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214 results on '"Sophia Antipolis"'

1. Longevity strategies in response to light in the reef coral Stylophora pistillata

Author: Ottaviani, Alexandre, Eid, Rita, Zoccola, Didier, Pousse, Mélanie, Dubal, Jean-Marc, Barajas, Edwige, Jamet, Karine, Lebrigand, Kevin, Lapébie, Pascal, Baudoin, Christian, Giraud-Panis, M.J., Rouan, Alice, Beauchef, Gallic, Guéré, Christelle, Vié, Katell, Barbry, Pascal, Tambutté, Sylvie, Gilson, Eric, Allemand, Denis, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 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), Centre Scientifique de Monaco, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Giraud-Panis, Marie-Josèphe
Subjects: Marine biology, Cell biology, Light, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Coral Reefs, Longevity, fungi, lcsh:R, lcsh:Medicine, Forkhead Transcription Factors, Anthozoa, Senescence, Article, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, [SDV.BA.ZI] Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Circadian rhythms, lcsh:Q, Photosynthesis, lcsh:Science
Abstract: International audience; Aging is a multifactorial process that results in progressive loss of regenerative capacity and tissue function while simultaneously favoring the development of a large array of age-related diseases. Evidence suggests that the accumulation of senescent cells in tissue promotes both normal and pathological aging. Oxic stress is a key driver of cellular senescence. Because symbiotic long-lived reef corals experience daily hyperoxic and hypoxic transitions, we hypothesized that these long-lived animals have developed specific longevity strategies in response to light. We analyzed transcriptome variation in the reef coral Stylophora pistillata during the day–night cycle and revealed a signature of the FoxO longevity pathway. We confirmed this pathway by immunofluorescence using antibodies against coral FoxO to demonstrate its nuclear translocation. Through qPCR analysis of nycthemeral variations of candidate genes under different light regimens, we found that, among genes that were specifically up- or downregulated upon exposure to light, human orthologs of two “light-up” genes (HEY1 and LONF3) exhibited anti-senescence properties in primary human fibroblasts. Therefore, these genes are interesting candidates for counteracting skin aging. We propose a large screen for other light-up genes and an investigation of the biological response of reef corals to light (e.g., metabolic switching) to elucidate these processes and identify effective interventions for promoting healthy aging in humans.
Published: 2020

2. Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor

Author: Nuria Guerrero-Celis, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Marie-Pierre Cros, Chloe Goldsmith, Jesús Rafael Rodríguez-Aguilera, Szilvia Ecsedi, Mariana Domínguez-López, Rebeca Pérez-Cabeza de Vaca, Isabelle Chemin, Hector Hernandez-Vargas, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Institut de Biologie Valrose (IBV), 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), 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), Molecular Mechanisms and Biomarkers Group [Lyon], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institute for Social Security and Services for State Workers [Mexico, Mexique] (ISSSTE), Translational research and innovation department [Lyon], Centre Léon Bérard [Lyon], This work was supported by the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS, Reference No. ECTZ47287 and ECTZ50137), the Institut National du Cancer AAP PLBIO 2017 (project: T cell tolerance to microbiota and colorectal cancers), La Ligue Nationale Contre Le Cancer Comité d’Auvergne-Rhône-Alpes AAP 2018, Dirección General de Asuntos del Personal Académico/Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (DGAPA/PAPIIT-UNAM Grant number IN208915), Grant by Vela Advisor SA de CV to VCS Project, PhD Fellowship from Consejo Nacional de Ciencia y Tecnología to JRRA (CONACyT CVU 508509), Research Assistant Fellowship from Sistema Nacional de Investigadores to JRRA (SNI-CONACyT EXP. INV. 12666 EXP. AYTE. 7507), International Research Internship Support to JRRA from Programa de Apoyo a los Estudios de Posgrado del Programa de Maestría y Doctorado en Ciencias Bioquímicas (PAEP-UNAM No. Cta. 30479367-5), CONACyT (Beca Mixta CVU 508509), Stipend Supplement from IARC (Ref. STU. 2052), and Aide au logement from CAF (No Allocataire: 4384941 W) and ROAL660122., Bodescot, Myriam, Universidad Nacional Autónoma de México (UNAM), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Immunity, Virus and Inflammation [Lyon], and 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]-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Epigenomics, Cell, lcsh:Medicine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, Mixed Function Oxygenases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Proto-Oncogene Proteins, Gene expression, Cancer genomics, medicine, Humans, Progenitor cell, Promoter Regions, Genetic, lcsh:Science, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Gene, 030304 developmental biology, Progenitor, 5-Hydroxymethylcytosine, 0303 health sciences, DNA methylation, Genome, Multidisciplinary, Stem Cells, lcsh:R, Gene Expression Regulation, Developmental, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Differentiation, Promoter, Cell biology, DNA Demethylation, medicine.anatomical_structure, DNA demethylation, Hepatocyte Nuclear Factor 4, chemistry, 030220 oncology & carcinogenesis, 5-Methylcytosine, Hepatocytes, lcsh:Q
Abstract: A basic question linked to differential patterns of gene expression is how cells reach different fates despite using the same DNA template. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity, HNF4A, which precedes differentiation of liver adult progenitor cells in vitro. Here, we studied the genome-wide distribution of 5hmC at early in vitro differentiation of human hepatocyte-like cells. We found a global increase in 5hmC as well as a drop in 5-methylcytosine after one week of in vitro differentiation from bipotent progenitors, at a time when the liver transcript program is already established. 5hmC was overall higher at the bodies of overexpressed genes. Furthermore, by modifying the metabolic environment, an adenosine derivative prevents 5hmC enrichment and impairs the acquisition of hepatic identity markers. These results suggest that 5hmC could be a marker of cell identity, as well as a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.
Published: 2020

3. Generation of a conditional transgenic mouse model expressing human Phospholipase A2 Receptor 1

Author: Philippe Bertolino, Sara Jaber, Delphine Goehrig, Gérard Lambeau, Amélie Massemin, David Vindrieux, David Bernard, Joëlle Chabry, Franck Bihl, 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), This work was supported by ANR (ANR‐14‐CE12‐0003) to DB and by la Ligue contre le cancer, comité de la Savoie, to DB and DV, and the comité de l’Allier, to DV, by Fondation Maladies Rares (LAM-RD_20170304), ANR (MNaims ANR-17-CE17-0012-01) and the Fondation de la Recherche Médicale (DEQ20180339193) to GL. AM is supported by the Ligue Nationale contre le Cancer., ANR-14-CE12-0003,PROPLAGE,Rôle de la voie Progerin-PLA2R1 dans la sénescence cellulaire et le vieillissment(2014), ANR-17-CE17-0012,MNaims,Dissection moléculaire de la glomérulonéphrite extramembraneuse liée à PLA2R1: vers l'identification de nouveaux biomarqueurs cliniques(2017), Bodescot, Myriam, Appel à projets générique - Rôle de la voie Progerin-PLA2R1 dans la sénescence cellulaire et le vieillissment - - PROPLAGE2014 - ANR-14-CE12-0003 - Appel à projets générique - VALID, Dissection moléculaire de la glomérulonéphrite extramembraneuse liée à PLA2R1: vers l'identification de nouveaux biomarqueurs cliniques - - MNaims2017 - ANR-17-CE17-0012 - AAPG2017 - VALID, 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Genetically modified mouse, Genotyping Techniques, Science, Gene Expression, Cre recombinase, Mice, Transgenic, Inflammation, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Biology, Article, Mice, 03 medical and health sciences, Medical research, 0302 clinical medicine, Membranous nephropathy, medicine, Animals, Humans, Biological models, Multidisciplinary, Mechanism (biology), Receptors, Phospholipase A2, Lectin, Cancer, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], medicine.disease, Pathophysiology, Cell biology, Disease Models, Animal, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Organ Specificity, 030220 oncology & carcinogenesis, biology.protein, Medicine, medicine.symptom
Abstract: The Phospholipase A2 Receptor 1 (PLA2R1) was first identified for its ability to bind some secreted PLA2s (sPLA2s). It belongs to the C-type lectin superfamily and it binds different types of proteins. It is likely a multifunctional protein that plays a role i) in inflammation and inflammatory diseases, ii) in cellular senescence, a mechanism participating in aging and age-related diseases including cancer, and iii) in membranous nephropathy (MN), a rare autoimmune kidney disease where PLA2R1 is the major autoantigen. To help study the role of PLA2R1 in these pathophysiological conditions, we have generated a versatile NeoR-hPLA2R1 conditional transgenic mice which will allow the specific expression of human PLA2R1 (hPLA2R1) in relevant organs and cells following Cre recombinase-driven excision of the NeoR-stop cassette flanked by LoxP sites. Proof-of-concept breeding of NeoR-hPLA2R1 mice with the ubiquitous adenoviral EIIa promoter-driven Cre mouse line resulted in the expected excision of the NeoR-stop cassette and the expression of hPLA2R1 in all tested tissues. These Tg-hPLA2R1 animals breed normally, with no reproduction or apparent growth defect. These models, especially the NeoR-hPLA2R1 conditional transgenic mouse line, will facilitate the future investigation of PLA2R1 functions in relevant pathophysiological contexts, including inflammatory diseases, age-related diseases and MN.
Published: 2020

4. Depicting the genetic architecture of pediatric cancers through an integrative gene network approach

Author: Savary, Clara, Kim, Artem, Lespagnol, Alexandra, Gandemer, Virginie, Pellier, Isabelle, Andrieu, Charlotte, Pagès, Gilles, Galibert, Marie-Dominique, Blum, Yuna, de Tayrac, Marie, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 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), Centre Scientifique de Monaco (CSM), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), PRT-K16-155 2016, Institut National Du Cancer (French National Cancer Institute), PRT-K16-155 2016, Direction Générale de landapos, offre de Soins (DGOS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Jonchère, Laurent
Subjects: Male, Gene Expression, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Paediatric cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Databases, Genetic, Protein Interaction Mapping, Cancer genomics, Biomarkers, Tumor, Humans, Computer Simulation, Gene Regulatory Networks, Genetic Predisposition to Disease, Protein Interaction Maps, Child, lcsh:Science, Models, Statistical, Gene Expression Profiling, Computational science, lcsh:R, Computational Biology, Genomics, Gene Expression Regulation, Neoplastic, Systems Integration, Gene Expression Regulation, Child, Preschool, Female, lcsh:Q, Transcriptome
Abstract: International audience; The genetic etiology of childhood cancers still remains largely unknown. It is therefore essential to develop novel strategies to unravel the spectrum of pediatric cancer genes. Statistical network modeling techniques have emerged as powerful methodologies for enabling the inference of gene-disease relationship and have been performed on adult but not pediatric cancers. We performed a deep multi-layer understanding of pan-cancer transcriptome data selected from the Treehouse Childhood Cancer Initiative through a co-expression network analysis. We identified six modules strongly associated with pediatric tumor histotypes that were functionally linked to developmental processes. Topological analyses highlighted that pediatric cancer predisposition genes and potential therapeutic targets were central regulators of cancer-histotype specific modules. A module was related to multiple pediatric malignancies with functions involved in DNA repair and cell cycle regulation. This canonical oncogenic module gathered most of the childhood cancer predisposition genes and clinically actionable genes. In pediatric acute leukemias, the driver genes were co-expressed in a module related to epigenetic and post-transcriptional processes, suggesting a critical role of these pathways in the progression of hematologic malignancies. This integrative pan-cancer study provides a thorough characterization of pediatric tumor-associated modules and paves the way for investigating novel candidate genes involved in childhood tumorigenesis.
Published: 2020

5. Chimeric virus-like particles (VLPs) designed from shrimp nodavirus (MrNV) capsid protein specifically target EGFR-positive human colorectal cancer cells

Author: Krittalak Chakrabandhu, Orawan Thongsum, Charoonroj Chotwiwatthanakun, Sébastien Huault, Pitchanee Jariyapong, Chidchanok Chawiwithaya, Wattana Weerachatyanukul, Anne-Odile Hueber, Khwanthana Grataitong, Mahidol University [Bangkok], Navamindradhiraj University [Bangkok], Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Walailak University, 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 HUEBER, Anne-Odile
Subjects: viruses, Drug Compounding, Recombinant Fusion Proteins, [SDV]Life Sciences [q-bio], Science, DNA, Recombinant, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sf9, 02 engineering and technology, Adenocarcinoma, Biology, Article, Virus, law.invention, 03 medical and health sciences, Drug Delivery Systems, Plasmid, [SDV.CAN] Life Sciences [q-bio]/Cancer, Nanoscience and technology, law, Cell Line, Tumor, medicine, Humans, Gene silencing, Nodaviridae, Molecular Targeted Therapy, Cancer, 030304 developmental biology, 0303 health sciences, Multidisciplinary, 021001 nanoscience & nanotechnology, medicine.disease, Virology, Neoplasm Proteins, ErbB Receptors, [SDV] Life Sciences [q-bio], Capsid, Drug Design, Cancer cell, Recombinant DNA, Medicine, Capsid Proteins, Colorectal Neoplasms, Peptides, 0210 nano-technology
Abstract: Recombinant MrNV capsid protein has been shown to effectively deliver plasmid DNA and dsRNA into Sf9 insect cells and shrimp tissues. To extend its application to cancer cell-targeting drug delivery, we created three different types of chimeric MrNV virus-like particles (VLPs) (R-MrNV, I-MrNV, and E-MrNV) that have specificity toward the epidermal growth factor receptor (EGFR), a cancer cell biomarker, by incorporating the EGFR-specific GE11 peptide at 3 different locations within the host cell recognition site of the capsid. All three chimeric MrNV-VLPs preserved the ability to form a mulberry-like VLP structure and to encapsulate EGFP DNA plasmid with an efficiency comparable to that previously reported for normal MrNV (N-MrNV). Compared to N-MrNV, the chimeric R-MrNV and E-MrNV carrying the exposed GE-11 peptide showed a significantly enhanced binding and internalization abilities that were specific towards EGFR expression in colorectal cancer cells (SW480). Specific targeting of chimeric MrNV to EGFR was proven by both EGFR silencing with siRNA vector and a competition with excess GE-11 peptide as well as the use of EGFR-negative colorectal cells (SW620) and breast cancer cells (MCF7). We demonstrated here that both chimeric R-MrNV and E-MrNV could be used to encapsulate cargo such as exogenous DNA and deliver it specifically to EGFR-positive cells. Our study presents the potential use of surface-modified VLPs of shrimp virus origin as nanocontainers for targeted cancer drug delivery.
Published: 2021

