)
Subjects: Bridging (networking), Computer science, Science, General Physics and Astronomy, FOS: Physical sciences, Image processing, 02 engineering and technology, Applied Physics (physics.app-ph), 010402 general chemistry, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Article, Electrochemistry, Electronic devices, Electronics, [PHYS.COND.CM-DS-NN]Physics [physics]/Condensed Matter [cond-mat]/Disordered Systems and Neural Networks [cond-mat.dis-nn], Biochip, Emulation, Multidisciplinary, Process (computing), General Chemistry, Physics - Applied Physics, Disordered Systems and Neural Networks (cond-mat.dis-nn), [CHIM.MATE]Chemical Sciences/Material chemistry, Condensed Matter - Disordered Systems and Neural Networks, 021001 nanoscience & nanotechnology, Electrical and electronic engineering, 0104 chemical sciences, [SPI.TRON]Engineering Sciences [physics]/Electronics, Neuromorphic engineering, Duty cycle, 0210 nano-technology, Biological system
Abstract: Although materials and processes are different from biological cells’, brain mimicries led to tremendous achievements in parallel information processing via neuromorphic engineering. Inexistent in electronics, we emulate dendritic morphogenesis by electropolymerization in water, aiming in operando material modification for hardware learning. Systematic study of applied voltage-pulse parameters details on tuning independently morphological aspects of micrometric dendrites’: fractal number, branching degree, asymmetry, density or length. Growths time-lapse image processing shows spatial features to be dynamically dependent, and expand distinctively before and after conductive bridging with two electro-generated dendrites. Circuit-element analysis and impedance spectroscopy confirms their morphological control in temporal windows where growth kinetics is finely perturbed by the input frequency and duty cycle. By the emulation of one’s most preponderant mechanisms for brain’s long-term memory, its implementation in vicinity of sensing arrays, neural probes or biochips shall greatly optimize computational costs and recognition required to classify high-dimensional patterns from complex environments., Despite advances in brain-inspired computing, existing electronics use top-down processes that do not compare with neural connections in the brain. Here, the authors report an electrically-tunable electropolymerization process that emulates and controls neural dendritic morphogenesis.
Published: 2021

22. Multiple evolutionary origins and losses of tooth complexity in squamates

Author: Julien Clavel, Nicolas Di-Poï, Fabien Lafuma, Ian J. Corfe, HiLIFE - Institute of Biotechnology [Helsinki] (BI), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Geological Survey of Finland, Équipe 6 - Paléontologie, Paléoécologie, Paléobiogéographie, Évolution (P3E), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Department of Life Sciences, The Natural History Museum [London] (NHM), Vertebrate Evolution, Development and Regeneration Group, Institute of Biotechnology, and Helsinki Institute of Life Science HiLIFE
Subjects: 0106 biological sciences, REPTILES LIZARDS, Evolution, Speciation, Science, Biology, 010603 evolutionary biology, 01 natural sciences, Article, 03 medical and health sciences, TEETH, Extant taxon, stomatognathic system, biology.animal, Genetic algorithm, Animals, R PACKAGE, Dietary change, PHYLOGENIES, Phylogeny, 030304 developmental biology, Mammals, 0303 health sciences, Fossils, Palaeontology, Vertebrate, Phylogenetic comparative methods, FOSSIL RECORD, Biological Evolution, ADAPTIVE RADIATION, Diet, Phylogenetics, stomatognathic diseases, EXTINCTION, Phenotype, Evolutionary biology, 1181 Ecology, evolutionary biology, Vertebrates, Cusp (anatomy), Identification (biology), Mammal, DIVERSIFICATION, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, HERBIVORY, Tooth
Abstract: Teeth act as tools for acquiring and processing food, thus holding a prominent role in vertebrate evolution. In mammals, dental-dietary adaptations rely on tooth complexity variations controlled by cusp number and pattern. Complexity increase through cusp addition has dominated the diversification of mammals. However, studies of Mammalia alone cannot reveal patterns of tooth complexity conserved throughout vertebrate evolution. Here, we use morphometric and phylogenetic comparative methods across fossil and extant squamates to show they also repeatedly evolved increasingly complex teeth, but with more flexibility than mammals. Since the Late Jurassic, multiple-cusped teeth evolved over 20 times independently from a single-cusped common ancestor. Squamates frequently lost cusps and evolved varied multiple-cusped morphologies at heterogeneous rates. Tooth complexity evolved in correlation with changes in plant consumption, resulting in several major increases in speciation. Complex teeth played a critical role in vertebrate evolution outside Mammalia, with squamates exemplifying a more labile system of dental-dietary evolution., Tooth morphology has provided many insights into the tempo and mode of dietary evolution in mammals. A study of fossil and extant squamates shows that this group also repeatedly evolved increasingly complex teeth with more flexibility than mammals, and that higher tooth complexity and herbivory likely led to higher speciation rates.
Published: 2021

23. Regulatory T cells promote cancer immune-escape through integrin αvβ8-mediated TGF-β activation

Author: Lainé, Alexandra, Labiad, Ossama, Hernandez-Vargas, Hector, This, Sébastien, Sanlaville, Amélien, Léon, Sophie, Dalle, Stéphane, Sheppard, Dean, Travis, Mark A., Paidassi, Helena, Marie, Julien C., Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Manchester [Manchester], Paidassi, Helena, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer microenvironment, Male, Mice, Knockout, Integrins, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, T-Lymphocytes, Regulatory, Article, Mice, Inbred C57BL, Mice, Lymphocyte differentiation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Transforming Growth Factor beta, Neoplasms, Tumor Microenvironment, Tumour immunology, Animals, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Immunosuppression
Abstract: Presence of TGFβ in the tumor microenvironment is one of the most relevant cancer immune-escape mechanisms. TGFβ is secreted in an inactive form, and its activation within the tumor may depend on different cell types and mechanisms than its production. Here we show in mouse melanoma and breast cancer models that regulatory T (Treg) cells expressing the β8 chain of αvβ8 integrin (Itgβ8) are the main cell type in the tumors that activates TGFβ, produced by the cancer cells and stored in the tumor micro-environment. Itgβ8 ablation in Treg cells impairs TGFβ signalling in intra-tumoral T lymphocytes but not in the tumor draining lymph nodes. Successively, the effector function of tumor infiltrating CD8+ T lymphocytes strengthens, leading to efficient control of tumor growth. In cancer patients, anti-Itgβ8 antibody treatment elicits similar improved cytotoxic T cell activation. Thus, this study reveals that Treg cells work in concert with cancer cells to produce bioactive-TGFβ and to create an immunosuppressive micro-environment., TGFβ is secreted in an inactive form in the tumor microenvironment. Authors here show that although TGFβ is produced mainly by cancer cells, regulatory T cells are necessary for its activation via expression of the b8 chain of avb8 integrin. Thus, both cell types contribute to TGFβ dependent tumor growth.
Published: 2021

24. Vacuum-field-induced THz transport gap in a carbon nanotube quantum dot

Author: Audrey Cottet, Matthieu C. Dartiailh, Jérôme Tignon, Takis Kontos, M. M. Desjardins, L. C. Contamin, Matthieu R. Delbecq, Kazushi Yoshida, S. Massabeau, Kazuhiko Hirakawa, Juliette Mangeney, Tino Cubaynes, Zaki Leghtas, Sébastien Balibar, Simon Messelot, Sukhdeep Dhillon, Federico Valmorra, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institute of Industrial Science (IIS), The University of Tokyo (UTokyo), Physique Mésoscopique, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Nano-THz, Centre Automatique et Systèmes (CAS), MINES ParisTech - École nationale supérieure des mines de Paris, Théorie de la Matière Condensée, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris)
Subjects: Photon, Electronic properties and materials, Band gap, Science, General Physics and Astronomy, Physics::Optics, 02 engineering and technology, Carbon nanotube, 7. Clean energy, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Article, law.invention, law, 0103 physical sciences, Spontaneous emission, 010306 general physics, Single photons and quantum effects, Quantum fluctuation, Physics, Quantum optics, [PHYS]Physics [physics], Multidisciplinary, business.industry, General Chemistry, 021001 nanoscience & nanotechnology, Carbon nanotube quantum dot, Quantum technology, Optoelectronics, 0210 nano-technology, business
Abstract: The control of light-matter interaction at the most elementary level has become an important resource for quantum technologies. Implementing such interfaces in the THz range remains an outstanding problem. Here, we couple a single electron trapped in a carbon nanotube quantum dot to a THz resonator. The resulting light-matter interaction reaches the deep strong coupling regime that induces a THz energy gap in the carbon nanotube solely by the vacuum fluctuations of the THz resonator. This is directly confirmed by transport measurements. Such a phenomenon which is the exact counterpart of inhibition of spontaneous emission in atomic physics opens the path to the readout of non-classical states of light using electrical current. This would be a particularly useful resource and perspective for THz quantum optics., Strong light-matter coupling has been realized at the level of single atoms and photons throughout most of the electromagnetic spectrum, except for the THz range. Here, the authors report a THz-scale transport gap, induced by vacuum fluctuations in carbon nanotube quantum dot through the deep strong coupling of a single electron to a THz resonator.
Published: 2021

25. Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state

Author: Emmanuel Margeat, Robert B. Quast, Anne-Marinette Cao, Philippe Rondard, Fataneh Fatemi, Jean-Philippe Pin, Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ecole Polytechnique Fédérale de Lausanne (EPFL), Shahid Beheshti University, Institut de Génomique Fonctionnelle (IGF), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Guerineau, Nathalie C., Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Margeat, Emmanuel
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Protein Conformation, cooperativity, [SDV]Life Sciences [q-bio], Gene Expression, General Physics and Astronomy, Molecular neuroscience, insights, Disaccharides, Receptors, Metabotropic Glutamate, taste, 0302 clinical medicine, G protein-coupled receptors, Glucosides, Catalytic Domain, Fluorescence Resonance Energy Transfer, Amino Acids, Receptor, Micelles, 0303 health sciences, Multidisciplinary, Chemistry, Glutamate receptor, Molecular conformation, Recombinant Proteins, Single Molecule Imaging, stabilization, 3. Good health, protein-coupled receptors, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV] Life Sciences [q-bio], Transmembrane domain, Indans, single-molecule fret, Cholesterol Esters, Allosteric Site, Protein Binding, Agonist, Allosteric modulator, Octoxynol, medicine.drug_class, Science, Gi alpha subunit, Allosteric regulation, mechanism, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Glutamic Acid, Diosgenin, Article, General Biochemistry, Genetics and Molecular Biology, Bridged Bicyclo Compounds, 03 medical and health sciences, Single-molecule biophysics, Allosteric Regulation, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, G protein-coupled receptor, Biphenyl Compounds, Cell Membrane, General Chemistry, Bridged Bicyclo Compounds, Heterocyclic, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, HEK293 Cells, Xanthenes, Metabotropic glutamate receptor, Biophysics, activation, Glycolipids, Protein Multimerization, 030217 neurology & neurosurgery
Abstract: Here, the authors use smFRET to assess the structural dynamics of metabotropic glutamate receptor mGlu2 and show that a positive allosteric modulator or the Gi protein stabilize mGlu2 in the glutamate-induced active state, leading to the full activation of the receptor., Much hope in drug development comes from the discovery of positive allosteric modulators (PAM) that display target subtype selectivity and act by increasing agonist potency and efficacy. How such compounds can allosterically influence agonist action remains unclear. Metabotropic glutamate receptors (mGlu) are G protein-coupled receptors that represent promising targets for brain diseases, and for which PAMs acting in the transmembrane domain have been developed. Here, we explore the effect of a PAM on the structural dynamics of mGlu2 in optimized detergent micelles using single molecule FRET at submillisecond timescales. We show that glutamate only partially stabilizes the extracellular domains in the active state. Full activation is only observed in the presence of a PAM or the G(i) protein. Our results provide important insights on the role of allosteric modulators in mGlu activation, by stabilizing the active state of a receptor that is otherwise rapidly oscillating between active and inactive states.
Published: 2021

26. CryoEM structure and assembly mechanism of a bacterial virus genome gatekeeper

Author: Igor Orlov, Stéphane Roche, Sandrine Brasilès, Natalya Lukoyanova, Marie-Christine Vaney, Paulo Tavares, Elena V. Orlova, Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Glasgow, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Birkbeck College [University of London], Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University College of London [London] (UCL), Part of this work was supported by institutional funding from CNRS., and We thank Dr. D. Houldershaw and Y. Goudetsidis for computer support at Birkbeck throughout the duration of the project. Cryo-EM samples were prepared and optimised at the ISMB EM facility at Birkbeck College, with financial support from Wellcome Trust (079605/2/06/2). We acknowledge Diamond Light Source for access and support of the cryo-EM facilities at the UK National electron Bio-Imaging Centre (eBIC, under proposal EM14704) funded by the Wellcome Trust, the Medical Research Council UK, and the Biotechnology and Biological Sciences Research Council. We are grateful to Dr. Y. Chaban for his assistance with the data collection at the eBIC. We thank Dr. A. Isidro (VMS, CNRS, Gif-sur-Yvette, France) for a sample of HSV-1 C-capsids and Dr. R. Lurz (MPIMG, Berlin, Germany) for kindly providing the micrographs shown in Fig. 6.
Subjects: Viral Proteins, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Virus Assembly, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cryoelectron Microscopy, Electron microscopy, Phage biology, General Physics and Astronomy, Bacteriophages, Genome, Viral, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Numerous viruses package their dsDNA genome into preformed capsids through a portal gatekeeper that is subsequently closed. We report the structure of the DNA gatekeeper complex of bacteriophage SPP1 (gp612gp1512gp166) in the post-DNA packaging state at 2.7 Å resolution obtained by single particle cryo-electron microscopy. Comparison of the native SPP1 complex with assembly-naïve structures of individual components uncovered the complex program of conformational changes leading to its assembly. After DNA packaging, gp15 binds via its C-terminus to the gp6 oligomer positioning gp15 subunits for oligomerization. Gp15 refolds its inner loops creating an intersubunit β-barrel that establishes different types of contacts with six gp16 subunits. Gp16 binding and oligomerization is accompanied by folding of helices that close the portal channel to keep the viral genome inside the capsid. This mechanism of assembly has broad functional and evolutionary implications for viruses of the prokaryotic tailed viruses-herpesviruses lineage.
Published: 2022

27. Laboratory evidence of magnetic reconnection hampered in obliquely interacting flux tubes

Author: Simon Bolaños, Andrey Sladkov, Roch Smets, Sophia N. Chen, Alain Grisollet, Evgeny Filippov, Jose-Luis Henares, Viorel Nastasa, Sergey Pikuz, Raphël Riquier, Maria Safronova, Alexandre Severin, Mikhail Starodubtsev, Julien Fuchs, Laboratoire pour l'utilisation des lasers intenses (LULI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Plasmas (LPP), Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École polytechnique (X)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Nizhny Novgorod State University, DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Horia Hulubei National Institute for Physics and Nuclear Engineering, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), and Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Multidisciplinary, [PHYS.PHYS.PHYS-PLASM-PH]Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Magnetic reconnection can occur when two plasmas, having anti-parallel components of the magnetic field, encounter each other. In the reconnection plane, the anti-parallel component of the field is annihilated and its energy released in the plasma. Here, we investigate through laboratory experiments the reconnection between two flux tubes that are not strictly anti-parallel. Compression of the anti-parallel component of the magnetic field is observed, as well as a decrease of the reconnection efficiency. Concomitantly, we observe delayed plasma heating and enhanced particle acceleration. Three-dimensional hybrid simulations support these observations and highlight the plasma heating inhibition and reconnection efficiency reduction for these obliquely oriented flux tubes.
Published: 2022

28. Towards the engineering of a photon-only two-stroke rotary molecular motor

Author: Michael Filatov, Marco Paolino, Robin Pierron, Andrea Cappelli, Gianluca Giorgi, Jérémie Léonard, Miquel Huix-Rotllant, Nicolas Ferré, Xuchun Yang, Danil Kaliakin, Alejandro Blanco-González, Massimo Olivucci, Kyungpook National University [Daegu] (KNU), Università degli Studi di Siena = University of Siena (UNISI), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bowling Green State University (BGSU), ANR-20-CE29-0021,PhotoMecha,Utiliser l'influence de l'environnement sur la photoréactivité, pour comprendre le mécanisme de photoisomérisation(2020), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-17-EURE-0024,QMAT,Quantum Science and Nanomaterials(2017), and ANR-11-LABX-0058,NIE,Nanostructures en Interaction avec leur Environnement(2011)
Subjects: [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Stroke, Photons, Multidisciplinary, Rotation, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Humans, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: The rational engineering of photoresponsive materials, e.g., light-driven molecular motors, is a challenging task. Here, we use structure-related design rules to prepare a prototype molecular rotary motor capable of completing an entire revolution using, exclusively, the sequential absorption of two photons; i.e., a photon-only two-stroke motor. The mechanism of rotation is then characterised using a combination of non-adiabatic dynamics simulations and transient absorption spectroscopy measurements. The results show that the rotor moiety rotates axially relative to the stator and produces, within a few picoseconds at ambient T, an intermediate with the same helicity as the starting structure. We discuss how such properties, that include a 0.25 quantum efficiency, can help overcome the operational limitations of the classical overcrowded alkene designs.
Published: 2022

29. The intervening domain is required for DNA-binding and functional identity of plant MADS transcription factors

Author: Lai, Xuelei, Vega-Léon, Rosario, Hugouvieux, Veronique, Blanc-Mathieu, Romain, van der Wal, Froukje, Lucas, Jérémy, Silva, Catarina S., Jourdain, Agnès, Muino, Jose M., Nanao, Max H., Immink, Richard, Kaufmann, Kerstin, Parcy, François, Smaczniak, Cezary, Zubieta, Chloe, Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), StructDev (StructDev), Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Humboldt University Of Berlin, Régulateurs du développement de la fleur (Flo_RE ), Wageningen University and Research [Wageningen] (WUR), European Synchroton Radiation Facility [Grenoble] (ESRF), ANR-16-CE92-0023,FLOPINET,Floral Pioneer Factors(2016), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), Humboldt-Universität zu Berlin, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, animal structures, Plant molecular biology, Science, Arabidopsis, MADS Domain Proteins, Flowers, 01 natural sciences, Article, AGAMOUS Protein, Arabidopsis, 500 Naturwissenschaften und Mathematik, 03 medical and health sciences, Gene Expression Regulation, Plant, Laboratorium voor Moleculaire Biologie, Life Science, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Protein Interaction Domains and Motifs, BIOS Plant Development Systems, X-ray crystallography, 030304 developmental biology, Homeodomain Proteins, 0303 health sciences, Arabidopsis Proteins, fungi, Plant morphogenesis, food and beverages, DNA-Binding Proteins, Phenotype, Laboratory of Molecular Biology, ddc:500, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Transcription Factors, 010606 plant biology & botany
Abstract: The MADS transcription factors (TF) are an ancient eukaryotic protein family. In plants, the family is divided into two main lineages. Here, we demonstrate that DNA binding in both lineages absolutely requires a short amino acid sequence C-terminal to the MADS domain (M domain) called the Intervening domain (I domain) that was previously defined only in type II lineage MADS. Structural elucidation of the MI domains from the floral regulator, SEPALLATA3 (SEP3), shows a conserved fold with the I domain acting to stabilise the M domain. Using the floral organ identity MADS TFs, SEP3, APETALA1 (AP1) and AGAMOUS (AG), domain swapping demonstrate that the I domain alters genome-wide DNA-binding specificity and dimerisation specificity. Introducing AG carrying the I domain of AP1 in the Arabidopsis ap1 mutant resulted in strong complementation and restoration of first and second whorl organs. Taken together, these data demonstrate that the I domain acts as an integral part of the DNA-binding domain and significantly contributes to the functional identity of the MADS TF., MADS transcription factors regulate multiple aspects of plant development. Here the authors show that the intervening I domain is conserved in both type I and type II plant MADS lineages and contributes to the functional identity of the protein by influencing both DNA binding activity and dimerisation specificity.
Published: 2021

30. Porous functionalized polymers enable generating and transporting hyperpolarized mixtures of metabolites

Author: James G. Kempf, Jonas Milani, Sami Jannin, Morgan Ceillier, Quentin Stern, Basile Vuichoud, Damien Montarnal, Marc Schnell, Dmitry Eshchenko, Samuel F. Cousin, Roberto Melzi, Théo El Daraï, Aurélien Bornet, Olivier Cala, Laurent Gremillard, Catalyse, Polymérisation, Procédés et Matériaux (CP2M), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de RMN à très hauts champs de Lyon (CRMN), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bruker BioSpin [Billerica, MA], Bruker Biospin, Bruker, Bruker BioSpin, Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Nitroxide mediated radical polymerization, Materials science, Science, General Physics and Astronomy, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, General Biochemistry, Genetics and Molecular Biology, Hyperpolarization (physics), Polarization (electrochemistry), Dissolution, chemistry.chemical_classification, Multidisciplinary, Aqueous solution, Relaxation (NMR), [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, Polymer, 021001 nanoscience & nanotechnology, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Chemical engineering, Spin diffusion, Polymer synthesis, 0210 nano-technology, Solution-state NMR
Abstract: Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g−1. Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P(13C) = 25% within 8 min, through the combination of 1H spin diffusion and 1H → 13C cross polarization. Solutions of 13C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances., Hyperpolarization by dissolution dynamic nuclear polarization has brought highly sensitive magnetic resonance to reality but there still remains severe limitations. Here the authors show an approach relying on the generation of hyperpolarizing polymers that bear a dual function.
Published: 2021

31. Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori

Author: Pernitzsch, Sandy, Alzheimer, Mona, Bremer, Belinda, Robbe-Saule, Marie, De Reuse, Hilde, Sharma, Cynthia, University of Würzburg, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Open Access funding enabled and organized by Projekt DEAL. This publication was supported by the Open Access Publication Fund of the University of Würzburg. The Sharma lab received financial support from the Deutsche Forschungsgemeinschaft (DFG) project Sh580/1-1, the Young Academy program of the Bavarian Academy of Sciences and Humanities (BAdW), and the Bavarian Research Network bayresq.net. The De Reuse’s lab was funded by the Agence National de la Recherche [ANR-12-BSV5-0025-Bactox1] and the Pasteur-Weizmann consortium 'The roles of noncoding RNAs in regulation of microbial life styles and virulence.', ANR-12-BSV5-0025,BacTox1,Rôle des systèmes toxine antitoxine de type I dans la persistence bactérienne(2012), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, and BLANC - Rôle des systèmes toxine antitoxine de type I dans la persistence bactérienne - - BacTox12012 - ANR-12-BSV5-0025 - BLANC - VALID
Subjects: Lipopolysaccharides, Bacterial immune evasion, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Salt Stress, Article, Helicobacter Infections, Mice, Bacterial Proteins, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bacterial genetics, Drug Resistance, Bacterial, Animals, ddc:610, Polymyxin B, Repetitive Sequences, Nucleic Acid, Helicobacter pylori, Stomach, Small RNAs, O Antigens, Gene Expression Regulation, Bacterial, RNA, Bacterial, RNA, Small Untranslated, Pathogens, 5' Untranslated Regions
Abstract: The small, regulatory RNA RepG (Regulator of polymeric G-repeats) regulates the expression of the chemotaxis receptor TlpB in Helicobacter pylori by targeting a variable G-repeat in the tlpB mRNA leader. Here, we show that RepG additionally controls lipopolysaccharide (LPS) phase variation by also modulating the expression of a gene (hp0102) that is co-transcribed with tlpB. The hp0102 gene encodes a glycosyltransferase required for LPS O-chain biosynthesis and in vivo colonization of the mouse stomach. The G-repeat length defines a gradual (rather than ON/OFF) control of LPS biosynthesis by RepG, and leads to gradual resistance to a membrane-targeting antibiotic. Thus, RepG-mediated modulation of LPS structure might impact host immune recognition and antibiotic sensitivity, thereby helping H. pylori to adapt and persist in the host., The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.
Published: 2021