6. Notch-mediated inhibition of neurogenesis is required for zebrafish spinal cord morphogenesis

Author: Priyanka Sharma, Maximilian Fürthauer, Li Xiang, Vishnu Muraleedharan Saraswathy, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), RUIZ, Caroline, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Nervous system, Neural Tube, Neurogenesis, Notch signaling pathway, Neuroepithelial Tissue, lcsh:Medicine, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Morphogenesis, Animals, lcsh:Science, Zebrafish, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Multidisciplinary, Receptors, Notch, lcsh:R, Neural tube, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Development of the nervous system, Cell Differentiation, Zebrafish Proteins, biology.organism_classification, Neuroepithelial cell, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, lcsh:Q, Neuroscience, Neural development, 030217 neurology & neurosurgery, Cell signalling
Abstract: The morphogenesis of the nervous system requires coordinating the specification and differentiation of neural precursor cells, the establishment of neuroepithelial tissue architecture and the execution of specific cellular movements. How these aspects of neural development are linked is incompletely understood. Here we inactivate a major regulator of embryonic neurogenesis - the Delta/Notch pathway - and analyze the effect on zebrafish central nervous system morphogenesis. While some parts of the nervous system can establish neuroepithelial tissue architecture independently of Notch, Notch signaling is essential for spinal cord morphogenesis. In this tissue, Notch signaling is required to repress neuronal differentiation and allow thereby the emergence of neuroepithelial apico-basal polarity. Notch-mediated suppression of neurogenesis is also essential for the execution of specific morphogenetic movements of zebrafish spinal cord precursor cells. In the wild-type neural tube, cells divide at the organ midline to contribute one daughter cell to each organ half. Notch signaling deficient animals fail to display this behavior and therefore form a misproportioned spinal cord. Taken together, our findings show that Notch-mediated suppression of neurogenesis is required to allow the execution of morphogenetic programs that shape the zebrafish spinal cord.
Published: 2019

7. Diffraction-less propagation beyond the sub-wavelength regime: a new type of nanophotonic waveguide

Author: Elena Durán-Valdeiglesias, Dorian Oser, Delphine Marris-Morini, Diego Perez-Galacho, Daniel Benedikovic, Xavier Le Roux, Carlos Alonso-Ramos, Sébastien Tanzilli, Jianhao Zhang, Vladyslav Vakarin, Eric Cassan, Florent Mazeas, Laurent Vivien, Pavel Cheben, Laurent Labonté, Centre de Nanosciences et de Nanotechnologies [Orsay] (C2N), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Nice (UMR 7010 CNRS-UNS), Institut Non Linéaire de Nice (INLN)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), PHOTONIQUE (XLIM-PHOTONIQUE), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de la Matière Condensée (LPMC), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut d'électronique fondamentale (IEF), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), National Research Council of Canada (NRC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut Non Linéaire de Nice (INLN), and Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Diffraction, Nanophotonics, Physics::Optics, lcsh:Medicine, Degrees of freedom (mechanics), Grating, 7. Clean energy, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, lcsh:Science, Physics, Multidisciplinary, Silicon photonics, business.industry, lcsh:R, Metamaterial, 030104 developmental biology, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Optoelectronics, lcsh:Q, Photonics, business, Waveguide, 030217 neurology & neurosurgery
Abstract: International audience; Sub-wavelength grating (SWG) metamaterials have garnered a great interest for their singular capability to shape the propagation of light. However, practical SWG implementations are limited by fabrication constraints, such as minimum feature size. Here, we present a new nanophotonic waveguide grating concept that exploits phase-matching engineering to suppress diffraction effects for a period three times larger than those with SWG approaches. This long-period grating not only facilitates fabrication, but also enables a new diffraction-less regime with additional degrees of freedom to control light propagation. More specifically, the proposed phase-matching engineering enables selective diffraction suppression, providing new tools to shape propagation in the grating. We harness this flexible diffraction control to yield single-mode propagation in, otherwise, highly multimode waveguides, and to implement Bragg filters that combine highly-diffractive and diffraction-less regions to dramatically increase light rejection. Capitalizing on this new concept, we experimentally demonstrate a Si membrane Bragg filter with record rejection value exceeding 60 dB. These results demonstrate the potential of the proposed long-period grating for the engineering of diffraction in nanophotonic waveguides and pave the way for the development of a new generation of high-performance Si photonics devices. Silicon photonics is widely recognized as an enabling technology for next generation optical interconnects, holding the promise of providing ultra-compact and low power consumption opto-electronic transceivers, fabricated at large volumes leveraging existing CMOS facilities 1. Driven by the impressive technological development over the recent years, silicon photonics is expanding its frontiers towards new applications beyond datacom 2. These include, among others, chemical and biological sensing 3 , radio-over-fiber 4 , spectroscopy 5 , and quantum cryptography 6. In this very diverse ecosystem, combining demanding optical interconnects with disruptive new applications , sub-wavelength grating (SWG) engineering has gained momentum due to its unmatched flexibility in controlling the propagation of light in nanophotonic devices 7,8. SWG metamaterial waveguides rely on periodic silicon patterning, with a structural period shorter than half the wavelength, to synthesize refractive index and chromatic dispersion that can, in principle, be engineered at will 9,10. Unlike photonic crystals that rely on resonant light confinement 11 , SWG waveguides operate well below the bandgap, guiding light by (synthetic) refractive index difference. This way, they provide flexible control over modal confinement, birefringence and dispersion, non-achievable in conventional waveguide arrangements, alongside with low propagation loss and remarkably wide spectral bandwidth 9,10,12,13. These key advantages allowed the demonstration of several SWG-based devices
Published: 2019

8. Cardiac dyspnea risk zones in the South of France identified by geo-pollution trends study

Author: Fanny Simões, Charles Bouveyron, Damien Piga, Damien Borel, Stéphane Descombes, Véronique Paquis-Flucklinger, Jaques Levraut, Pierre Gibelin, Silvia Bottini, Université Côte d'Azur (UCA), Modèles et algorithmes pour l’intelligence artificielle (MAASAI), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Laboratoire Jean Alexandre Dieudonné (LJAD), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Scalable and Pervasive softwARe and Knowledge Systems (Laboratoire I3S - SPARKS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), AtmoSud, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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 Hôpital Pasteur [Nice] (CHU)
Subjects: Adult, Male, Quality of life, Time Factors, Disease prevention, Science, Cardiology, Nitric Oxide, Risk Assessment, Article, Young Adult, Ozone, Risk Factors, Weight management, Humans, Aged, Aged, 80 and over, Heart Failure, Air Pollutants, Inhalation Exposure, Public health, Incidence, Health care, Middle Aged, Health policy, [STAT]Statistics [stat], Dyspnea, [SDE]Environmental Sciences, Medicine, Female, Particulate Matter, France, Environmental Pollution, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Environmental Monitoring
Abstract: International audience; Background. The incidence of cardiac dyspnea (CD) and the distribution of pollution in the south of France suggests that environmental pollution may have a role in disease triggering. CD is a hallmark symptom of heart failure leading to reduced ability to function and engage in activities of daily living. Methods. To show the impact of short-term pollution exposure on the increment of CD emergency room visits, we collected pollutants and climate measurements on a daily basis and 43,400 events of CD in the Région Sud from 2013 to 2018. We used a distributed lag non-linear model (DLNM) to assess the association between air pollution and CD events. We divided the region in 357 zones to reconciliate environmental and emergency room visits data. We applied the DLNM on the entire region, on zones grouped by pollution trends and on singular zones. Results. Each pollutant has a significant effect on triggering CD. Depending on the pollutant, we identified four shapes of exposure curves to describe the impact of pollution on CD events: early and late effect for NO 2 ; U-shape and rainbow-shape (or inverted U) for O 3 ; all the four shapes for PM10. In the biggest cities, O 3 has the most significant association along with the PM10. In the west side, a delayed effect triggered by PM10 was found. Zones along the main highway are mostly affected by NO 2 pollution with an increase of the association for a period up to 9 days after the pollution peak. Conclusions. Our results can be used by local authorities to set up specific prevention policies, public alerts that adapt to the different zones and support public health predictionmaking. We developed a user-friendly web application called HEART (Health, Environment in PACA Region Tool) to collect our results. HEART will allow citizens, researchers and local authorities to monitor the impact of pollution trends on local public health.
Published: 2021

9. Modelling transport of inhibiting and activating signals and their combined effects on floral induction: application to apple tree

Author: Belhassine, Fares, Fumey, Damien, Chopard, Jérôme, Pradal, Christophe, Martinez, Sébastien, Costes, Evelyne, Pallas, Benoît, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, 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), ITK [Clapiers], Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Scientific Data Management (ZENITH), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Architecture et Fonctionnement des Espèces Fruitières [AGAP] (AFEF), 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)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, INRA (BAP department), ITK company, ANR-14-CE35-0001,AlternApp,Genetic mechanisms underlying alternate cropping in apple (Malus x domestica)(2014), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Inria Sophia Antipolis - Méditerranée (CRISAM), and 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)
Subjects: F60 - Physiologie et biochimie végétale, Meristem, lcsh:Medicine, Models, Biological, Article, Flowering, Floraison, Computational models, lcsh:Science, Shoot apical meristem, U10 - Informatique, mathématiques et statistiques, lcsh:R, food and beverages, Biological Transport, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, Plant signalling, Malus, lcsh:Q, Modèle végétal, signal, Modèle mathématique, Signal Transduction
Abstract: International audience; Floral induction (FI) in shoot apical meristems (SAM) is assumed to be triggered by antagonistic endogenous signals. In fruit trees, FI occurs in some SAM only and is determined by activating and inhibiting signals originating from leaves and fruit, respectively. We developed a model (SigFlow) to quantify on 3D structures the combined impact of such signals and distances at which they act on SAM. Signal transport was simulated considering a signal ‘attenuation’ parameter, whereas SAM fate was determined by probability functions depending on signal quantities. Model behaviour was assessed on simple structures before being calibrated and validated on a unique experimental dataset of 3D digitized apple trees with contrasted crop loads and subjected to leaf and fruit removal at different scales of tree organization. Model parameter estimations and comparisons of two signal combination functions led us to formulate new assumptions on the mechanisms involved: (i) the activating signal could be transported at shorter distances than the inhibiting one (roughly 50 cm vs 1 m) (ii) both signals jointly act to determine FI with SAM being more sensitive to inhibiting signal than activating one. Finally, the genericity of the model is promising to further understand the physiological and architectural determinisms of FI in plants.
Published: 2020

10. New Structural insights into Kir channel gating from molecular simulations, HDX-MS and functional studies

Author: Iman Oubella, David Perahia, Catherine Vénien-Bryan, Yasmina Mhoumadi, Aline de Araujo, Saïd Bendahhou, Charline Fagnen, Rita De Zorzi, Ludovic Bannwarth, Eric Forest, 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), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Université Grenoble Alpes (UGA), University of Trieste, Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Fagnen, C., Bannwarth, L., Oubella, I., Forest, E., De Zorzi, R., de Araujo, A., Mhoumadi, Y., Bendahhou, S., Perahia, D., Venien-Bryan, C., Università degli studi di Trieste = University of Trieste, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: 0301 basic medicine, Guanine Nucleotide Binding Protein, Protein Conformation, In silico, Lipid Bilayers, lcsh:Medicine, Inwardly Rectifying Potassium Channels, Kir2.1 Channel, Hydrogen Deuterium Exchange-Mass Spectrometry, Gating, Molecular Dynamics Simulation, Article, 03 medical and health sciences, Molecular dynamics, 0302 clinical medicine, Protein structure, Computer Simulation, Potassium Channels, Inwardly Rectifying, lcsh:Science, Physics, Inwardly Rectifying Potassium Channel, Multidisciplinary, Mass spectrometry, Inward-rectifier potassium ion channel, lcsh:R, [PHYS.PHYS.PHYS-ATM-PH]Physics [physics]/Physics [physics]/Atomic and Molecular Clusters [physics.atm-clus], Potassium channel, Electrophysiology, Transmembrane domain, 030104 developmental biology, lcsh:Q, Molecular modelling, Ion Channel Gating, Neuroscience, 030217 neurology & neurosurgery
Abstract: Inward rectifier potassium (Kir) channels play diverse and important roles in shaping action potentials in biological membranes. An increasing number of diseases are now known to be directly associated with abnormal Kir function. However, the gating of Kir still remains unknown. To increase our understanding of its gating mechanism, a dynamical view of the entire channel is essential. Here the gating activation was studied using a recent developped in silico method, MDeNM, which combines normal mode analysis and molecular dynamics simulations that showed for the very first time the importance of interrelated collective and localized conformational movements. In particular, we highlighted the role played by concerted movements of the different regions throughout the entire protein, such as the cytoplasmic and transmembrane domains and the slide helices. In addition, the HDX-MS analysis achieved in these studies provided a comprehensive and detailed view of the dynamics associated with open/closed transition of the Kir channel in coherence with the theoretical results. MDeNM gives access to the probability of the different opening states that are in agreement with our electrophysiological experiments. The investigations presented in this article are important to remedy dysfunctional channels and are of interest for designing new pharmacological compounds.
Published: 2020

11. Gravitational models explain shifts on human visual attention

Author: Alessandra Rufa, Marco Gori, Dario Zanca, Stefano Melacci, Università degli Studi di Siena = University of Siena (UNISI), Dipartimento di Ingegneria dell'informazione e scienze matematiche [Siena] (DIISM), Modèles et algorithmes pour l’intelligence artificielle (MAASAI), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Laboratoire Jean Alexandre Dieudonné (JAD), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Scalable and Pervasive softwARe and Knowledge Systems (Laboratoire I3S - SPARKS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Laboratoire Jean Alexandre Dieudonné (LJAD), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Scalable and Pervasive softwARe and Knowledge Systems (Laboratoire I3S - SPARKS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: FOS: Computer and information sciences, Elementary cognitive task, Computer Science - Machine Learning, Eye Movements, Computer science, Computer Science - Artificial Intelligence, Computer Vision and Pattern Recognition (cs.CV), Models, Neurological, Computer Science - Computer Vision and Pattern Recognition, lcsh:Medicine, Sensory system, 02 engineering and technology, Image (mathematics), Machine Learning (cs.LG), 03 medical and health sciences, 0302 clinical medicine, Salience (neuroscience), Attractor, 0202 electrical engineering, electronic engineering, information engineering, medicine, Visual attention, Humans, Saliency map, Attention, lcsh:Science, Computational model, Multidisciplinary, Pixel, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, Process (computing), Pattern recognition, Human brain, medicine.anatomical_structure, Artificial Intelligence (cs.AI), Feature (computer vision), Visual Perception, 020201 artificial intelligence & image processing, lcsh:Q, Artificial intelligence, business, 030217 neurology & neurosurgery, Photic Stimulation
Abstract: Visual attention refers to the human brain’s ability to select relevant sensory information for preferential processing, improving performance in visual and cognitive tasks. It proceeds in two phases. One in which visual feature maps are acquired and processed in parallel. Another where the information from these maps is merged in order to select a single location to be attended for further and more complex computations and reasoning. Its computational description is challenging, especially if the temporal dynamics of the process are taken into account. Numerous methods to estimate saliency have been proposed in the last 3 decades. They achieve almost perfect performance in estimating saliency at the pixel level, but the way they generate shifts in visual attention fully depends on winner-take-all (WTA) circuitry. WTA is implemented by the biological hardware in order to select a location with maximum saliency, towards which to direct overt attention. In this paper we propose a gravitational model to describe the attentional shifts. Every single feature acts as an attractor and the shifts are the result of the joint effects of the attractors. In the current framework, the assumption of a single, centralized saliency map is no longer necessary, though still plausible. Quantitative results on two large image datasets show that this model predicts shifts more accurately than winner-take-all.
Published: 2020

12. Hyperprogression under Immune Checkpoint Inhibitor: a potential role for germinal immunogenetics

Author: Frederic Peyrade, Gérard Milano, Patrick Brest, Jocelyn Gal, Sadal Refae, Joël Guigay, Nathalie Ebran, Delphine Borchiellini, Damien Giacchero, Esma Saada-Bouzid, Bodescot, Myriam, Oncopharmacology Unit [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Epidemiology and Biostatistics Department [Nice], Pathologies liées à l’âge [Nice] (FHU OncoAge), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-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)-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), Medical Oncology Department [Nice], The authors acknowledge support from Centre Antoine Lacassagne, Oncopharmacology unit team, University Côte d’Azur, France., COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), and 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)-Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Male, Candidate gene, medicine.medical_treatment, Programmed Cell Death 1 Receptor, lcsh:Medicine, Immunogenetics, B7-H1 Antigen, 0302 clinical medicine, Neoplasms, lcsh:Science, Immune Checkpoint Inhibitors, Aged, 80 and over, 0303 health sciences, Univariate analysis, Multidisciplinary, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Toxicity, Disease Progression, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Adult, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Predictive markers, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer epigenetics, medicine, Humans, Author Correction, Aged, Cell Proliferation, 030304 developmental biology, business.industry, lcsh:R, Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Immunotherapy, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Cancer research, lcsh:Q, business
Abstract: Hyperprogressive disease (HPD), an unexpected acceleration of tumor growth kinetics, is described in cancer patients treated with anti-PD-1/anti-PD-L1 agents. Here, our aim was to take into consideration the host and explore whether single nucleotide polymorphisms (SNPs) in key genes involved in immune response might predispose to HPD. DNA was extracted from blood-samples from 98 patients treated under CPI monotherapy. Four candidate genes (PD-1, PD-L1, IDO1 and VEGFR2) and 15 potential SNPs were selected. The TGKR (ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR≥2. TGKR calculation was feasible for 80 patients (82%). HPD was observed for 11 patients (14%) and was associated with shorter overall survival (P = 0.003). In univariate analysis, HPD was significantly associated with age ≥70 y (P = 0.025), immune-related toxicity (P = 0.016), VEGFR2 rs1870377 A/T or A/A (P = 0.005), PD-L1 rs2282055 G/T or G/G (P = 0.024) and PD-L1 rs2227981 G/A or A/A (P = 0.024). Multivariate analysis confirmed the correlation between HPD and age ≥70 y (P = 0.006), VEGFR2 rs1870377 A/T or A/A (P = 0.007) and PD-L1 rs2282055 G/T or G/G (P = 0.018). Immunogenetics could become integral predictive factors for CPI-based immunotherapy.
Published: 2020

13. A204E mutation in Nav1.4 DIS3 exerts gain- and loss-of-function effects that lead to periodic paralysis combining hyper- with hypo-kalaemic signs

Author: Kokunai, Yosuke, Dalle, Carine, Vicart, Savine, Sternberg, Damien, Pouliot, Valérie, Bendahhou, Saïd, Fournier, Emmanuel, Chahine, Mohamed, Fontaine, Bertrand, Nicole, Sophie, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval), Laboratoire de PhysioMédecine Moléculaire (LP2M), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Gestionnaire, Hal Sorbonne Université, 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Faculté de médecine de l'Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, lcsh:R, lcsh:Medicine, lcsh:Q, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, lcsh:Science, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Periodic paralyses (PP) are characterized by episodic muscle weakness and are classified into the distinct hyperkalaemic (hyperPP) and hypokalaemic (hypoPP) forms. The dominantly-inherited form of hyperPP is caused by overactivity of Nav1.4 — the skeletal muscle voltage-gated sodium channel. Familial hypoPP results from a leaking gating pore current induced by dominant mutations in Nav1.4 or Cav1.1, the skeletal muscle voltage-gated calcium channel. Here, we report an individual with clinical signs of hyperPP and hypokalaemic episodes of muscle paralysis who was heterozygous for the novel p.Ala204Glu (A204E) substitution located in one region of Nav1.4 poor in disease-related variations. A204E induced a significant decrease of sodium current density, increased the window current, enhanced fast and slow inactivation of Nav1.4, and did not cause gating pore current in functional analyses. Interestingly, the negative impact of A204E on Nav1.4 activation was strengthened in low concentration of extracellular K+. Our data prove the existence of a phenotype combining signs of hyperPP and hypoPP due to dominant Nav1.4 mutations. The hyperPP component would result from gain-of-function effects on Nav1.4 and the hypokalemic episodes of paralysis from loss-of-function effects strengthened by low K+. Our data argue for a non-negligible role of Nav1.4 loss-of-function in familial hypoPP.
Published: 2018

14. Identification and characterization of two zebrafish Twik related potassium channels, Kcnk2a and Kcnk2b

Author: Nasr, Nathalie, Faucherre, Adèle, Borsotto, Marc, Heurteaux, Catherine, Mazella, Jean, Jopling, Chris, Moha ou Maati, Hamid, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Mazella, Jean, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: Riluzole, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:Medicine, Zebrafish Proteins, Article, Membrane Potentials, HEK293 Cells, Neuroprotective Agents, Potassium Channels, Tandem Pore Domain, Fluoxetine, Animals, Antidepressive Agents, Second-Generation, Humans, Protein Isoforms, lcsh:Q, Peptides, lcsh:Science, Ion Channel Gating, Cells, Cultured, Zebrafish, ComputingMilieux_MISCELLANEOUS
Abstract: KCNK2 is a 2 pore domain potassium channel involved in maintaining cellular membrane resting potentials. Although KCNK2 is regarded as a mechanosensitive ion channel, it can also be gated chemically. Previous research indicates that KCNK2 expression is particularly enriched in neuronal and cardiac tissues. In this respect, KCNK2 plays an important role in neuroprotection and has also been linked to cardiac arrhythmias. KCNK2 has subsequently become an attractive pharmacologic target for developing preventative/curative strategies for neuro/cardio pathophysiological conditions. Zebrafish represent an important in vivo model for rapidly analysing pharmacological compounds. We therefore sought to identify and characterise zebrafish kcnk2 to allow this model system to be incorporated into therapeutic research. Our data indicates that zebrafish possess two kcnk2 orthologs, kcnk2a and kcnk2b. Electrophysiological analysis of both zebrafish Kcnk2 orthologs shows that, like their human counterparts, they are activated by different physiological stimuli such as mechanical stretch, polyunsaturated fatty acids and intracellular acidification. Furthermore, both zebrafish Kcnk2 channels are inhibited by the human KCNK2 inhibitory peptide spadin. Taken together, our results demonstrate that both Kcnk2a and Kcnk2b share similar biophysiological and pharmacological properties to human KCNK2 and indicate that the zebrafish will be a useful model for developing KCNK2 targeting strategies.
Published: 2018

15. Carboxythiazole is a key microbial nutrient currency and critical component of thiamin biosynthesis

Author: Phillippe Schatt, Thomas D. Niehaus, Elden E. Rowland, Andrew D. Hanson, Mohamed Mehiri, Lasse Riemann, Ryan W. Paerl, Erin M. Bertrand, François-Yves Bouget, Department of Marine, Earth, and Atmospheric Sciences [NCSU] (MEAS), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Biology [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Department of Biology (Dalhousie University), Dalhousie University [Halifax], Laboratoire d'Océanographie Microbienne (LOMIC), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Nice (ICN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Horticultural Sciences Department, University of Florida [Gainesville], ANR: 15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), ANR-14-CE02-0018,Photo-Phyto,Effets du réchauffement climatique sur le déclenchement des blooms phytoplanctoniques marins : photoperiodisme, composition et adaptation(2014), European Project: 654008,H2020,H2020-INFRADEV-1-2014-1,EMBRIC(2015), University of North Carolina System (UNC), University of Copenhagen = Københavns Universitet (KU), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Florida [Gainesville] (UF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)
Subjects: 0106 biological sciences, 0301 basic medicine, Water microbiology, Microorganism, Arabidopsis, lcsh:Medicine, Chemical ecology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Biology, medicine.disease_cause, 01 natural sciences, Article, Cell Line, Microbial ecology, 03 medical and health sciences, Thiamine biosynthesis, chemistry.chemical_compound, Mice, Nutrient, Biosynthesis, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Escherichia coli, Arabidopsis thaliana, Animals, Thiamine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:Science, Primary productivity, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Multidisciplinary, Arabidopsis Proteins, lcsh:R, Nutrients, biology.organism_classification, Thiazoles, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, chemistry, Phytoplankton, lcsh:Q, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, 010606 plant biology & botany
Abstract: Almost all cells require thiamin, vitamin B1 (B1), which is synthesized via the coupling of thiazole and pyrimidine precursors. Here we demonstrate that 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole-2-carboxylic acid (cHET) is a useful in vivo B1 precursor for representatives of ubiquitous marine picoeukaryotic phytoplankton and Escherichia coli – drawing attention to cHET as a valuable exogenous micronutrient for microorganisms with ecological, industrial, and biomedical value. Comparative utilization experiments with the terrestrial plant Arabidopsis thaliana revealed that it can also use exogenous cHET, but notably, picoeukaryotic marine phytoplankton and E. coli were adapted to grow on low (picomolar) concentrations of exogenous cHET. Our results call for the modification of the conventional B1 biosynthesis model to incorporate cHET as a key precursor for B1 biosynthesis in two domains of life, and for consideration of cHET as a microbial micronutrient currency modulating marine primary productivity and community interactions in human gut-hosted microbiomes.
Published: 2018

16. Substitutions of the S4DIV R2 residue (R1451) in NaV1.4 lead to complex forms of paramyotonia congenita and periodic paralyses

Author: Saïd Bendahhou, Pascal Gosselin-Badaroudine, Serena Giuliano, Savine Vicart, Mohamed Chahine, Hugo Poulin, Sophie Nicole, Damien Sternberg, Karima Habbout, Bertrand Fontaine, Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Myotonic Disorder, Mutation, Missense, lcsh:Medicine, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Missense mutation, Humans, NAV1.4 Voltage-Gated Sodium Channel, lcsh:Science, Mutation, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, lcsh:R, Skeletal muscle, Periodic paralysis, medicine.disease, Myotonia, Phenotype, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, Paramyotonia congenita, Biophysics, lcsh:Q, Ion Channel Gating, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Myotonic Disorders
Abstract: Mutations in NaV1.4, the skeletal muscle voltage-gated Na+ channel, underlie several skeletal muscle channelopathies. We report here the functional characterization of two substitutions targeting the R1451 residue and resulting in 3 distinct clinical phenotypes. The R1451L is a novel pathogenic substitution found in two unrelated individuals. The first individual was diagnosed with non-dystrophic myotonia, whereas the second suffered from an unusual phenotype combining hyperkalemic and hypokalemic episodes of periodic paralysis (PP). The R1451C substitution was found in one individual with a single attack of hypoPP induced by glucocorticoids. To elucidate the biophysical mechanism underlying the phenotypes, we used the patch-clamp technique to study tsA201 cells expressing WT or R1451C/L channels. Our results showed that both substitutions shifted the inactivation to hyperpolarized potentials, slowed the kinetics of inactivation, slowed the recovery from slow inactivation and reduced the current density. Cooling further enhanced these abnormalities. Homology modeling revealed a disruption of hydrogen bonds in the voltage sensor domain caused by R1451C/L. We concluded that the altered biophysical properties of R1451C/L well account for the PMC-hyperPP cluster and that additional factors likely play a critical role in the inter-individual differences of clinical expression resulting from R1451C/L.
Published: 2018

17. Counterbalancing anti-adhesive effects of Tenascin-C through fibronectin expression in endothelial cells

Author: Radwanska, Agata, Grall, Dominique, Schaub, Sébastien, Beghelli-de La, Stéphanie, Divonne, Forest, Ciais, Delphine, Rekima, Samah, Rupp, Tristan, Sudaka, Anne, Orend, Gertraud, van Obberghen-Schilling, Ellen, Divonne, Stéphanie Beghelli-de La Forest, Obberghen-Schilling, Ellen Van, Institut de Biologie Valrose (IBV), 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), Institut de signalisation, biologie du développement et cancer (ISBDC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Angiogenèse hormono-régulée et angiogenèse tumorale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Van Obberghen-Schilling, Ellen, Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Motility, Neovascularization, Physiologic, lcsh:Medicine, Matrix (biology), Models, Biological, Article, Cell-Matrix Junctions, Neovascularization, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Cell Movement, Neoplasms, medicine, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Humans, Cell adhesion, lcsh:Science, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Neovascularization, Pathologic, Chemistry, Tenascin C, lcsh:R, Tenascin, musculoskeletal system, Cell biology, Capillaries, Fibronectins, Fibronectin, 030104 developmental biology, 030220 oncology & carcinogenesis, Immunology, biology.protein, lcsh:Q, Signal transduction, medicine.symptom, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: International audience; Cellular fibronectin (FN) and tenascin-C (TNC) are prominent development-and disease-associated matrix components with pro-and anti-adhesive activity, respectively. Whereas both are present in the tumour vasculature, their functional interplay on vascular endothelial cells remains unclear. We have previously shown that basally-oriented deposition of a FN matrix restricts motility and promotes junctional stability in cultured endothelial cells and that this effect is tightly coupled to expression of FN. Here we report that TNC induces FN expression in endothelial cells. This effect counteracts the potent anti-adhesive activity of TNC and leads to the assembly of a dense highly-branched subendothelial matrix that enhances tubulogenic activity. These findings suggest that pro-angiogenic remodelling of the perivascular matrix may involve TNC-induced upregulation of FN in endothelial cells. Angiogenesis, the sprouting of new vasculature from a pre-existing vascular network, is an essential process during development, maintenance of tissues and metastatic spread of cancer. This multi-step process is tightly regulated and spatiotemporally controlled by various soluble cytokines, membrane-bound proteins, cell-matrix and cell-cell interactions and hemodynamic forces. In recent years it has become clear that dynamic remodelling of the extracellular matrix (ECM) is essential for all stages of angiogenesis. Through adhesive interactions with integrins expressed on the endothelial cell surface, the ECM orchestrates complex signalling cascades within the cells and affects many fundamental aspects of their biology, including proliferation, migration, cytoskeletal organization, cell shape, survival, and ultimately blood vessel stabilization (reviewed in 1). Tenascin-C (TNC) and alternatively spliced forms of fibronectin (FN) are principle ECM components of the angiogenic vasculature of tumours, yet barely detected in quiescent adult vessels (reviewed in 2). Genetic studies in mice and fish have pointed to a fundamental role for FN and its primary receptor α5β1 integrin in early blood vessel development and vascular physio-pathology (reviewed in 3,4). FN-null mice die at embryonic day 9.5 with severe cardiovascular defects 5 and α5 null mice display the most severe vascular defects of all the null phenotypes of α-encoding inte-grin genes 6. Although TNC knockout mice do not display an embryonic lethal phenotype 7,8 , TNC expression is highly associated with angiogenesis in a wide range of disease states, including cancer 9–11. Adhesive and counter-adhesive effects are attributed respectively to FN and TNC. One mechanism by which TNC modulates cell adhesion-dependent processes involves its direct interaction with FN, which leads to interference of FN binding to syndecan-4 12. TNC can also interact with cognate integrins on the surface of cells 13 (and references therein). Endothelial cells express TNC-binding integrin αvβ3 3. αvβ3 is upregulated in tumour-associated blood vessels where it has been found to play both pro-and anti-angiogenic roles in tumour angiogenesis, depending on the context 14. FN matrix assembly, or fibrillogenesis, is a complex process (reviewed in 15,16) driven by α5β1 integrin that takes place at specialized integrin-based structures called fibrillar adhesions at the cell-matrix interface
Published: 2017