32. Impact of an accelerated melting of Greenland on malaria distribution over Africa

Author: Guigone Camus, Gilles Ramstein, Cyril Caminade, Margaux Charra, Dimitri Defrance, Adrian M. Tompkins, Alizée Chemison, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Modélisation du climat (CLIM), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), University of Liverpool, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, 010504 meteorology & atmospheric sciences, Epidemiology, Rain, Science, Greenland, General Physics and Astronomy, Distribution (economics), Climate change, Mosquito Vectors, Global Warming, 01 natural sciences, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Malaria transmission, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles, parasitic diseases, Prevalence, medicine, Animals, Humans, Ice Cover, 0105 earth and related environmental sciences, Multidisciplinary, biology, business.industry, Global warming, General Chemistry, Models, Theoretical, medicine.disease, biology.organism_classification, Malaria, 3. Good health, 030104 developmental biology, Geography, 13. Climate action, Agriculture, Climatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology, business, Risk assessment, Climate-change impacts
Abstract: Studies about the impact of future climate change on diseases have mostly focused on standard Representative Concentration Pathway climate change scenarios. These scenarios do not account for the non-linear dynamics of the climate system. A rapid ice-sheet melting could occur, impacting climate and consequently societies. Here, we investigate the additional impact of a rapid ice-sheet melting of Greenland on climate and malaria transmission in Africa using several malaria models driven by Institute Pierre Simon Laplace climate simulations. Results reveal that our melting scenario could moderate the simulated increase in malaria risk over East Africa, due to cooling and drying effects, cause a largest decrease in malaria transmission risk over West Africa and drive malaria emergence in southern Africa associated with a significant southward shift of the African rain-belt. We argue that the effect of such ice-sheet melting should be investigated further in future public health and agriculture climate change risk assessments., Release of freshwater into the oceans as a result of ice sheet melting could impact the distribution of climate-sensitive diseases. Here, the authors show that a rapid ice sheet melting in Greenland could cause an emergence of malaria in Southern Africa whilst transmission risks in West Africa may decline.
Published: 2021

33. Climate pacing of millennial sea-level change variability in the central and western Mediterranean

Author: Vacchi, Matteo, Joyse, Kristen M., Kopp, Robert E., Marriner, Nick, Kaniewski, David, Rovere, Alessio, Dipartimento di Scienze della Terra [Pisa], University of Pisa - Università di Pisa, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), Théoriser et modéliser pour aménager (UMR 6049) (ThéMA), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Center for Marine Environmental Sciences [Bremen] (MARUM), Universität Bremen, Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Palaeoceanography, Physical oceanography, Science, Settore GEO/04 - Geografia Fisica e Geomorfologia, [SHS.GEO]Humanities and Social Sciences/Geography, sense organs, Palaeoclimate, skin and connective tissue diseases, Article, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography
Abstract: Future warming in the Mediterranean is expected to significantly exceed global values with unpredictable implications on the sea-level rise rates in the coming decades. Here, we apply an empirical-Bayesian spatio-temporal statistical model to a dataset of 401 sea-level index points from the central and western Mediterranean and reconstruct rates of sea-level change for the past 10,000 years. We demonstrate that the mean rates of Mediterranean industrial-era sea-level rise have been significantly faster than any other period since ~4000 years ago. We further highlight a previously unrecognized variability in Mediterranean sea-level change rates. In the Common Era, this variability correlates with the occurrence of major regional-scale cooling/warming episodes. Our data show a sea-level stabilization during the Late Antique Little Ice Age cold event, which interrupted a general rising trend of ~0.45 mm a−1 that characterized the warming episodes of the Common Era. By contrast, the Little Ice Age cold event had only minor regional effects on Mediterranean sea-level change rates., How sea-level in the western Mediterranean reacts to climate changes is not well known. Here, the authors present a regional reconstruction and show that temperatures influenced sea-level change rates during the Holocene, while recent sea-level rise is happening faster than during any other period of the last 4000 years.
Published: 2021

34. Predicting lapses of attention with sleep-like slow waves

Author: Naotsugu Tsuchiya, Teigane MacKay, Jennifer M. Windt, Angus C. Burns, Thomas Andrillon, Monash University [Melbourne], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), National Institute of Information and Communications Technology [Tokyo, Japan] (NICT), Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Consciousness, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Science, General Physics and Astronomy, Electroencephalography, Models, Psychological, Sleep, Slow-Wave, 050105 experimental psychology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Neural activity, 0302 clinical medicine, Mind-wandering, Task Performance and Analysis, medicine, Humans, 0501 psychology and cognitive sciences, Attention, Wakefulness, media_common, Behavior, Multidisciplinary, medicine.diagnostic_test, Transition (fiction), 05 social sciences, fungi, Brain, General Chemistry, [SDV] Life Sciences [q-bio], Cognitive control, Female, Sleep (system call), Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants performing a task. Random interruptions prompted participants to indicate their mental states as task-focused, mind-wandering or mind-blanking. Using high-density electroencephalography, we report here that spatially and temporally localized slow waves, a pattern of neural activity characteristic of the transition toward sleep, accompany behavioural markers of lapses and preceded reports of mind wandering and mind blanking. The location of slow waves could distinguish between sluggish and impulsive behaviours, and between mind wandering and mind blanking. Our results suggest attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain., Attentional lapses occur in many forms such as mind-wandering or mindblanking. Here the authors show different types of attentional lapse are accompanied by slow waves, neural activity that is characteristic of transitions into sleep.
Published: 2021

35. BRN2 is a non-canonical melanoma tumor-suppressor

Author: Pierre Sohier, Luis Sánchez-del-Campo, Nisamanee Charoenchon, Colin Kenny, Madeleine Le Coz, Colin R. Goding, Lionel Larue, Véronique Delmas, Valérie Petit, Alain Sarasin, Eiríkur Steingrímsson, Zackie Aktary, Jérémy H. Raymond, Dies Meijer, Franck Gesbert, Michael Hamm, Irwin Davidson, Robert A. Cornell, Laura Mosteo, Florian Rambow, Alfonso Bellacosa, Göran Jönsson, Marie Pouteaux, Martin Lauss, Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Carver College of Medicine [Iowa City], University of Iowa [Iowa City], Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Mahidol University [Bangkok], Fox Chase Cancer Center, University of Oxford [Oxford], Lund University [Lund], University of Edinburgh, University of Iceland [Reykjavik], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation, radiobiologie et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Carver College of Medicine, University of Iowa, University of Oxford, and delmas, veronique
Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Skin Neoplasms, Carcinogenesis, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Haploinsufficiency, Cohort Studies, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, CDKN2A, Genes, Tumor Suppressor, RNA, Small Interfering, Melanoma, Multidisciplinary, biology, Microphthalmia-associated transcription factor, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Mechanisms of disease, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Disease Progression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Proto-Oncogene Proteins B-raf, Chromatin Immunoprecipitation, DNA Copy Number Variations, Science, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, PTEN, Transcription factor, neoplasms, Cell Proliferation, Homeodomain Proteins, Microphthalmia-Associated Transcription Factor, POU domain, PTEN Phosphohydrolase, General Chemistry, Microarray Analysis, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Mutation, POU Domain Factors, biology.protein, Cancer research, Gene expression
Abstract: While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600E PtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression., The transcription factor BRN2 regulates melanoma migration and invasion, but its role during melanoma initiation is unclear. Here the authors show that BRN2 is a haplo-insufficient tumour suppressor that positively regulates PTEN expression and in the context of BRAF mutation and heterozygous PTEN, BRN2 loss promotes melanoma initiation and progression.
Published: 2021

36. Process-oriented analysis of dominant sources of uncertainty in the land carbon sink

Author: O'Sullivan, Michael, Friedlingstein, Pierre, Sitch, Stephen, Anthoni, Peter, Arneth, Almut, Arora, Vivek K, Bastrikov, Vladislav, Delire, Christine, Goll, Daniel S, Jain, Atul, Kato, Etsushi, Kennedy, Daniel, Knauer, Jürgen, Lienert, Sebastian, Lombardozzi, Danica, McGuire, Patrick C, Melton, Joe R, Nabel, Julia E M S, Pongratz, Julia, Poulter, Benjamin, Séférian, Roland, Tian, Hanqin, Vuichard, Nicolas, Walker, Anthony P, Yuan, Wenping, Yue, Xu, Zaehle, Sönke, Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre national de recherches météorologiques (CNRM), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Modélisation des Surfaces et Interfaces Continentales (MOSAIC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and M.O.S., P.F. and S.S. have received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 821003 (project 4 C).
Subjects: [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Carbon Sequestration, Multidisciplinary, 530 Physics, Uncertainty, General Physics and Astronomy, General Chemistry, Carbon Dioxide, Plants, Carbon, General Biochemistry, Genetics and Molecular Biology, Earth sciences, Soil, ddc:550, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, Ecosystem
Abstract: The observed global net land carbon sink is captured by current land models. All models agree that atmospheric CO2 and nitrogen deposition driven gains in carbon stocks are partially offset by climate and land-use and land-cover change (LULCC) losses. However, there is a lack of consensus in the partitioning of the sink between vegetation and soil, where models do not even agree on the direction of change in carbon stocks over the past 60 years. This uncertainty is driven by plant productivity, allocation, and turnover response to atmospheric CO2 (and to a smaller extent to LULCC), and the response of soil to LULCC (and to a lesser extent climate). Overall, differences in turnover explain ~70% of model spread in both vegetation and soil carbon changes. Further analysis of internal plant and soil (individual pools) cycling is needed to reduce uncertainty in the controlling processes behind the global land carbon sink.
Published: 2022

37. Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

Author: Thomas Obadia, Gladys Gutierrez-Bugallo, Veasna Duong, Ana I. Nuñez, Rosilainy S. Fernandes, Basile Kamgang, Liza Hery, Yann Gomard, Sandra R. Abbo, Davy Jiolle, Uros Glavinic, Myrielle Dupont-Rouzeyrol, Célestine M. Atyame, Nicolas Pocquet, Sébastien Boyer, Catherine Dauga, Marie Vazeille, André Yébakima, Michael T. White, Constantianus J. M. Koenraadt, Patrick Mavingui, Anubis Vega-Rua, Eva Veronesi, Gorben P. Pijlman, Christophe Paupy, Núria Busquets, Ricardo Lourenço-de-Oliveira, Xavier De Lamballerie, Anna-Bella Failloux, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics, Pedro Kouri Institute of Tropical Medicine, Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Cambodge, Centre de Recerca en Sanitat Animal [UAB, Spain] (CReSA), Universitat Autònoma de Barcelona (UAB)-Institut de Recerca i Tecnologia Agroalimentàries = Institute of Agrifood Research and Technology (IRTA), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre for Research in Infectious Diseases [Yaoundé] (CRID), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Wageningen University and Research [Wageningen] (WUR), Universität Zürich [Zürich] = University of Zurich (UZH), Institut Pasteur de Nouvelle-Calédonie, Entomologie médicale [Nouméa, Nouvelle-Calédonie] (URE-EM), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, VECCOTRA, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tis study was supported by the European Union’s Horizon 2020 research and innovation program under ZIKAlliance grant agreement no. 734548., European Project: 734548,ZIKAlliance(2016), Fundação Oswaldo Cruz (FIOCRUZ), Obadia, Thomas, A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID, University of Zurich, Failloux, Anna-Bella, Producció Animal, and Sanitat Animal
Subjects: 10078 Institute of Parasitology, Laboratory of Virology, General Physics and Astronomy, 610 Medicine & health, 1600 General Chemistry, Genetics and Molecular Biology, MESH: Zika Virus, Mosquito Vectors, Virus-host interactions, General Biochemistry, Genetics and Molecular Biology, Disease Outbreaks, Laboratorium voor Virologie, MESH: Zika Virus Infection, 1300 General Biochemistry, Genetics and Molecular Biology, Aedes, 600 Technology, Life Science, Animals, Humans, MESH: Animals, Laboratory of Entomology, MESH: Disease Outbreaks, 1000 Multidisciplinary, MESH: Humans, Multidisciplinary, Zika Virus Infection, Virus–host interactions, MESH: Infant, Newborn, Infant, Newborn, Zika Virus, MESH: Aedes, General Chemistry, PE&RC, Laboratorium voor Entomologie, 3100 General Physics and Astronomy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, General Biochemistry, 570 Life sciences, biology, MESH: Mosquito Vectors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Entomology
Abstract: First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika. Zika virus (ZIKV), the causative agent of virus-induced brain damage in newborns, is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus. Here, Obadia et al. characterize ZIKV vector competence of 50 mosquito populations from six species collected in 12 different countries to inform about epidemic risk. They find that African ZIKV strain shows higher transmission efficiency compared to American and Asian ZIKV strains and that Ae. aegypti mosquitoes have highest susceptibility to infections, while Culex mosquitoes are largely non-susceptible.
Published: 2022

38. Fundamental investigations on the sodium-ion transport properties of mixed polyanion solid-state battery electrolytes

Author: Zeyu Deng, Tara P. Mishra, Eunike Mahayoni, Qianli Ma, Aaron Jue Kang Tieu, Olivier Guillon, Jean-Noël Chotard, Vincent Seznec, Anthony K. Cheetham, Christian Masquelier, Gopalakrishnan Sai Gautam, Pieremanuele Canepa, Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, Laboratoire réactivité et chimie des solides - UMR CNRS 7314 (LRCS), Université de Picardie Jules Verne (UPJV)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Réseau sur le stockage électrochimique de l'énergie (RS2E), Aix Marseille Université (AMU)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Collège de France (CdF (institution))-Université de Picardie Jules Verne (UPJV)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA)-Nantes Université (Nantes Univ)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Department of Materials Science and Metallurgy [Cambridge University] (DMSM), University of Cambridge [UK] (CAM), Department of Materials Engineering, Indian Institute of Science [Bangalore] (IISc Bangalore), Deparment of Chemical and Biomolecular Engineering, National University of Singapore (NUS), Department of Materials Science and Engineering, Max Planck Institute for Intelligent Systems [Tübingen], and Max-Planck-Gesellschaft
Subjects: Multidisciplinary, General Physics and Astronomy, [CHIM.MATE]Chemical Sciences/Material chemistry, ddc:500, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Lithium and sodium (Na) mixed polyanion solid electrolytes for all-solid-state batteries display some of the highest ionic conductivities reported to date. However, the effect of polyanion mixing on the ion-transport properties is still not fully understood. Here, we focus on Na1+xZr2SixP3−xO12 (0 ≤ x ≤ 3) NASICON electrolyte to elucidate the role of polyanion mixing on the Na-ion transport properties. Although NASICON is a widely investigated system, transport properties derived from experiments or theory vary by orders of magnitude. We use more than 2000 distinct ab initio-based kinetic Monte Carlo simulations to map the compositional space of NASICON over various time ranges, spatial resolutions and temperatures. Via electrochemical impedance spectroscopy measurements on samples with different sodium content, we find that the highest ionic conductivity (i.e., about 0.165 S cm–1 at 473 K) is experimentally achieved in Na3.4Zr2Si2.4P0.6O12, in line with simulations (i.e., about 0.170 S cm–1 at 473 K). The theoretical studies indicate that doped NASICON compounds (especially those with a silicon content x ≥ 2.4) can improve the Na-ion mobility compared to undoped NASICON compositions.
Published: 2022