18. Species composition and seasonal dynamics of aphid parasitoids and hyperparasitoids in wheat fields in northern China

Author: Mar Ferrer-Suay, Zhi-Wen Yao, Jesús Selfa, Vladimir Žikić, Lei Xu, Michael Traugott, Fan Yang, Yuyuan Guo, Juli Pujade-Villar, Željko Tomanović, Nicolas Desneux, Yue-Kun Wu, Qian Wang, Yanhui Lu, State Key Laboratory for Biology of Plant Diseases and Insect Pests, Chinese Academy of Agricultural Sciences (CAAS), University of Niš, University of Belgrade, Universitat de València (UV), Universitat Autònoma de Barcelona (UAB), University of Innsbruck, Institut Sophia Agrobiotech (ISA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), National Natural Science Foundation of China 31621064, Ministry of Education, Science and Technological Development of the Republic of Serbia III43001, European Project: 611810,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IRSES,APHIWEB(2014), Universitat de Barcelona, Leopold Franzens Universität Innsbruck - University of Innsbruck, Institut National de la Recherche Agronomique (INRA)-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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, [SPI.OTHER]Engineering Sciences [physics]/Other, Population Dynamics, Biodiversity, lcsh:Medicine, Control de plagues, interaction hôte parasitoïde, 01 natural sciences, Parasitoid, Blat, lcsh:Science, Triticum, Plant parasites, education.field_of_study, Aphid, Multidisciplinary, biology, période de croissance, Ecology, dynamique saisonnière, aphidius uzbekistanicus, puceron, hyperparasitoide, Wheat, Seasons, pachyneuron, China, Population, Parasitism, 010603 evolutionary biology, Article, Host-Parasite Interactions, Paràsits de les plantes, Species Specificity, Control of pests, medicine, Animals, education, chine, lcsh:R, Species diversity, Seasonality, biology.organism_classification, medicine.disease, 010602 entomology, champs, Agronomy, Aphids, Autre (Sciences de l'ingénieur), lcsh:Q
Abstract: Parasitoids are important natural enemies of aphids in wheat fields of northern China, and interest in them has increased in recent years. However, little is known regarding parasitoids of wheat aphids, which has hindered the study and understanding of aphid-parasitoid interactions. In the present study, three primary parasitoids and 15 hyperparasitoids were collected in wheat fields during a 2-year survey in northern China (2014, 2015) and a 2-year investigation at Langfang, Hebei Province (2015, 2016). Among them, Aphidius uzbekistanicus Luzhetski was found most frequently among the primary parasitoids, while Pachyneuron aphidis (Bouché) dominated the hyperparasitoid community. Investigation of the dynamics of wheat aphids and parasitoids revealed that the primary parasitoids appeared early in the growing period and that the hyperparasitoids appeared later. Analysis of the seasonal dynamics revealed that growth of the parasitoid population followed that of the aphid population and that the parasitism rates were highest in the late growing period.
Published: 2017

19. La dynamique récurrente de réseaux permet de réconcilier la segmentation et l’intégration du mouvement visuel

Author: Pierre Kornprobst, James Rankin, N. V. Kartheek Medathati, Guillaume S. Masson, Andrew Isaac Meso, Biologically plausible Integrative mOdels of the Visual system : towards synergIstic Solutions for visually-Impaired people and artificial visiON (BIOVISION), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Mathematical and Computational Neuroscience (NEUROMATHCOMP), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (JAD), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Bournemouth University [Poole] (BU), GSM and AIM are supported by a grant from the Agence Nationale de la Recherche (SPEED, ANR-13- SHS2–0006) and by the Centre National de la Recherche Scientifique. NVKM and PK were supported by the European Union Seventh Framework Programme (FP7/2007-2013, grant agreement n° 318723, MATHEMACS). JR was partially funded by a Swartz Foundation postdoc grant., ANR-13-BSH2-0006,SPEED,Traitement de la vitesse dans les scènes visuelles naturelles(2013), European Project: 318723,EC:FP7:ICT,FP7-ICT-2011-8,MATHEMACS(2012), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Kornprobst, Pierre, Blanc 2013 - Traitement de la vitesse dans les scènes visuelles naturelles - - SPEED2013 - ANR-13-BSH2-0006 - Blanc 2013 - VALID, MATHEmatics of Multi-level Anticipatory Complex Systems - MATHEMACS - - EC:FP7:ICT2012-10-01 - 2015-09-30 - 318723 - VALID, Mathématiques pour les Neurosciences (MATHNEURO), Center for Neural Science [New York] (CNS), New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Inria Sophia Antipolis, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (LJAD), College of Engineering, Mathematics and Physical Sciences [Exeter] (EMPS), University of Exeter, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Psychology [Bournemouth, UK] (Faculty of Science and Technology), and ANR-13-SHS2-0006,SPEED,Traitement de la vitesse dans les scènes visuelles naturelles
Subjects: Visual motion integration, Dynamical systems theory, Computer science, Models, Neurological, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], Motion Perception, [SCCO.COMP]Cognitive science/Computer science, [MATH.MATH-DS] Mathematics [math]/Dynamical Systems [math.DS], lcsh:Medicine, Sensory system, Systèmes dynamiques, 050105 experimental psychology, Motion (physics), Article, 03 medical and health sciences, Superposition principle, Motion, 0302 clinical medicine, direction selectivity, Animals, 0501 psychology and cognitive sciences, Computer vision, Segmentation, Motion perception, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Science, Network model, Neurons, Intégration du mouvement, Multidisciplinary, Quantitative Biology::Neurons and Cognition, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, [SCCO.NEUR] Cognitive science/Neuroscience, lcsh:R, Ring network, Pattern recognition, dynamical systems, Network dynamics, ring model, sélectivité à l’orientation, Macaca, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Q, Artificial intelligence, business, 030217 neurology & neurosurgery, Photic Stimulation
Abstract: In sensory systems, different computational rules are postulated to be implemented by different neuronal subpopulations, each one being characterised by a particular tuning function. For instance, in primate cortical area MT, different classes of direction-selective cells have been identified and related to either motion integration, segmentation or transparency. Still, how such different tuning properties are constructed is unclear. The dominant theoretical viewpoint postulates that differential weighting of MT inputs along the linear-nonlinear feedforward cascade is sufficient to build these different cell classes but it does not account for their complex temporal dynamics and their versatility when facing different input statistics. Here, we demonstrate that a recurrent network model of visual motion processing can reconcile these different properties. We show how excitatory and inhibitory recurrent connections, within a direction representation space, shape neuronal motion direction tuning and implement different computational rules such as vector averaging, winner-take-all or superposition. The model also captures ordered temporal transitions between these behaviours. In particular, depending on the inhibition regime the ring network can switch from motion integration to motion segmentation, thus being able to compute either a single pattern motion or to superpose multiple inputs as in motion transparency. We thus demonstrate that recurrent architectures can adaptively give rise to different cortical computational regimes depending upon the input statistics, thus reconciling the two facets of sensory processing: integration and segmentation.; Dans les systèmes sensoriels, différentes règles computationnelles sont supposées être implémentées par différentes sous-populations neuronales, chacune étant caractérisée par une fonction de sélectivité. Par exemple, dans la zone corticale des primates MT, différentes classes de cellules sélectives à la direction ont été identifiées et liées à l’intégration du mouvement, à la segmentation ou à la transparence. Cependant, la façon dont ces fonction de sélectivité sont construites n’est pas claire. Le point de vue théorique dominant postule que la pondération différentielle des entrées de MT le long de la cascade montante linéaire non linéaire est suffisante pour construire ces différentes classes de cellules, mais ne tient pas compte de leur dynamique temporelle complexe et leur versatilité face à différentes statistiques d’entrée. Ici, nous démontrons qu’un modèle de réseau récurrent de traitement du mouvement visuel peut réconcilier ces différentes propriétés. Nous montrons comment les connexions récurrentes excitatrices et inhibitrices, au sein d’un espace de représentation de direction, forment la sélectivité neuronale à la direction du mouvement et implémentent des règles de calcul différentes telles que la moyenne des vecteurs, le "tout au vainqueur" (winner-take-all) ou la superposition. Le modèle capture également les transitions temporelles ordonnées entre ces comportements. En particulier, en fonction du régime d’inhibition, le réseau en anneau (ring model) peut passer d’une intégration de mouvement à une segmentation de mouvement, ce qui permet de calculer soit un seul mouvement de motif, soit de superposer des entrées multiples comme dans les mouvements transparents. Nous démontrons ainsi que les architectures récurrentes peuvent adapter de façon adaptative des régimes de calculs corticaux différents en fonction des statistiques d’entrée, afin de réconcilier les deux facettes du traitement sensoriel: l’intégration et la segmentation.
Published: 2017

20. Altitude control in honeybees: joint vision-based learning and guidance

Author: Portelli, Geoffrey, Serres, Julien, Ruffier, Franck, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Behavior, Animal, Altitude, Flight, Animal, Science, Spatial Learning, Animals, Medicine, Bees, Vision, Ocular, Article, [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract: International audience; Studies on insects’ visual guidance systems have shed little light on how learning contributes to insects’ altitude control system. In this study, honeybees were trained to fly along a double-roofed tunnel after entering it near either the ceiling or the floor of the tunnel. The honeybees trained to hug the ceiling therefore encountered a sudden change in the tunnel configuration midways: i.e. a "dorsal ditch". Thus, the trained honeybees met a sudden increase in the distance to the ceiling, corresponding to a suddenstrong change in the visual cues available in their dorsal field of view. Honeybees reacted by rising quickly and hugging the new, higher ceiling, keeping a similar torward speed, distance to the ceiling and dorsal optic flow to those observed during the training step; whereas bees trained to follow the floor kept on following the floor regardless of the change in the ceiling height. When trained honeybees entered the tunnel via the other entry (the lower or upper entry) to that used during the training step, they quickly changed their altitude and hugged the surface they had previously learned to follow. These findings clearly show that trained honeybees control their altitude based on visual cues memorized during training. The memorized visual cues generated by the surfaces followed form a complex optic flow pattern: trained honeybees may attempt to match the visual cues they perceive with this memorized optic flow pattern by controlling their altitude.
Published: 2017

21. Threats to large brown algal forests in temperate seas: the overlooked role of native herbivorous fish

Author: Gianni, Fabrizio, Bartolini, Fabrizio, Pey, Alexis, Laurent, Mathieu, Martins, Gustavo M., Airoldi, Laura, Mangialajo, Luisa, Laboratoire d'océanographie de Villefranche (LOV), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecosystèmes Côtiers Marins et Réponses aux Stress (ECOMERS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre for Ecology - Evolution and Environmental Changes (cE3c) - Faculdade de Ciências, University of Lisbon, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Gianni, Fabrizio, Bartolini, Fabrizio, Pey, Alexi, Laurent, Mathieu, Martins, Gustavo M., Airoldi, Laura, Mangialajo, Luisa, Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Universidade de Lisboa = University of Lisbon (ULISBOA)
Subjects: Multidisciplinary, Science, Fishes, Biodiversity, Forests, Phaeophyta, Article, Mediterranean Sea, Animals, Medicine, Biomass, France, Herbivory, Ecosystem, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography
Abstract: International audience; Canopy-forming algae are declining globally due to multiple disturbances. This decline has recently been on the increase due to the spread of some tropical herbivorous fishes. This new phenomenon has drawn attention to the effects of fish herbivory in temperate areas, which have been assumed to be negligible compared to that of invertebrates, such as sea urchins. In this study, the impact of a Mediterranean native herbivorous fish (Sarpa salpa, salema) was assessed on the canopy-forming seaweed Cystoseira amentacea var. stricta. Cystoseira amentacea forms belts in the infralittoral fringe of wave-exposed shores, which has so far been considered a refuge from fish herbivory. To test the effects of salema feeding on natural C. amentacea belts, an innovative herbivore deterrent device was conceived. Salema had a significant effect on C. amentacea by decreasing algal size, biomass and fertility, by up to 97%. The results suggest that the contribution of salema feeding to the loss of Cystoseira forests in the Mediterranean may have been overlooked. In addition, the analysis of temporal and spatial patterns of salema landings in the Mediterranean Sea suggests that salema abundance may have increased recently. Thus, along with invertebrate herbivory and anthropogenic stressors, fish herbivory may also represent a potential threat to algal forests in temperate areas.
Published: 2017

22. EHD2 is a Predictive Biomarker of Chemotherapy Efficacy in Triple Negative Breast Carcinoma

Author: Sophie Vacher, Wei-Wei Shen, Anne Vincent-Salomon, Ivan Bièche, Laetitia Fuhrmann, Christophe Lamaze, Stéphanie Torrino, Membrane Dynamics and Mechanics of Intracellular Signaling team [Paris], Institut Curie [Paris]-Université Paris sciences et lettres (PSL), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC), Pharmacogenomics Unit [Paris], Department of Genetics [Paris], Institut Curie [Paris]-Institut Curie [Paris], Department of Pathology [Paris], Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), The Johannes and Lamaze teams, the PICT-IBiSA/Nikon Imaging Centre at Institut Curie-CNRS and the France-BioImaging infrastructure are members of Labex Cell(n)Scale (N° ANR-11-LBX-0038) and of IDEX PSL (N° ANR-10-IDEX-0001-02 PSL)., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Bodescot, Myriam, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Institut Curie [Paris]-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 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: Oncology, medicine.medical_treatment, lcsh:Medicine, Triple Negative Breast Neoplasms, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 0302 clinical medicine, Breast cancer, Caveolae, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, lcsh:Science, Triple-negative breast cancer, Cancer, 0303 health sciences, Multidisciplinary, Predictive marker, Middle Aged, Prognosis, Immunohistochemistry, 3. Good health, Gene Expression Regulation, Neoplastic, Cytokine, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Triple-Negative Breast Carcinoma, Female, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, 030304 developmental biology, Aged, Neoplasm Staging, Chemotherapy, business.industry, lcsh:R, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, lcsh:Q, Neoplasm Grading, business, Carrier Proteins
Abstract: EHD2 is a mechanotransducing ATPase localized in caveolae invaginations at the plasma membrane. EHD2 has recently been associated with several human cancers, however the significance of EHD2 transcript levels in cancer prognosis remains debated. Breast cancer is the most commonly occurring cancer in women and prognosis is variable depending on the subtypes. Triple negative breast cancer (TNBC) often has a poor therapeutic response. The aim of this study was to assess the prognostic significance of EHD2 transcripts and protein expression levels in breast carcinomas. We found that low EHD2 levels were associated with enhanced proliferation, migration and invasion of TNBC cells. EHD2 expression was significantly reduced in TNBC tissues and the loss of EHD2 led to higher expression of the pro-tumoral cytokine IL-8. In apparent contradiction with in vitro data, multivariate analysis of two independent cohorts of breast cancer patients revealed that low EHD2 was in fact associated with good prognosis in the highly proliferative TNBC subtype. Accordingly, TNBC low EHD2 expressers were found to benefit the most from chemotherapy when compared to all subtypes of breast cancers. Our study validates EHD2 expression level as an independent prognostic factor of metastasis-free survival and as a new predictive marker of chemotherapy efficacy in TNBC patients.
Published: 2019

23. The C-terminal domain of EFA6A interacts directly with F-actin and assembles F-actin bundles

Author: Eric Macia, Hong Wang, Sandra Lacas-Gervais, Frédéric Luton, Michel Franco, Mariagrazia Partisani, Christophe Le Clainche, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), 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), Centre Commun de Microscopie Appliquée (CCMA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), This work is supported by the Centre National de la Recherche Scientifique, the Association pour la Recherche sur le Cancer and the Agence Nationale pour la Recherche through the Investissement pour le Futur Labex Signalife Program ref ANR-11Labx-0028-01. H W is supported by a Ph.D. fellowship from the China Scholarship Council (CSC). CLC is supported by the Agence Nationale pour la Recherche Grants ANR-16-CE13- 0007-02 PHAGOMECANO., We thank J. P. Laugier (CCMA-UCA Nice) for SEM imaging and Dr. M.F. Carlier for preliminary experiments and helpful discussions. We kindly thank Dr Sylvain Bourgoin for providing us with monoclonal anti-Arf6., 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and ANR-16-CE13-0007,PHAGOMECANO,Mécanotransduction associée à la phagocytose dépendante des intégrines(2016)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Endocytic cycle, lcsh:Medicine, macromolecular substances, Article, Protein filament, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Guanine Nucleotide Exchange Factors, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:Science, Actin, Cytoskeleton, Epithelial polarity, Neurons, Multidisciplinary, Chemistry, C-terminus, lcsh:R, Cell Membrane, Cell Polarity, Proteins, Actin cytoskeleton, In vitro, Actins, Cell biology, Actin Cytoskeleton, 030104 developmental biology, lcsh:Q, 030217 neurology & neurosurgery, Function (biology)
Abstract: The Arf6-specific exchange factor EFA6 is involved in the endocytic/recycling pathway for different cargos. In addition EFA6 acts as a powerful actin cytoskeleton organizer, a function required for its role in the establishment of the epithelial cell polarity and in neuronal morphogenesis. We previously showed that the C-terminus of EFA6 (EFA6-Ct) is the main domain which contributes to actin reorganization. Here, by in vitro and in vivo experiments, we sought to decipher, at the molecular level, how EFA6 controls the dynamic and structuring of actin filaments. We showed that EFA6-Ct interferes with actin polymerization by interacting with and capping actin filament barbed ends. Further, in the presence of actin mono-filaments, the addition of EFA6-Ct triggered the formation of actin bundles. In cells, when the EFA6-Ct was directed to the plasma membrane, as is the case for the full-length protein, its expression induced the formation of membrane protrusions enriched in actin cables. Collectively our data explain, at least in part, how EFA6 plays an essential role in actin organization by interacting with and bundling F-actin.
Published: 2019

24. Improved drought stress tolerance in Arabidopsis by CRISPR/dCas9 fusion with a Histone AcetylTransferase

Author: Janice de Almeida-Engler, Daniel D. Noriega, Joaquin Felipe Roca Paixão, Isabela Tristan Lourenço-Tessutti, Caroline Bournaud, Thuanne Pires Ribeiro, François-Xavier Gillet, Maria Fatima Grossi-de-Sa, Bruno Paes de Melo, Bournaud, Caroline, Réponse des Organismes aux Stress Environnementaux (ROSE), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Empresa Brasileira de Pesquisa Agropecuária (Embrapa), Ministério da Agricultura, Pecuária e Abastecimento [Brasil] (MAPA), Governo do Brasil-Governo do Brasil, Université de Nice Sophia-Antipolis (UNSA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Universidade Católica de Brasília (UCB), CAPES-COFEUB [Sv.622/18], JOAQUIN FELIPE ROCA PAIXÃO, INRA, UNIVERSITÉ CÔTE D’AZUR, FRANCE, MARIA FATIMA GROSSI DE SA, Cenargen., FRANÇOIS-XAVIER GILLET, THUANNE PIRES RIBEIRO, CAROLINE BOURNAUD, ISABELA TRISTAN LOURENCO TESSUTTI, Cenargen, DANIEL D. NORIEGA, BRUNO PAES DE MELO, and JANICE DE ALMEIDA-ENGLER, INRA, UNIVERSITÉ CÔTE D’AZUR, FRANCE
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Acclimatization, Arabidopsis, lcsh:Medicine, Molecular engineering in plants, Genetically modified crops, chemistry.chemical_compound, 0302 clinical medicine, Gene Expression Regulation, Plant, CRISPR-Associated Protein 9, Gene expression, lcsh:Science, Promoter Regions, Genetic, Abscisic acid, transcription factor, Histone Acetyltransferases, 2. Zero hunger, Regulation of gene expression, Multidisciplinary, biology, food and beverages, Plants, Genetically Modified, Cell biology, Droughts, Basic-Leucine Zipper Transcription Factors, RNA polymerase, climate-change, [SDE]Environmental Sciences, areb1, Recombinant Fusion Proteins, Drought tolerance, Chromatin remodelling, Article, 03 medical and health sciences, aba, Gene, Reporter gene, Arabidopsis Proteins, lcsh:R, fungi, biology.organism_classification, 030104 developmental biology, chemistry, lcsh:Q, CRISPR-Cas Systems, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Drought episodes decrease plant growth and productivity, which in turn cause high economic losses. Plants naturally sense and respond to water stress by activating specific signalling pathways leading to physiological and developmental adaptations. Genetically engineering genes that belong to these pathways might improve the drought tolerance of plants. The abscisic acid (ABA)-responsive element binding protein 1/ABRE binding factor (AREB1/ABF2) is a key positive regulator of the drought stress response. We investigated whether the CRISPR activation (CRISPRa) system that targets AREB1 might contribute to improve drought stress tolerance in Arabidopsis. Arabidopsis histone acetyltransferase 1 (AtHAT1) promotes gene expression activation by switching chromatin to a relaxed state. Stable transgenic plants expressing chimeric dCas9HAT were first generated. Then, we showed that the CRISPRa dCas9HAT mechanism increased the promoter activity controlling the β-glucuronidase (GUS) reporter gene. To activate the endogenous promoter of AREB1, the CRISPRa dCas9HAT system was set up, and resultant plants showed a dwarf phenotype. Our qRT-PCR experiments indicated that both AREB1 and RD29A, a gene positively regulated by AREB1, exhibited higher gene expression than the control plants. The plants generated here showed higher chlorophyll content and faster stomatal aperture under water deficit, in addition to a better survival rate after drought stress. Altogether, we report that CRISPRa dCas9HAT is a valuable biotechnological tool to improve drought stress tolerance through the positive regulation of AREB1.
Published: 2019

25. Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs visceral endoderm endocytosis and endodermal patterning in the mouse

Author: Vincent Lelievre, Olivier Cases, Jérôme Collignon, Anna-Katerina Hadjantonakis, Renata Kozyraki, Aitana Perea-Gomez, Maria V. Pulina, Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Memorial Sloane Kettering Cancer Center [New York], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), 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), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Rockefeller University [New York], Gestionnaire, Hal Sorbonne Université, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Intrinsic Factor, Cell signaling, Embryology, [SDV]Life Sciences [q-bio], Endocytic cycle, lcsh:Medicine, Embryonic Development, Receptors, Cell Surface, Biology, Endocytosis, Article, Mesoderm, 03 medical and health sciences, Mice, 0302 clinical medicine, Pregnancy, medicine, Animals, lcsh:Science, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Multidisciplinary, lcsh:R, Embryogenesis, Endoderm, Gastrulation, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Biological Transport, Cell Differentiation, Cubilin, Embryonic stem cell, Cell biology, Mice, Inbred C57BL, Protein Transport, Vitamin B 12, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, 030104 developmental biology, medicine.anatomical_structure, embryonic structures, lcsh:Q, Female, Carrier Proteins, 030217 neurology & neurosurgery
Abstract: The visceral endoderm is a polarized epithelial monolayer necessary for early embryonic development in rodents. A key feature of this epithelium is an active endocytosis and degradation of maternal nutrients, in addition to being the source of various signaling molecules or inhibitors required for the differentiation and patterning of adjacent embryonic tissues. Endocytosis across the visceral endoderm epithelium involves specific cell surface receptors and an extensive sub-membrane vesicular system with numerous apical vacuoles/lysosomes. We previously reported that Cubilin, the endocytic receptor for intrinsic factor-vitamin B12, albumin and apolipoproteinA-I/HDL allows maternal nutrient uptake by the visceral endoderm. In the present study, we show that the germline ablation of Cubilin impairs endodermal and mesodermal patterning, and results in developmental arrest at gastrulation. Notably, visceral endoderm dispersal is impeded in Cubilin null embryos. We further confirm the essential role of Cubilin in nutrient internalization by the early visceral endoderm and highlight its involvement in the formation of apical vacuoles. Our results reveal essential roles for Cubilin in early embryonic development, and suggest that in addition to its nutritive function, Cubilin sustains signaling pathways involved in embryonic differentiation and patterning.
Published: 2019

26. Subfossil trees suggest enhanced Mediterranean hydroclimate variability at the onset of the Younger Dryas

Author: Pauly, Maren, Helle, Gerhard, Miramont, Cécile, Büntgen, Ulf, Treydte, Kerstin, Reinig, Frederick, Guibal, Frédéric, Sivan, Olivier, Heinrich, Ingo, Riedel, Frank, Kromer, Bernd, Balanzategui, Daniel, Wacker, Lukas, Sookdeo, Adam, Brauer, Achim, German Research Centre for Geosciences - Helmholtz-Centre Potsdam (GFZ), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Swiss Federal Institute for Forest, Snow and Landscape Research WSL, Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut national de recherches archéologiques préventives (Inrap), University of Johannesburg [South Africa] (UJ), Institute of Environmental Physics [Heidelberg] (IUP), Universität Heidelberg [Heidelberg] = Heidelberg University, Institute for Particle Physics and Astrophysics [ETH Zürich] (IPA), Department of Physics [ETH Zürich] (D-PHYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), GeoForschungsZentrum - Helmholtz-Zentrum Potsdam (GFZ), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), University of Johannesburg (UJ), Universität Heidelberg [Heidelberg], Swiss Federal Institute for Forest, Snow and Avalanche Research WSL, Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institute for Particle Physics, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)
Subjects: Geologic Sediments, Atmospheric chemistry, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Fossils, Mediterranean Region, Climate Change, education, lcsh:R, Radiometric Dating, Temperature, lcsh:Medicine, Oxygen Isotopes, Palaeoclimate, Trees, Geochemistry, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, [SDE]Environmental Sciences, ddc:550, lcsh:Q, ddc:500, Institut für Geowissenschaften, Mathematisch-Naturwissenschaftliche Fakultät, lcsh:Science, ddc:600, health care economics and organizations
Abstract: International audience; Nearly 13,000 years ago, the warming trend into the Holocene was sharply interrupted by a reversal to near glacial conditions. Climatic causes and ecological consequences of the Younger Dryas (YD) have been extensively studied, however proxy archives from the Mediterranean basin capturing this period are scarce and do not provide annual resolution. Here, we report a hydroclimatic reconstruction from stable isotopes (δ 18 O, δ 13 C) in subfossil pines from southern France. Growing before and during the transition period into the YD (12 900-12 600 cal BP), the trees provide an annually resolved, continuous sequence of atmospheric change. Isotopic signature of tree sourcewater (δ 18 O sw) and estimates of relative air humidity were reconstructed as a proxy for variations in air mass origin and precipitation regime. We find a distinct increase in inter-annual variability of sourcewater isotopes (δ 18 O sw), with three major downturn phases of increasing magnitude beginning at 12 740 cal BP. The observed variation most likely results from an amplified intensity of North Atlantic (low δ 18 O sw) versus Mediterranean (high δ 18 O sw) precipitation. This marked pattern of climate variability is not seen in records from higher latitudes and is likely a consequence of atmospheric circulation oscillations at the margin of the southward moving polar front. During the abrupt and intense climate change from the Allerød warm phase to the YD cold reversal in the North Hemisphere (ca. 12 700-11 600 cal BP) 1,2 sea-ice production and drifting enhanced 3 , alpine glaciers advanced 4 , storm intensity strengthened 5 , and a reorganization of the atmosphere 6,7 may have occurred. Greenland ice core data (NGRIP) reveal temperature drops of 10-15 °C with simultaneous reductions in snow accumulation and amplifications in atmospheric dust within less than a decade 6,8. During the rapid cooling, lake sediment records across Europe signal intensified wind stress, aridity and detrital input, alongside drastic ecological changes 5,9,10. The results are spatially heterogeneous in terms of hydrological change, as other European lake records find more humid conditions and/or increased quantity and intensity of precipitation (associated with higher lake levels in certain cases) 11,12. Model simulations constrained by proxy data indicate no single factor could cause the observed YD cold reversal, but rather a complex combination of weakened Atlantic meridional overturning circulation (AMOC), altered atmospheric circulation patterns, and moderate negative radiative forcing as most plausible driving factors 13. Nevertheless, mechanisms of climate variability in the North Atlantic region remain under intense debate 8 , even for the most recent past 14 .
Published: 2018