39. De novo determination of mosquitocidal Cry11Aa and Cry11Ba structures from naturally-occurring nanocrystals

Author: Guillaume Tetreau, Michael R. Sawaya, Elke De Zitter, Elena A. Andreeva, Anne-Sophie Banneville, Natalie A. Schibrowsky, Nicolas Coquelle, Aaron S. Brewster, Marie Luise Grünbein, Gabriela Nass Kovacs, Mark S. Hunter, Marco Kloos, Raymond G. Sierra, Giorgio Schiro, Pei Qiao, Myriam Stricker, Dennis Bideshi, Iris D. Young, Ninon Zala, Sylvain Engilberge, Alexander Gorel, Luca Signor, Jean-Marie Teulon, Mario Hilpert, Lutz Foucar, Johan Bielecki, Richard Bean, Raphael de Wijn, Tokushi Sato, Henry Kirkwood, Romain Letrun, Alexander Batyuk, Irina Snigireva, Daphna Fenel, Robin Schubert, Ethan J. Canfield, Mario M. Alba, Frédéric Laporte, Laurence Després, Maria Bacia, Amandine Roux, Christian Chapelle, François Riobé, Olivier Maury, Wai Li Ling, Sébastien Boutet, Adrian Mancuso, Irina Gutsche, Eric Girard, Thomas R. M. Barends, Jean-Luc Pellequer, Hyun-Woo Park, Arthur D. Laganowsky, Jose Rodriguez, Manfred Burghammer, Robert L. Shoeman, R. Bruce Doak, Martin Weik, Nicholas K. Sauter, Brian Federici, Duilio Cascio, Ilme Schlichting, Jacques-Philippe Colletier, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), UCLA/DOE Institute for Genomics and Proteomics, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Groupe Dynamique et Cinétique des processus moléculaires (IBS-DYNAMOP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Max-Planck-Institut für Medizinische Forschung, Max-Planck-Gesellschaft, Max Planck Institute for Medical Research [Heidelberg], Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory (SLAC), Stanford University-Stanford University, California Baptist University (CBU), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), European Synchroton Radiation Facility [Grenoble] (ESRF), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de Chimie - UMR5182 (LC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Stanford University, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and ANR-17-CE11-0018,X-in-vivo,Cristallisation in vivo: une nouvelle stratégie pour étudier la structure et la dynamique des protéines dans les lasers à électrons libres et les synchrotrons.(2017)
Subjects: Mosquito Control, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Bacillus thuringiensis, General Physics and Astronomy, General Chemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, General Biochemistry, Genetics and Molecular Biology, Endotoxins, Hemolysin Proteins, Bacterial Proteins, Larva, [CHIM.CRIS]Chemical Sciences/Cristallography, Animals, Nanoparticles, [CHIM]Chemical Sciences
Abstract: Cry11Aa and Cry11Ba are the two most potent toxins produced by mosquitocidal Bacillus thuringiensis subsp. israelensis and jegathesan, respectively. The toxins naturally crystallize within the host; however, the crystals are too small for structure determination at synchrotron sources. Therefore, we applied serial femtosecond crystallography at X-ray free electron lasers to in vivo-grown nanocrystals of these toxins. The structure of Cry11Aa was determined de novo using the single-wavelength anomalous dispersion method, which in turn enabled the determination of the Cry11Ba structure by molecular replacement. The two structures reveal a new pattern for in vivo crystallization of Cry toxins, whereby each of their three domains packs with a symmetrically identical domain, and a cleavable crystal packing motif is located within the protoxin rather than at the termini. The diversity of in vivo crystallization patterns suggests explanations for their varied levels of toxicity and rational approaches to improve these toxins for mosquito control.
Published: 2022

40. A modular spring-loaded actuator for mechanical activation of membrane proteins

Author: A. Mills, N. Aissaoui, D. Maurel, J. Elezgaray, F. Morvan, J. J. Vasseur, E. Margeat, R. B. Quast, J. Lai Kee-Him, N. Saint, C. Benistant, A. Nord, F. Pedaci, G. Bellot, MORNET, Dominique, Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génomique Fonctionnelle (IGF), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), and Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp)
Subjects: [SDV] Life Sciences [q-bio], Multidisciplinary, Focal Adhesion Protein-Tyrosine Kinases, [SDV]Life Sciences [q-bio], Membrane Proteins, General Physics and Astronomy, DNA, Stress, Mechanical, General Chemistry, Mechanoreceptors, Mechanotransduction, Cellular, General Biochemistry, Genetics and Molecular Biology
Abstract: How cells respond to mechanical forces by converting them into biological signals underlie crucial cellular processes. Our understanding of mechanotransduction has been hindered by technical barriers, including limitations in our ability to effectively apply low range piconewton forces to specific mechanoreceptors on cell membranes without laborious and repetitive trials. To overcome these challenges we introduce the Nano-winch, a robust, easily assembled, programmable DNA origami-based molecular actuator. The Nano-winch is designed to manipulate multiple mechanoreceptors in parallel by exerting fine-tuned, low- piconewton forces in autonomous and remotely activated modes via adjustable single- and double-stranded DNA linkages, respectively. Nano-winches in autonomous mode can land and operate on the cell surface. Targeting the device to integrin stimulated detectable downstream phosphorylation of focal adhesion kinase, an indication that Nano-winches can be applied to study cellular mechanical processes. Remote activation mode allowed finer extension control and greater force exertion. We united remotely activated Nano-winches with single-channel bilayer experiments to directly observe the opening of a channel by mechanical force in the force responsive gated channel protein, BtuB. This customizable origami provides an instrument-free approach that can be applied to control and explore a diversity of mechanotransduction circuits on living cells.
Published: 2022

41. Tropical forests as drivers of lake carbon burial

Author: Leonardo Amora-Nogueira, Christian J. Sanders, Alex Enrich-Prast, Luciana Silva Monteiro Sanders, Rodrigo Coutinho Abuchacra, Patricia F. Moreira-Turcq, Renato Campello Cordeiro, Vincent Gauci, Luciane Silva Moreira, Fausto Machado-Silva, Renata Libonati, Thairiny Fonseca, Cristiane Nunes Francisco, Humberto Marotta, Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche pour le Développement (IRD)
Subjects: Carbon Sequestration, Geologic Sediments, Tropical Climate, Multidisciplinary, Naturgeografi, General Physics and Astronomy, General Chemistry, Forests, Carbon, General Biochemistry, Genetics and Molecular Biology, Lakes, Physical Geography, [SDE]Environmental Sciences, Ecosystem
Abstract: A significant proportion of carbon (C) captured by terrestrial primary production is buried in lacustrine ecosystems, which have been substantially affected by anthropogenic activities globally. However, there is a scarcity of sedimentary organic carbon (OC) accumulation information for lakes surrounded by highly productive rainforests at warm tropical latitudes, or in response to land cover and climate change. Here, we combine new data from intensive campaigns spanning 13 lakes across remote Amazonian regions with a broad literature compilation, to produce the first spatially-weighted global analysis of recent OC burial in lakes (over ~50-100-years) that integrates both biome type and forest cover. We find that humid tropical forest lake sediments are a disproportionately important global OC sink of ~80 Tg C yr−1 with implications for climate change. Further, we demonstrate that temperature and forest conservation are key factors in maintaining massive organic carbon pools in tropical lacustrine sediments.
Published: 2022

42. The effect of COVID certificates on vaccine uptake, health outcomes, and the economy

Author: Miquel Oliu-Barton, Bary S. R. Pradelski, Nicolas Woloszko, Lionel Guetta-Jeanrenaud, Philippe Aghion, Patrick Artus, Arnaud Fontanet, Philippe Martin, Guntram B. Wolff, CEntre de REcherches en MAthématiques de la DEcision (CEREMADE), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), CNRS-périodiques (CP), Centre National de la Recherche Scientifique (CNRS), Organisation de Coopération et de Développement Economiques = Organisation for Economic Co-operation and Development (OCDE), Auteur indépendant, Institut Européen d'administration des Affaires (INSEAD), Collège de France - Chaire Economie des institutions, de l'innovation et de la croissance, Collège de France (CdF (institution)), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Jourdan Sciences Economiques (PJSE), Natixis, Institut Pasteur [Paris] (IP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Département d'économie (Sciences Po) (ECON), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Center for Economic Policy Research (CEPR), CEPR, Solvay Brussels School of Economics and Management [Brussels] (ULB), Université libre de Bruxelles (ULB), This work has been partially supported by Bruegel, French National Research Agency (ANR) through grant ANR-19-CE48-0018-01, and University Paris Dauphine - PSL. All errors are ours., and ANR-19-CE48-0018,ALIAS,Apprentissage adaptatif multi-agent(2019)
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Vaccines, Multidisciplinary, Economics, Epidemiology, SARS-CoV-2, COVID-19, General Physics and Astronomy, General Chemistry, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Health policy, General Biochemistry, Genetics and Molecular Biology, Italy, Germany, Communicable Disease Control, Outcome Assessment, Health Care, Humans, France, Pandemics
Abstract: In the COVID-19 pandemic, governments have, among other measures,1,2 mandated the use of COVID certificates to prove vaccination, recovery, or a recent negative test, and have required them to access shops, restaurants, schools, universities, or workplaces.3 While arguments for and against COVID certificates have focused on reducing transmission and ethical concerns,4,5 the incentive effect of COVID certificates on vaccine uptake, health outcomes, and the economy has not yet been investigated. To estimate this effect, we construct counterfactuals based on innovation diffusion theory6 for France, Germany, and Italy. We estimate that the announcement of COVID certificates during summer 2021 led to increased vaccine uptake in France of 13.0 (95% CI 9.7–14.9) percentage points (p.p.) of the total population up to the end of the year, in Germany 6.2 (2.6–6.9) p.p., and in Italy 9.7 (5.4–12.3) p.p. Further, this averted an additional 3,979 (3,453–4,298) deaths in France, 1,133 (-312–1,358) in Germany, and 1,331 (502–1,794) in Italy; and prevented gross domestic product (GDP) losses of €6.0 (5.9–6.1) billion in France, €1.4 (1.3–1.5) billion in Germany, and €2.1 (2.0–2.2) billion in Italy. Notably, the application of COVID certificates substantially reduced the pressure on intensive care units (ICUs) and, in France, averted occupancy levels being exceeded where prior lockdowns were instated. Varying government communication efforts and restrictions associated with COVID certificates may explain country differences, such as the smaller effect in Germany. Overall, our findings are more sizeable than predicted.7 This analysis may help inform decisions about when and how to employ COVID certificates to increase vaccine uptake and thus avoid stringent interventions, such as closures, curfews, and lockdowns, with major social and economic consequences.
Published: 2022