27. Acute and long-term cardioprotective effects of the Traditional Chinese Medicine MLC901 against myocardial ischemia-reperfusion injury in mice

Author: Christophe Piot, Catherine Heurteaux, Soulit Thoumala, Joël Nargeot, Christian Barrère, Laura Gallot, Anne Vincent, Michel Lazdunski, Stéphanie Barrère-Lemaire, Aurélie Covinhes, Institut de Génomique Fonctionnelle (IGF), 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), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), 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)-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), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), 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)-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), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Vincent, Anne
Subjects: Male, [SDV]Life Sciences [q-bio], Myocardial Infarction, lcsh:Medicine, 030204 cardiovascular system & hematology, Mice, 0302 clinical medicine, Fibrosis, Troponin I, Medicine, Chinese Traditional, lcsh:Science, Extracellular Signal-Regulated MAP Kinases, Cardioprotection, Multidisciplinary, Cerebral infarction, Heart, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Oncogene Protein v-akt, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, cardioprotection, Reperfusion Injury, Cardiology, Signal Transduction, medicine.medical_specialty, traditional chinese medecine, Article, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, In vivo, Internal medicine, Heart rate, medicine, ischemia reperfusion, Animals, Humans, business.industry, Myocardium, lcsh:R, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Regional Blood Flow, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, lcsh:Q, business, Reperfusion injury, 030217 neurology & neurosurgery, Ex vivo, Drugs, Chinese Herbal
Abstract: MLC901, a traditional Chinese medicine containing a cocktail of active molecules, both reduces cerebral infarction and improves recovery in patients with ischemic stroke. The aim of this study was to evaluate the acute and long-term benefits of MLC901 in ischemic and reperfused mouse hearts. Ex vivo, under physiological conditions, MLC901 did not show any modification in heart rate and contraction amplitude. However, upon an ischemic insult, MLC901 administration during reperfusion, improved coronary flow in perfused hearts. In vivo, MLC901 (4 µg/kg) intravenous injection 5 minutes before reperfusion provided a decrease in both infarct size (49.8%) and apoptosis (49.9%) after 1 hour of reperfusion. Akt and ERK1/2 survival pathways were significantly activated in the myocardium of those mice. In the 4-month clinical follow-up upon an additional continuous per os administration, MLC901 treatment decreased cardiac injury as revealed by a 45%-decrease in cTnI plasmatic concentrations and an improved cardiac performance assessed by echocardiography. A histological analysis revealed a 64%-decreased residual scar fibrosis and a 44%-increased vascular density in the infarct region. This paper demonstrates that MLC901 treatment was able to provide acute and long-term cardioprotective effects in a murine model of myocardial ischemia-reperfusion injury in vivo.
Published: 2017

28. Implication of REDD1 in the activation of inflammatory pathways

Author: Mireille Cormont, Faustine Pastor, Claire Regazzetti, Sophie Giorgetti-Peraldi, Noémie Druelle, Karine Dumas, Pascal Peraldi, Jean-François Tanti, Marie-Astrid Barthélémy, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Valrose (IBV), 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre méditérannéen de médecine moléculaire (C3M), 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), and ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Lipopolysaccharide, Science, Adipose tissue macrophages, Adipose tissue, Inflammation, mTORC1, Biology, Article, Proinflammatory cytokine, Mice, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, medicine, Animals, ComputingMilieux_MISCELLANEOUS, Epididymis, Mice, Knockout, Multidisciplinary, Macrophages, Inflammasome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Endotoxins, 030104 developmental biology, Endocrinology, Adipose Tissue, chemistry, Cytokines, Medicine, Tumor necrosis factor alpha, medicine.symptom, Transcription Factors, medicine.drug
Abstract: In response to endotoxemia, the organism triggers an inflammatory response, and the visceral adipose tissue represents a major source of proinflammatory cytokines. The regulation of inflammation response in the adipose tissue is thus of crucial importance. We demonstrated that Regulated in development and DNA damage response-1 (REDD1) is involved in inflammation. REDD1 expression was increased in response to lipopolysaccharide (LPS) in bone marrow derived macrophages (BMDM) and in epidydimal adipose tissue. Loss of REDD1 protected the development of inflammation, since the expression of proinflammatory cytokines (TNFα, IL-6, IL-1β) was decreased in adipose tissue of REDD1−/− mice injected with LPS compared to wild-type mice. This decrease was associated with an inhibition of the activation of p38MAPK, JNK, NF-κB and NLRP3 inflammasome leading to a reduction of IL-1β secretion in response to LPS and ATP in REDD1−/− BMDM. Although REDD1 is an inhibitor of mTORC1, loss of REDD1 decreased inflammation independently of mTORC1 activation but more likely through oxidative stress regulation. Absence of REDD1 decreases ROS associated with a dysregulation of Nox-1 and GPx3 expression. Absence of REDD1 in macrophages decreases the development of insulin resistance in adipocyte-macrophage coculture. Altogether, REDD1 appears to be a key player in the control of inflammation.
Published: 2017

29. New dating evidence of the early presence of hominins in Southern Europe

Author: Michel, Véronique, Chou, Chuan-Chou, Woodhead, Jon, Hu, Hsun-Ming, Wu, Chung-Che, Moullé, Pierre-Élie, Khatib, Samir, Cauche, Dominique, Moncel, Marie-Hélène, Valensi, Patricia, Chou, Yu-Min, Gallet, Sylvain, Echassoux, Anna, Orange, François, De Lumley, Henry, Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Géoazur (GEOAZUR 7329), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), High-Precision Mass Spectrometry and Environment Change Laboratory (HISPEC), National Taiwan University [Taiwan] (NTU), School of Earth Sciences [Melbourne], Faculty of Science [Melbourne], University of Melbourne-University of Melbourne, Musée de Préhistoire Régionale de Menton, Centre National de la Recherche Scientifique (CNRS), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université de Perpignan Via Domitia (UPVD), Laboratoire de Préhistoire Nice-Côte d’Azur, Institut de Paléontologie Humaine (IPH), Fondation I.P.H-Centre National de la Recherche Scientifique (CNRS), Center of Marine Magnetism, Department of Ocean Science and Engineering, Laboratoire Départemental de Préhistoire du Lazaret (LDPL), Département des Alpes-Maritimes, Centre Commun de Microscopie Appliquée (CCMA), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Muséum d'Histoire Naturelle, Institut de Paléontologie Humaine, Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD), Musée de Préhistoire de Tourrette-Levens, Laboratoire Géosciences et Environnement Cergy (GEC), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: Mammals, Geologic Sediments, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Fossils, Human Migration, lcsh:R, Radiometric Dating, lcsh:Medicine, Hominidae, Georgia (Republic), Article, Bone and Bones, Caves, Archaeology, Lead, Africa, Animals, Humans, Uranium, lcsh:Q, France, lcsh:Science, ComputingMilieux_MISCELLANEOUS, History, Ancient
Abstract: The first “Out of Africa” migrations represent a seminal event in the history of humankind. At the gates of Europe, the first appearance of Hominins is recorded in Georgia, 1.8 million years ago (Ma); however, the picture of migration across the continent remains incomplete. Vallonnet Cave (France) is a Lower Paleolithic prehistoric site with traces of hominin activities including lithic remains and cut-marks on mammal bones. Here, we apply the uranium-lead (U-Pb) methods to two flowstones to date the intervening archaeological levels. The U-Pb data, coupled with paleomagnetic constraints, provide an age range from 1.2 to 1.1 Ma. The results conclusively demonstrate that Vallonnet Cave is one of the oldest European prehistoric sites in France with early hominin occupations associated with an Epivillafranchian fauna. Combined with data from other archaeological sites, the new precise chronology suggests a widespread occupation the Northern Mediterranean to Southwestern Europe at ~1.2 Ma.
Published: 2017

30. Prediction of miRNA-disease Associations using an Evolutionary Tuned Latent Semantic Analysis

Author: Pallez, Denis, Gardès, Julien, Pasquier, Claude, Scalable and Pervasive softwARe and Knowledge Systems (Laboratoire I3S - SPARKS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and BIOMANDA
Subjects: Models, Genetic, lcsh:R, Predictive medicine, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], Sensitivity and Specificity, Article, MicroRNAs, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Machine learning, Cancer genomics, Humans, lcsh:Q, [INFO]Computer Science [cs], Genetic Predisposition to Disease, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], lcsh:Science, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Algorithms
Abstract: International audience; MicroRNAs, small non-coding elements implied in gene regulation, are very interesting biomarkers for various diseases such as cancers. They represent potential prodigious biotechnologies for early diagnosis and gene therapies. However, experimental verification of microRNA-disease associations are time-consuming and costly, so that computational modeling is a proper solution. Previously, we designed MiRAI, a predictive method based on distributional semantics, to identify new associations between microRNA molecules and human diseases. Our preliminary results showed very good prediction scores compared to other available methods. However, MiRAI performances depend on numerous parameters that cannot be tuned manually. In this study, a parallel evolutionary algorithm is proposed for finding an optimal configuration of our predictive method. The automatically parametrized version of MiRAI achieved excellent performance. It highlighted new miRNA-disease associations, especially the potential implication of mir-188 and mir-795 in various diseases. In addition, our method allowed to detect several putative false associations contained in the reference database.
Published: 2017

31. Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation

Author: Emilie Andrio, Emmanuel Lemichez, Jacqueline Cherfils, Poul H. Sorensen, Anne Doye, Daniel Hamaoui, Mads Daugaard, Raymond Ruimy, Frédéric Bost, Amel Mettouchi, Romain Lotte, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toxines bactériennes dans la relation hôtes-pathogènes, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Laboratoire de Bactériologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital Archet 2 [Nice] (CHU), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), University of British Columbia (UBC), Vancouver Prostate Centre [Vancouver General Hospital] (VPC), Vancouver General Hospital, BC Cancer Agency Research Centre (BCCRC), Signalisation moléculaire et obésité, 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), This work was supported by INSERM, CNRS and fundings from the Ligue Nationale Contre le Cancer (LNCC, équipe labellisée), Association pour la Recherche sur le Cancer (ARC-SFI20111203659 & ARC-SFI20111203671), a fellowship LNCC to D.H., a PhD fellowship from the 'Fondation pour la Recherche Médicale' (FRM-FDM20150632804) to R.L., We are grateful to Melissa Sivaneson, Frédéric Reinier and Patrick Munro for technical help and fruitful discussions. We thank Orane Visvikis for critical reading of the manuscript., 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)-Université Côte d'Azur (UCA), 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: Models, Molecular, rac1 GTP-Binding Protein, 0301 basic medicine, HECT domain, MESH: Ubiquitin-Protein Ligases/chemistry, Somatic cell, [SDV]Life Sciences [q-bio], MESH: Amino Acid Sequence, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Structure-Activity Relationship, Ubiquitin, Neoplasms, MESH: Ubiquitin-Protein Ligases/genetics, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Ubiquitin-Protein Ligases/metabolism, Ankyrin, Small GTPase, Genetics, chemistry.chemical_classification, Multidisciplinary, biology, 3. Good health, Ubiquitin ligase, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Protein Domains, MESH: Models, Molecular, Protein Binding, MESH: rac1 GTP-Binding Protein/metabolism, MESH: Mutant Proteins/chemistry, Ubiquitin-Protein Ligases, Protein domain, Mutation, Missense, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, Cell Line, MESH: Mutation, Missense/genetics, Structure-Activity Relationship, 03 medical and health sciences, Protein Domains, MESH: Neoplasms/genetics, MESH: Cell Proliferation, Humans, MESH: Protein Binding, Amino Acid Sequence, Cell Proliferation, MESH: Humans, Cell growth, Ubiquitination, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Cell Line, 030104 developmental biology, chemistry, Proteolysis, biology.protein, Mutant Proteins, MESH: Ubiquitination
Abstract: The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation. In addition, several mutations located in the ankyrin domain displayed a dramatic reduction in Rac1 ubiquitylation associated with a decrease of colony formation in soft agar. 3D structure modelling of the 7 ankyrin-repeats coupled to functional analysis identified a surface epitope centered on one of the mutated residue, Gly-175, which is critical for controlling Rac1 binding and ubiquitylation. We also identified a role for the MID domain in conferring the specificity of association of HACE1 to the active form of Rac1. Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation.
Published: 2017

32. Acclimation of a low iron adapted Ostreococcus strain to iron limitation through cell biomass lowering

Author: Botebol, Hugo, Lelandais, Gaelle, Six, Christophe, Lesuisse, Emmanuel, Meng, Arnaud, Bittner, Lucie, Lecrom, Stéphane, Sutak, Robert, Lozano, Jean-Claude, Schatt, Philippe, Vergé, Valérie, Blain, Stéphane, Bouget, François-Yves, Laboratoire d'Océanographie Microbienne (LOMIC), Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), MArine Phototrophic Prokaryotes (MAPP), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Analyse des Données à Haut Débit en Génomique (ADHDG), Evolution Paris Seine, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC), Charles University [Prague] (CU), Procaryotes Phototrophes Marins = MArine Phototrophic Prokaryotes (MAPP), Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Adaptation et diversité en milieu marin (ADMM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Systématique, adaptation, évolution (SAE), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Evolution Paris Seine, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Université des Antilles et de la Guyane (UAG), and Charles University [Prague]
Subjects: Chlorophyta, Science, Acclimatization, Gene Expression Profiling, Iron, Medicine, Biomass, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, Article, Trace Elements
Abstract: International audience; Iron is an essential micronutrient involved in many biological processes and is often limiting for primary production in large regions of the World Ocean. Metagenomic and physiological studies have identified clades or ecotypes of marine phytoplankton that are specialized in iron depleted ecological niches. Although less studied, eukaryotic picophytoplankton does contribute significantly to primary production and carbon transfer to higher trophic levels. In particular, metagenomic studies of the green picoalga Ostreococcus have revealed the occurrence of two main clades distributed along coast-offshore gradients, suggesting niche partitioning in different nutrient regimes. Here, we present a study of the response to iron limitation of four Ostreococcus strains isolated from contrasted environments. Whereas the strains isolated in nutrient-rich waters showed high iron requirements, the oceanic strains could cope with lower iron concentrations. The RCC802 strain, in particular, was able to maintain high growth rate at low iron levels. Together physiological and transcriptomic data indicate that the competitiveness of RCC802 under iron limitation is related to a lowering of iron needs though a reduction of the photosynthetic machinery and of protein content, rather than to cell size reduction. Our results overall suggest that iron is one of the factors driving the differentiation of physiologically specialized Ostreococcus strains in the ocean.
Published: 2017