43. Deep learning from phylogenies to uncover the epidemiological dynamics of outbreaks

Author: Voznica, J., Zhukova, A., Boskova, V., Saulnier, E., Lemoine, F., Moslonka-Lefebvre, M., Gascuel, O., Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Vienna [Vienna], Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), J.V. is supported by Ecole Normale Supérieure Paris-Saclay and by ED Frontières de l’Innovation en Recherche et Education, Programme Bettencourt. V.B. would like to thank Swiss National Science Foundation for funding (Early PostDoc mobility grant P2EZP3_184543). O.G. is supported by PRAIRIE (ANR-19-P3IA-0001)., and ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019)
Subjects: Male, tree simulation and representation, Multidisciplinary, Statistical methods, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], HIV, General Physics and Astronomy, Bayes Theorem, General Chemistry, phylodynamics, molecular epidemiology, General Biochemistry, Genetics and Molecular Biology, Disease Outbreaks, Deep Learning, Viral infection, Machine learning, Humans, Computer Simulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Phylogeny
Abstract: Widely applicable, accurate and fast inference methods in phylodynamics are needed to fully profit from the richness of genetic data in uncovering the dynamics of epidemics. Standard methods, including maximum-likelihood and Bayesian approaches, generally rely on complex mathematical formulae and approximations, and do not scale with dataset size. We develop a likelihood-free, simulation-based approach, which combines deep learning with (1) a large set of summary statistics measured on phylogenies or (2) a complete and compact representation of trees, which avoids potential limitations of summary statistics and applies to any phylodynamics model. Our method enables both model selection and estimation of epidemiological parameters from very large phylogenies. We demonstrate its speed and accuracy on simulated data, where it performs better than the state-of-the-art methods. To illustrate its applicability, we assess the dynamics induced by superspreading individuals in an HIV dataset of men-having-sex-with-men in Zurich. Our tool PhyloDeep is available on github.com/evolbioinfo/phylodeep.
Published: 2022

44. Photochemical Synthesis of Transition Metal-Stabilized Uranium(VI) Nitride Complexes

Author: Xiaoqing Xin, Iskander Douair, Thayalan Rajeshkumar, Yue Zhao, Shuao Wang, Laurent Maron, Congqing Zhu, Nanjing University (NJU), Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Fédération de recherche « Matière et interactions » (FeRMI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Soochow University
Subjects: Multidisciplinary, MAGNETIC COMMUNICATION, AZIDE, CLEAVAGE, H BOND ACTIVATION, General Physics and Astronomy, TRANSIENT, General Chemistry, REACTIVITY, General Biochemistry, Genetics and Molecular Biology, REDUCTION, CHEMISTRY, FUNCTIONALIZATION, [CHIM]Chemical Sciences, PHOTOLYSIS
Abstract: Uranium nitrides play important roles in dinitrogen activation and functionalization and in chemistry for nuclear fuels, but the synthesis and isolation of the highly reactive uranium(VI) nitrides remains challenging. Here, we report an example of transition metal (TM) stabilized U(VI) nitride complexes, which are generated by the photolysis of azide-bridged U(IV)-TM (TM = Rh, Ir) precursors. The U(V) nitride intermediates with bridged azide ligands are isolated successfully by careful control of the irradiation time, suggesting that the photolysis of azide-bridged U(IV)-TM precursors is a stepwise process. The presence of two U(VI) nitrides stabilized by three TMs is clearly demonstrated by an X-ray crystallographic study. These TM stabilized U(V) nitride intermediates and U(VI) nitride products exhibit excellent stability both in the solid-state and in THF solution under ambient light. Density functional theory calculations show that the photolysis necessary to break the N-N bond of the azide ligands implies excitation from uranium f-orbital to the lowest unoccupied molecular orbital (LUMO), as suggested by the strong antibonding N-(N2) character present in the latter.
Published: 2022

45. Defect-induced monopole injection and manipulation in artificial spin ice

Author: Robert Puttock, Ingrid M. Andersen, Christophe Gatel, Bumsu Park, Mark C. Rosamond, Etienne Snoeck, Olga Kazakova, National Physical Laboratory [Teddington] (NPL), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Interférométrie, In situ et Instrumentation pour la Microscopie Electronique (CEMES-I3EM), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: Multidisciplinary, High Energy Physics::Lattice, [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], [CHIM.CRIS]Chemical Sciences/Cristallography, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], General Physics and Astronomy, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Lithographically defined arrays of nanomagnets are well placed for application in areas such as probabilistic computing or reconfigurable magnonics due to their emergent collective dynamics and writable magnetic order. Among them are artificial spin ice (ASI), which are arrays of binary in-plane macrospins exhibiting geometric frustration at the vertex interfaces. Macrospin flips in the arrays create topologically protected magnetic charges, or emergent monopoles, which are bound to an antimonopole to conserve charge. In the absence of controllable pinning, it is difficult to manipulate individual monopoles in the array without also influencing other monopole excitations or the counter-monopole charge. Here, we tailor the local magnetic order of a classic ASI lattice by introducing a ferromagnetic defect with shape anisotropy into the array. This creates monopole injection sites at nucleation fields below the critical lattice switching field. Once formed, the high energy monopoles are fixed to the defect site and may controllably propagate through the lattice under stimulation. Defect programing of bound monopoles within the array allows fine control of the pathways of inverted macrospins. Such control is a necessary prerequisite for the realization of functional devices, e. g. reconfigurable waveguide in nanomagnonic applications.
Published: 2022

46. Stability of high-temperature salty ice suggests electrolyte permeability in water-rich exoplanet icy mantles

Author: Jean-Alexis Hernandez, Razvan Caracas, Stéphane Labrosse, Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP (UMR_7154)), and Institut national des sciences de l'Univers (INSU - CNRS)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Multidisciplinary, [SDU]Sciences of the Universe [physics], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Electrolytes play an important role in the internal structure and dynamics of water-rich satellites and potentially water-rich exoplanets. However, in planets, the presence of a large high-pressure ice mantle is thought to hinder the exchange and transport of electrolytes between various liquid and solid deep layers. Here we show, using first-principles simulations, that up to 2.5 wt% NaCl can be dissolved in dense water ice at interior conditions of water-rich super-Earths and mini-Neptunes. The salt impurities enhance the diffusion of H atoms, extending the stability field of recently discovered superionic ice, and push towards higher pressures the transition to the stiffer ice X phase. Scaling laws for thermo-compositional convection show that salts entering the high pressure ice layer can be readily transported across. These findings suggest that the high-pressure ice mantle of water-rich exoplanets is permeable to the convective transport of electrolytes between the inner rocky core and the outer liquid layer.
Published: 2022

47. Disease modeling by efficient genome editing using a near PAM-less base editor in vivo

Author: Marion Rosello, Malo Serafini, Luca Mignani, Dario Finazzi, Carine Giovannangeli, Marina C. Mione, Jean-Paul Concordet, Filippo Del Bene, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Brescia, Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), and University of Trento [Trento]
Subjects: Genome editing, Crispr/Cas9, disease modeling, zebrafish, Multidisciplinary, [SDV]Life Sciences [q-bio], disease modeling, General Physics and Astronomy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Crispr/Cas9, General Chemistry, zebrafish, General Biochemistry, Genetics and Molecular Biology, Genome editing
Abstract: Base Editors are emerging as an innovative technology to introduce point mutations in complex genomes. So far, the requirement of an NGG Protospacer Adjacent Motif (PAM) at a suitable position often limits the base editing possibility to model human pathological mutations in animals. Here we show that, using the CBE4max-SpRY variant recognizing nearly all PAM sequences, we could introduce point mutations for the first time in an animal model with high efficiency, thus drastically increasing the base editing possibilities. With this near PAM-less base editor we could simultaneously mutate several genes and we developed a co-selection method to identify the most edited embryos based on a simple visual screening. Finally, we apply our method to create a zebrafish model for melanoma predisposition based on the simultaneous base editing of multiple genes. Altogether, our results considerably expand the Base Editor application to introduce human disease-causing mutations in zebrafish.
Published: 2022

48. Altered predictive control during memory suppression in PTSD

Author: Giovanni Leone, Charlotte Postel, Alison Mary, Florence Fraisse, Thomas Vallée, Fausto Viader, Vincent de La Sayette, Denis Peschanski, Jaques Dayan, Francis Eustache, Pierre Gagnepain, Université de Caen Normandie (UNICAEN), Normandie Université (NU), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Centre européen de sociologie et de science politique (CESSP), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Université de Rennes (UR), ANR-16-EQPX-0003,Matrice - 13 novembre,Matrice - 13 novembre(2016), Peschanski, Denis, Matrice - 13 novembre - - Matrice - 13 novembre2016 - ANR-16-EQPX-0003 - EQPX - VALID, Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Matrice - 13 novembre [En savoir plus]Matrice - 13 novembre - ANR-16-EQPX-0003EQPX - 2016, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre Hospitalier Guillaume Régnier [Rennes], French Commissariat-General for Investment (CGI) via the National Research Agency (ANR), Program d'investissement pour l'Avenir (PIA), CNRS, INSERM, Normandy Region and Normandy University, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and École des hautes études en sciences sociales (EHESS)
Subjects: Stress Disorders, Post-Traumatic, Paris, Multidisciplinary, [SDV]Life Sciences [q-bio], [SHS.HIST] Humanities and Social Sciences/History, Brain, Humans, General Physics and Astronomy, General Chemistry, Anxiety, [SHS.HIST]Humanities and Social Sciences/History, Hippocampus, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; It remains unclear how predictions of future threat affect memory recall, specifically in the case of post-traumatic stress disorder (PTSD). Here, the authors combined computational modeling and brain connectivity analyses to show that individuals with PTSD have exaggerated predictive control and reduced reactive control in a memory suppression task. Aberrant predictions of future threat lead to maladaptive avoidance in individuals with post-traumatic stress disorder (PTSD). How this disruption in prediction influences the control of memory states orchestrated by the dorsolateral prefrontal cortex is unknown. We combined computational modeling and brain connectivity analyses to reveal how individuals exposed and nonexposed to the 2015 Paris terrorist attacks formed and controlled beliefs about future intrusive re-experiencing implemented in the laboratory during a memory suppression task. Exposed individuals with PTSD used beliefs excessively to control hippocampal activity during the task. When this predictive control failed, the prediction-error associated with unwanted intrusions was poorly downregulated by reactive mechanisms. This imbalance was linked to higher severity of avoidance symptoms, but not to general disturbances such as anxiety or negative affect. Conversely, trauma-exposed participants without PTSD and nonexposed individuals were able to optimally balance predictive and reactive control during the memory suppression task. These findings highlight a potential pathological mechanism occurring in individuals with PTSD rooted in the relationship between the brain's predictive and control mechanisms.
Published: 2022

49. Neonatal gene therapy achieves sustained disease rescue of maple syrup urine disease in mice

Author: Clément Pontoizeau, Marcelo Simon-Sola, Clovis Gaborit, Vincent Nguyen, Irina Rotaru, Nolan Tual, Pasqualina Colella, Muriel Girard, Maria-Grazia Biferi, Jean-Baptiste Arnoux, Agnès Rötig, Chris Ottolenghi, Pascale de Lonlay, Federico Mingozzi, Marina Cavazzana, Manuel Schiff, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Généthon, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Cappella, Marisa
Subjects: [SDV] Life Sciences [q-bio], Mice, Phenotype, Multidisciplinary, Maple Syrup Urine Disease, [SDV]Life Sciences [q-bio], Animals, General Physics and Astronomy, Genetic Therapy, General Chemistry, Amino Acids, Branched-Chain, General Biochemistry, Genetics and Molecular Biology, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Abstract: Maple syrup urine disease (MSUD) is a rare recessively inherited metabolic disorder causing accumulation of branched chain amino acids leading to neonatal death, if untreated. Treatment for MSUD represents an unmet need because the current treatment with life-long low-protein diet is challenging to maintain, and despite treatment the risk of acute decompensations and neuropsychiatric symptoms remains. Here, based on significant liver contribution to the catabolism of the branched chain amino acid leucine, we develop a liver-directed adeno-associated virus (AAV8) gene therapy for MSUD. We establish and characterize the Bckdha (branched chain keto acid dehydrogenase a)−/− mouse that exhibits a lethal neonatal phenotype mimicking human MSUD. Animals were treated at P0 with intravenous human BCKDHA AAV8 vectors under the control of either a ubiquitous or a liver-specific promoter. BCKDHA gene transfer rescued the lethal phenotype. While the use of a ubiquitous promoter fully and sustainably rescued the disease (long-term survival, normal phenotype and correction of biochemical abnormalities), liver-specific expression of BCKDHA led to partial, though sustained rescue. Here we show efficacy of gene therapy for MSUD demonstrating its potential for clinical translation.
Published: 2022

50. Structural basis for allosteric regulation of Human Topoisomerase IIα

Author: Robert Drillien, Léa Haas, Arnaud Vanden Broeck, Christophe Lotz, Valérie Lamour, Claire Bedez, Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), univOAK, Archive ouverte, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Gene isoform, Models, Molecular, Science, Allosteric regulation, General Physics and Astronomy, Cleavage (embryo), DNA-binding protein, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Allosteric Regulation, Transcription (biology), Catalytic Domain, DNA-binding proteins, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Poly-ADP-Ribose Binding Proteins, Multidisciplinary, biology, Mesocricetus, Topoisomerase, Cryoelectron Microscopy, DNA replication, General Chemistry, DNA, Recombinant Proteins, Cell biology, Enzymes, 030104 developmental biology, DNA Topoisomerases, Type II, Nucleoproteins, chemistry, Enzyme mechanisms, biology.protein, Protein Processing, Post-Translational, 030217 neurology & neurosurgery
Abstract: The human type IIA topoisomerases (Top2) are essential enzymes that regulate DNA topology and chromosome organization. The Topo IIα isoform is a prime target for antineoplastic compounds used in cancer therapy that form ternary cleavage complexes with the DNA. Despite extensive studies, structural information on this large dimeric assembly is limited to the catalytic domains, hindering the exploration of allosteric mechanism governing the enzyme activities and the contribution of its non-conserved C-terminal domain (CTD). Herein we present cryo-EM structures of the entire human Topo IIα nucleoprotein complex in different conformations solved at subnanometer resolutions (3.6–7.4 Å). Our data unveils the molecular determinants that fine tune the allosteric connections between the ATPase domain and the DNA binding/cleavage domain. Strikingly, the reconstruction of the DNA-binding/cleavage domain uncovers a linker leading to the CTD, which plays a critical role in modulating the enzyme’s activities and opens perspective for the analysis of post-translational modifications., Type 2 DNA topoisomerases (Top2) regulates DNA topology during DNA replication, transcription, and chromosome segregation. Here the authors describe a complete structure of the catalytic core of the human Topo IIα bound to DNA and etoposide, providing insight into the regulation of Topo IIα activities and how opening of the DNA-gate is spatially connected to the ATPase domain.
Published: 2021

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