33. Eμ and 3′RR IgH enhancers show hierarchic unilateral dependence in mature B-cells

Author: Saintamand, Alexis, Vincent-Fabert, Christelle, Marquet, Marie, Ghazzaui, Nour, Magnone, Virginie, Pinaud, Eric, Cogné, Michel, Denizot, Yves, Chard-Hutchinson, Xavier, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), and ANR-16-CE12-0017,EpiSwitch-3RR,Dissection génétique et fonctionnelle du rôle de la région de contrôle du locus IgH au cours de la commutation isotypique(2016)
Subjects: Male, B-Lymphocytes, Transcription, Genetic, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Differentiation, Immunoglobulin Class Switching, Article, Epigenesis, Genetic, Mice, Enhancer Elements, Genetic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, Animals, Female, Immunoglobulin Heavy Chains
Abstract: International audience; Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene cluster: the 5'Eμ super-enhancer promotes VDJ recombination during the earliest steps of B-cell ontogeny while the 3' regulatory region (3'RR) is essential for late differentiation. Since they carry functional synergies in mature B-cells and physically interact during IgH locus DNA looping, we investigated if they were independent engines of locus remodelling or if their function was more intimately intermingled, their optimal activation then requiring physical contact with each other. Analysis of chromatin marks, enhancer RNA transcription and accessibility in Eμ- and 3'RR-deficient mice show, in mature activated B-cells, an unilateral dependence of this pair of enhancers: while the 3'RR acts in autonomy, Eμ in contrast likely falls under control of the 3'RR.
Published: 2017

34. Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase

Author: Julie Poulain, Maya Belghazi, Dominique Colinet, Carole Dossat, Marc Ravallec, Marylène Poirié, Hugo Mathé-Hubert, Jean-Luc Gatti, Emeline Deleury, Institut Sophia Agrobiotech (ISA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier] (DGIMI), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), 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 Paris-Saclay, ANR-09-BLAN-0243-01, ANR-11-LABX-0028, ANR-09-BLAN-0243,PARATOXOSE(2009), Institut National de la Recherche Agronomique (INRA)-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)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Mathé Hubert, Hugo, Colinet, Dominique, Poirié, Marylène, Gatti, Jean-Luc, Enjalbert, Alain, and Blanc - - PARATOXOSE2009 - ANR-09-BLAN-0243 - Blanc - VALID
Subjects: 0301 basic medicine, Proteome, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, media_common.quotation_subject, Olive fruit fly, Wasps, Parasitism, Venom, Wasp Venoms, Insect, Leptopilina, Leucine-Rich Repeat Proteins, Article, Parasitoid, 03 medical and health sciences, South Africa, pachyneuron concolor, Botany, protéine du venin, Animals, media_common, psyttalia lounsburyi, Multidisciplinary, 030102 biochemistry & molecular biology, biology, Host (biology), beta-Glucosidase, fungi, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Proteins, Figitidae, biology.organism_classification, Kenya, 030104 developmental biology, Insect Proteins
Abstract: Venom composition of parasitoid wasps attracts increasing interest – notably molecules ensuring parasitism success on arthropod pests – but its variation within and among taxa is not yet understood. We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. concolor, olive fruit fly parasitoids that differ in host range. Among the shared abundant proteins, we found a GH1 β-glucosidase and a family of leucine-rich repeat (LRR) proteins. Olive is extremely rich in glycoside compounds that are hydrolyzed by β-glucosidases into defensive toxic products in response to phytophagous insect attacks. Assuming that Psyttalia host larvae sequester ingested glycosides, the injected venom GH1 β-glucosidase could induce the release of toxic compounds, thus participating in parasitism success by weakening the host. Venom LRR proteins are similar to truncated Toll-like receptors and may possibly scavenge the host immunity. The abundance of one of these LRR proteins in the venom of only one of the two P. lounsburyi strains evidences intraspecific variation in venom composition. Altogether, venom intra- and inter-specific variation in Psyttalia spp. were much lower than previously reported in the Leptopilina genus (Figitidae), suggesting it might depend upon the parasitoid taxa.
Published: 2016

35. Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity

Author: Kran Suknuntha, Pascal Peraldi, Annie Ladoux, Xi Yao, Phi Villageois, Anne-Laure Hafner, Karima Annab, Bernard Binétruy, Christophe Ravaud, Igor I. Slukvin, Julian Contet, Christian Dani, Institut de Biologie Valrose (IBV), 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), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, animal structures, Induced Pluripotent Stem Cells, PAX3, Gene Expression, Adipose tissue, Ascorbic Acid, Dioxoles, Biology, Iodide Peroxidase, complex mixtures, ZIC1, Article, Cell Line, Tumor Necrosis Factor Receptor Superfamily, Member 9, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Transforming Growth Factor beta, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Adipocyte, polycyclic compounds, Humans, Progenitor cell, PAX3 Transcription Factor, Multidisciplinary, Epidermal Growth Factor, CD137, Cell Differentiation, Ascorbic acid, 3. Good health, Cell biology, Adipocytes, Brown, 030104 developmental biology, chemistry, Biochemistry, Adipogenesis, Benzamides, embryonic structures, Apoptosis Regulatory Proteins, Biomarkers, 030217 neurology & neurosurgery, Signal Transduction, Transcription Factors
Abstract: Human induced pluripotent stem cells (hiPSCs) show great promise for obesity treatment as they represent an unlimited source of brown/brite adipose progenitors (BAPs). However, hiPSC-BAPs display a low adipogenic capacity compared to adult-BAPs when maintained in a traditional adipogenic cocktail. The reasons of this feature are unknown and hamper their use both in cell-based therapy and basic research. Here we show that treatment with TGFβ pathway inhibitor SB431542 together with ascorbic acid and EGF were required to promote hiPSCs-BAP differentiation at a level similar to adult-BAP differentiation. hiPSC-BAPs expressed the molecular identity of adult-UCP1 expressing cells (PAX3, CIDEA, DIO2) with both brown (ZIC1) and brite (CD137) adipocyte markers. Altogether, these data highlighted the critical role of TGFβ pathway in switching off hiPSC-brown adipogenesis and revealed novel factors to unlock their differentiation. As hiPSC-BAPs display similarities with adult-BAPs, it opens new opportunities to develop alternative strategies to counteract obesity.
Published: 2016

36. Spherulization as a process for the exudation of chemical cues by the encrusting sponge C. crambe

Author: Marcelino T. Suzuki, Julie Croué, Olivier P. Thomas, Eva Ternon, Rémi Dumollard, Sandrine Chenesseau, Lina Zarate, Institut de Chimie de Nice (ICN), 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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-PIERRE FABRE-EDF (EDF)-Centre National de la Recherche Scientifique (CNRS), National University of Ireland [Galway] (NUI Galway), Géoazur (GEOAZUR 7329), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Chimie de Nice ( ICN ), Centre National de la Recherche Scientifique ( CNRS ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Laboratoire de Biologie du Développement de Villefranche sur mer ( LBDV ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Institut méditerranéen de biodiversité et d'écologie marine et continentale ( IMBE ), Centre National de la Recherche Scientifique ( CNRS ) -Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université ( AMU ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ), Laboratoire de Biodiversité et Biotechnologies Microbiennes ( LBBM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -PIERRE FABRE-EDF ( EDF ) -Centre National de la Recherche Scientifique ( CNRS ), National University of Ireland [Galway] ( NUI Galway ), Géoazur ( GEOAZUR ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Observatoire de la Côte d'Azur, Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), ~, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-EDF (EDF)-PIERRE FABRE-Université Pierre et Marie Curie - Paris 6 (UPMC)-Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU)
Subjects: 0106 biological sciences, 0301 basic medicine, guanidine alkaloids, 01 natural sciences, Crambe Sponge, Water column, Crambe, Chromatography, High Pressure Liquid, Multidisciplinary, biology, Substrate (biology), natural-products, Flow Cytometry, Chemical ecology, Chemistry, Sea-squirt, Teratogens, Metabolome, ecology, aplysina-fistularis, Metabolo, ics, Crambe crambe, Article, 03 medical and health sciences, Alkaloids, marine-invertebrates, Sponge, Botany, Animals, Metabolomics, Seawater, 14. Life underwater, Urochordata, mediterranean sea, caribbean sponges, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, 010604 marine biology & hydrobiology, Biological Transport, mass-spectrometry, biology.organism_classification, coral-reefs, 030104 developmental biology, Microscopy, Fluorescence, 13. Climate action, Microscopy, Electron, Scanning, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, biologically-active metabolites
Abstract: Ecological interactions in the marine environment are now recognized to be partly held by chemical cues produced by marine organisms. In particular, sponges are sessile animals thought to rely on the bioactive substances they synthesize to ensure their development and defense. However, the mechanisms leading the sponges to use their specialized metabolites as chemical cues remain unknown. Here we report the constant release of bioactive polycyclic guanidinic alkaloids by the Mediterranean sponge Crambe crambe into the dissolved and the particulate phases using a targeted metabolomics study. These compounds were proven to be stored into already described specialized (spherulous) sponge cells and dispersed into the water column after release through the sponge exhaling channels (oscula), leading to a chemical shield surrounding the sponge. Low concentrations of these compounds were demonstrated to have teratogenic effects on embryos of a common sea squirt (ascidian). This mechanism of action called spherulization may therefore contribute to the ecological success of encrusting sponges that need to extend their substrate cover to expand. Part of this work was funded by the region PACA (Plateau MALLABAR), the ECOS Nord project C15U01 by the EMR, a partnership between the UPMC, the Laboratoires Pierre Fabre and CNRS. peer-reviewed
Published: 2016
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37. FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells

Author: Corine Bertolotto, Caroline Bonet, Charlotte Pandiani, Julie Bourseguin, Robert Ballotti, Emilie Renaud, Sandy Giuliano, Filippo Rosselli, Patrycja Pawlikowska, Houda Karmous-Benailly, Marina Boncompagni, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, 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)-Université Côte d'Azur (UCA), Laboratoire de Génétique de la Radiosensibilité (LGR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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), Immunology-Hematology, Centre méditérannéen de médecine moléculaire (C3M), 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), Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, 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: 0301 basic medicine, Indoles, DNA damage, Cell Survival, [SDV]Life Sciences [q-bio], Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, 03 medical and health sciences, Mice, Downregulation and upregulation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, FANCD2, medicine, Gene silencing, Animals, Humans, Gene Silencing, Vemurafenib, Transcription factor, Melanoma, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Microphthalmia-Associated Transcription Factor, Sulfonamides, Multidisciplinary, integumentary system, Fanconi Anemia Complementation Group D2 Protein, Microphthalmia-associated transcription factor, medicine.disease, 3. Good health, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, Reactive Oxygen Species, Oxidation-Reduction, medicine.drug
Abstract: Proteins involved in genetic stability maintenance and safeguarding DNA replication act not only against cancer initiation but could also play a major role in sustaining cancer progression. Here, we report that the FANC pathway is highly expressed in metastatic melanoma harboring the oncogenic microphthalmia-associated transcription factor (MiTF). We show that MiTF downregulation in melanoma cells lowers the expression of several FANC genes and proteins. Moreover, we observe that, similarly to the consequence of MiTF downregulation, FANC pathway silencing alters proliferation, migration and senescence of human melanoma cells. We demonstrate that the FANC pathway acts downstream MiTF and establish the existence of an epistatic relationship between MiTF and the FANC pathway. Our findings point to a central role of the FANC pathway in cellular and chromosomal resistance to both DNA damage and targeted therapies in melanoma cells. Thus, the FANC pathway is a promising new therapeutic target in melanoma treatment.
Published: 2016

38. Deep-UV nitride-on-silicon microdisk lasers

Author: Guillaume Cassabois, Christelle Brimont, Thierry Guillet, Meletios Mexis, Iännis Roland, Y. Zeng, Xavier Checoury, Pierre Valvin, Fabrice Semond, Philippe Boucaud, Bruno Gayral, Julien Selles, Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d'électronique fondamentale (IEF), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Nanophysique et Semiconducteurs (NPSC), PHotonique, ELectronique et Ingénierie QuantiqueS (PHELIQS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 [2016-2019] (UGA [2016-2019])-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), ANR-13-BS10-0010,QUANONIC,Optique quantique et non-linéaire dans des cavités nitrures(2013), ANR-11-LABX-0014,GANEX,Réseau national sur GaN(2011), and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: 010302 applied physics, Multidisciplinary, Materials science, Silicon, business.industry, chemistry.chemical_element, 02 engineering and technology, Substrate (electronics), Nitride, 021001 nanoscience & nanotechnology, 7. Clean energy, 01 natural sciences, Article, Active layer, chemistry, [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], 0103 physical sciences, Sapphire, Optoelectronics, Spontaneous emission, Photonics, 0210 nano-technology, business, Quantum well
Abstract: Deep ultra-violet semiconductor lasers have numerous applications for optical storage and biochemistry. Many strategies based on nitride heterostructures and adapted substrates have been investigated to develop efficient active layers in this spectral range, starting with AlGaN quantum wells on AlN substrates and more recently sapphire and SiC substrates. Here we report an efficient and simple solution relying on binary GaN/AlN quantum wells grown on a thin AlN buffer layer on a silicon substrate. This active region is embedded in microdisk photonic resonators of high quality factors and allows the demonstration of a deep ultra-violet microlaser operating at 275 nm at room temperature under optical pumping, with a spontaneous emission coupling factor β = (4 ± 2) 10−4. The ability of the active layer to be released from the silicon substrate and to be grown on silicon-on-insulator substrates opens the way to future developments of nitride nanophotonic platforms on silicon.
Published: 2016

39. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation

Author: Sébastien Massier, Allison Agus, Margarita Martinez-Medina, Annick Bernalier-Donadille, Jonathan Thévenot, Jérémy Denizot, Elisabeth Billard, Sylvain Denis, Nicolas Barnich, Paul Hofman, Pierre Sauvanet, Richard Bonnet, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Conception, Ingénierie et Développement de l'Aliment et du Médicament (CIDAM), Université d'Auvergne - Clermont-Ferrand I (UdA), Microbiologie Equipe Qualité et Sécurité des Aliments (INRA), Institut National de la Recherche Agronomique (INRA), Microbiologie Environnement Digestif Santé - Clermont Auvergne (MEDIS), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne (UCA), Infection bactérienne, inflammation, et carcinogenèse digestive, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), SECurité des ALIments et Microbiologie, Institut National de la Recherche Agronomique (INRA)-École nationale d'ingénieurs des techniques des industries agricoles et alimentaires (ENITIAA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Unité de Microbiologie (MIC), 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)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), and Inserm UMR1071, INRA (USC), Association F. Aupetit (AFA), Societe Francaise de Nutrition (SFN), ANR 0315443, ANR 'Jeune Chercheuse Jeune Chercheur' Nutribiote, Ministere de la Recherche et de la Technologie
Subjects: Male, 0301 basic medicine, Benzeneacetamides, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Bacterial Adhesion, Receptors, G-Protein-Coupled, Mice, Crohn Disease, Intestinal mucosa, Dietary Sucrose, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Intestinal Mucosa, Receptor, education.field_of_study, Multidisciplinary, Microbiology and Parasitology, Sodium Dodecyl Sulfate, Fecal Microbiota Transplantation, Colitis, Microbiologie et Parasitologie, 3. Good health, régime alimentaire, sucre, matière grasse, Female, Disease Susceptibility, escherichia coli, Agonist, medicine.drug_class, Population, Biology, Diet, High-Fat, Article, 03 medical and health sciences, microbiote, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], inflammation intestinale, medicine, Animals, Humans, education, Feces, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fatty Acids, Volatile, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, Transplantation, 030104 developmental biology, Gene Expression Regulation, Diet, Western, Immunology, Dysbiosis, Gene-Environment Interaction, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Recent advances have shown that the abnormal inflammatory response observed in CD involves an interplay among intestinal microbiota, host genetics and environmental factors. The escalating consumption of fat and sugar in Western countries parallels an increased incidence of CD during the latter 20th century. The impact of a HF/HS diet in mice was evaluated for the gut micro-inflammation, intestinal microbiota composition, function and selection of an E. coli population. The HF/HS diet created a specific inflammatory environment in the gut, correlated with intestinal mucosa dysbiosis characterized by an overgrowth of pro-inflammatory Proteobacteria such as E. coli, a decrease in protective bacteria and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls. Interestingly, mice treated with an agonist of GPR43 were protected against DSS-induced colitis. Finally, the transplantation of feces from HF/HS treated mice to GF mice increased susceptibility to AIEC infection. Together, our results demonstrate that a Western diet could aggravate the inflammatory process and that the activation of the GPR43 receptor pathway could be used as a new strategy to treat CD patients.
Published: 2016

40. Investigating interactions between types of order in categorization

Author: Giulia Mezzadri, Patricia Reynaud-Bouret, Thomas Laloë, Fabien Mathy, Université Côte D'Azur, CNRS, LJAD (France), Bases, Corpus, Langage (UMR 7320 - UCA / CNRS) (BCL), Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), and ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
Subjects: [SCCO]Cognitive science, Rule-based vs. similarity-based orders, Variable vs. constant across-blocks manipulations, Multidisciplinary, Category learning, Category generalization, Interleaved vs. blocked study, Presentation order
Abstract: This study simultaneously manipulates within-category (rule-based vs. similarity-based), between-category (blocked vs. interleaved), and across-blocks (constant vs. variable) orders to investigate how different types of presentation order interact with one another. With regard to within-category orders, stimuli were presented either in a “rule plus exceptions” fashion (in the rule-based order) or by maximizing the similarity between contiguous examples (in the similarity-based order). As for the between-category manipulation, categories were either blocked (in the blocked order) or alternated (in the interleaved order). Finally, the sequence of stimuli was either repeated (in the constant order) or varied (in the variable order) across blocks. This research offers a novel approach through both an individual and concurrent analysis of the studied factors, with the investigation of across-blocks manipulations being unprecedented. We found a significant interaction between within-category and across-blocks orders, as well as between between-category and across-blocks orders. In particular, the combination similarity-based + variable orders was the most detrimental, whereas the combination blocked + constant was the most beneficial. We also found a main effect of across-blocks manipulation, with faster learning in the constant order as compared to the variable one. With regard to the classification of novel stimuli, learners in the rule-based and interleaved orders showed generalization patterns that were more consistent with a specific rule-based strategy, as compared to learners in the similarity-based and blocked orders, respectively. This study shows that different types of order can interact in a subtle fashion and thus should not be considered in isolation.
Published: 2022

41. Shear stress affects the architecture and cohesion of Chlorella vulgaris biofilms

Author: Fanesi, Andrea, Lavayssière, Marc, Breton, Cyril, Bernard, Olivier, Briandet, R, Lopes, Filipa, Laboratoire de Génie des Procédés et Matériaux (LGPM), CentraleSupélec-Université Paris-Saclay, Biological control of artificial ecosystems (BIOCORE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ANR-19-CE43-0002,ALLIGATOR,Coalescence et biofilm dans un photobioréacteur confiné(2019)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV]Life Sciences [q-bio], Science, Plant physiology, biochemical phenomena, metabolism, and nutrition, Article, Confocal microscopy, [SPI]Engineering Sciences [physics], Biofilms, Hydrodynamics, Microalgae, Medicine, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Biomass, Stress, Mechanical, Chlorella vulgaris, Shear Strength
Abstract: International audience; The architecture of microalgae biofilms has been poorly investigated, in particular with respect toshear stress, which is a crucial factor in biofilm-based reactor design and operation. To investigatehow microalgae biofilms respond to different hydrodynamic regimes, the architecture and cohesionof Chlorella vulgaris biofilms were studied in flow-cells at three shear stress: 1.0, 6.5 and 11.0 mPa.Biofilm physical properties and architecture dynamics were monitored using a set of microscopictechniques such as, fluorescence recovery after photobleaching (FRAP) and particle tracking. At lowshear, biofilms cohesion was heterogeneous resulting in a strong basal (close to the substrate) layerand in more loose superficial ones. Higher shear (11.0 mPa) significantly increased the cohesion ofthe biofilms allowing them to grow thicker and to produce more biomass, likely due to a biologicalresponse to resist the shear stress. Interestingly, an acclimation strategy seemed also to occurwhich allowed the biofilms to preserve their growth rate at the different hydrodynamic regimes. Ourresults are in accordance with those previously reported for bacteria biofilms, revealing some generalphysical/mechanical rules that govern microalgae life on substrates. These results may bring newinsights about how to improve productivity and stability of microalgae biofilm-based systems.
Published: 2021

42. ABCC6 deficiency promotes dyslipidemia and atherosclerosis

Author: Daniel Henrion, Janna Zoll, Viola Pomozi, Li-Hsieh Chen, Ludovic Martin, Christopher Brampton, William A. Boisvert, Sheree Kuo, Sara McCurdy, Georges Leftheriotis, Ailea Apana, Simon Blanchard, Olivier Le Saux, Gilles Lambert, University of Hawai'i [Honolulu] (UH), Bio-Rad Laboratories, Partenaires INRAE, University of California [San Diego] (UC San Diego), University of California (UC), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de PhysioMédecine Moléculaire (LP2M), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Bernardo, Elizabeth
Subjects: Male, 0301 basic medicine, 030204 cardiovascular system & hematology, Ectopic calcification, chemistry.chemical_compound, 0302 clinical medicine, Pseudoxanthoma Elasticum, Multidisciplinary, biology, Pseudoxanthoma elasticum, Skin diseases, Experimental models of disease, Medicine, Female, lipids (amino acids, peptides, and proteins), Multidrug Resistance-Associated Proteins, medicine.symptom, medicine.medical_specialty, Science, ABCC6, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammation, Article, Calcification, Bile Acids and Salts, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Animals, Humans, Dyslipidemias, Retrospective Studies, business.industry, Cholesterol, Macrophages, Atherosclerosis, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Peripheral vascular disease, LDL receptor, biology.protein, business, Lipoprotein
Abstract: ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr−/− mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6 and Ldlr genes were fed an atherogenic diet for 16 weeks before intimal calcification, aortic plaque formation and lipoprotein profile were evaluated. Cholesterol efflux and the expression of several inflammation, atherosclerosis and cholesterol homeostasis-related genes were also determined in murine liver and bone marrow-derived macrophages. Furthermore, we examined plasma lipoproteins, vascular calcification, carotid intima-media thickness and atherosclerosis in a cohort of PXE patients with ABCC6 mutations and compared results to dysmetabolic subjects with increased cardiovascular risk. We found that ABCC6 deficiency causes changes in lipoproteins, with decreased HDL cholesterol in both mice and humans, and induces atherosclerosis. However, we found that the absence of ABCC6 does not influence overall vascular mineralization induced with atherosclerosis. Decreased cholesterol efflux from macrophage cells and other molecular changes such as increased pro-inflammation seen in both humans and mice are likely contributors for the phenotype. However, it is likely that other cellular and/or molecular mechanisms are involved. Our study showed a novel physiological role for ABCC6, influencing plasma lipoproteins and atherosclerosis in a haploinsufficient manner, with significant penetrance.
Published: 2021

43. The inhibitory effect of word neighborhood size when reading with central field loss is modulated by word predictability and reading proficiency

Author: Carlos A. Aguilar, Aurélie Calabrèse, Eric Castet, N. Stolowy, Núria Gala, Thomas François, Frédéric Matonti, Lauren Sauvan, Ophtalmologie [Hôpital de la Timone - APMH], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Amaris Research Unit [Biot], Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Paradis Monticelli [Marseille], Laboratoire de psychologie cognitive (LPC), Biologically plausible Integrative mOdels of the Visual system : towards synergIstic Solutions for visually-Impaired people and artificial visiON (BIOVISION), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), ANR-16-CONV-0002,ILCB,ILCB: Institute of Language Communication and the Brain(2016), and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: 0301 basic medicine, Adult, Male, Quality of life, Text simplification, media_common.quotation_subject, Science, Visual impairment, Vision, Low, Article, 03 medical and health sciences, Fluency, 0302 clinical medicine, Reading (process), Human behaviour, medicine, Humans, Attention, media_common, Aged, Aged, 80 and over, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Macular degeneration, Rehabilitation, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, [SCCO.LING]Cognitive science/Linguistics, Middle Aged, Translational research, 030104 developmental biology, Reading, Word recognition, [SCCO.PSYC]Cognitive science/Psychology, 030221 ophthalmology & optometry, Medicine, Trigram, Female, medicine.symptom, Psychology, Sentence, Word (computer architecture), Cognitive psychology
Abstract: International audience; Background: For normally sighted readers, word neighborhood size (i.e., the total number of words that can be formed from a single word by changing only one letter) has a facilitator effect on word recognition. When reading with central field loss (CFL), however, individual letters may not be correctly identified, leading to possible misidentifications and a reverse neighborhood size effect. Here we investigate this inhibitory effect of word neighborhood size on reading performance and whether it is modulated by word predictability and reading proficiency. Methods: Nineteen patients with binocular CFL from 32 to 89 years old (mean ± SD = 75 ± 15) read short sentences presented with the self-paced reading paradigm. Accuracy and reading time were measured for each target word read, along with its predictability, i.e., its probability of occurrence following the two preceding words in the sentence using a trigram analysis. Linear mixed effects models were then fit to estimate the individual contributions of word neighborhood size, predictability, frequency and length on accuracy and reading time, while taking patients’ reading proficiency into account.Results: For the less proficient readers, who have given up daily reading as a consequence of their visual impairment, we found that the effect of neighborhood size was reversed compared to normally sighted readers and of higher amplitude than the effect of frequency. Furthermore, this inhibitory effect is of greater amplitude (up to 50% decrease in reading speed) when a word is not easily predictable because its chances to occur after the two preceding words in a specific sentence are rather low.Conclusion: Severely impaired patients with CFL often quit reading on a daily basis because this task becomes simply too exhausting. Based on our results, we envision lexical text simplification as a new alternative to promote effective rehabilitation in these patients. By increasing reading accessibility for those who struggle the most, text simplification might be used as an efficient rehabilitation tool and daily reading assistive technology, fostering overall reading ability and fluency through increased practice.
Published: 2020

44. Blue to yellow emission from (Ga,In)/GaN quantum wells grown on pixelated silicon substrate

Author: Christophe Largeron, Benjamin Damilano, Marc Portail, Eric Frayssinet, David Cooper, Virginie Brandli, Florian Faure, Daniel Turover, Guy Feuillet, Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: Materials science, Silicon, Color shift, chemistry.chemical_element, lcsh:Medicine, Cathodoluminescence, 02 engineering and technology, Substrate (electronics), Epitaxy, 01 natural sciences, Article, 0103 physical sciences, Lasers, LEDs and light sources, lcsh:Science, Quantum well, 010302 applied physics, [PHYS]Physics [physics], Multidisciplinary, business.industry, lcsh:R, 021001 nanoscience & nanotechnology, Wavelength, chemistry, Semiconductors, Trench, Optoelectronics, lcsh:Q, 0210 nano-technology, business, Materials for optics
Abstract: It is shown that substrate pixelisation before epitaxial growth can significantly impact the emission color of semiconductor heterostructures. The wavelength emission from InxGa1−xN/GaN quantum wells can be shifted from blue to yellow simply by reducing the mesa size from 90 × 90 µm2 to 10 × 10 µm2 of the patterned silicon used as the substrate. This color shift is mainly attributed to an increase of the quantum well thickness when the mesa size decreases. The color is also affected, in a lesser extent, by the trench width between the mesas. Cathodoluminescence hyperspectral imaging is used to map the wavelength emission of the InxGa1−xN/GaN quantum wells. Whatever the mesa size is, the wavelength emission is red-shifted at the mesa edges due to a larger quantum well thickness and In composition.
Published: 2020

45. Transcriptional modulation of AREB-1 by CRISPRa improves plant physiological performance under severe water deficit

Author: de Melo, Bruno Paes, Lourenço-Tessutti, Isabela Tristan, Paixão, Joaquin Felipe Roca, Noriega, Daniel David, Silva, Maria Cristina Mattar, Fontes, Elizabeth Pacheco Batista, Grossi-de-Sa, Maria Fatima, De Melo, Bruno, Lourenço-Tessutti, Isabela, Paixão, Joaquin, Noriega, Daniel, Silva, Maria, de Almeida-Engler, Janice, Fontes, Elizabeth, Grossi-De-Sa, Maria, Brazilian Agricultural Research Corporation (Embrapa), Universidade Federal de Vicosa (UFV), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Universidade Católica de Brasília (UCB), National Institute of Science and Technology (INCT), Institut Sophia Agrobiotech (ISA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), INCT PlantStress Biotech, UCB Pharma SA, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Fundacao de Apoio a Pesquisa do Distrito Federal (FAPDF), Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA), BRUNO PAES DE MELO, UFV, ISABELA TRISTAN LOURENCO TESSUTTI, Cenargen, JOAQUIN FELIPE ROCA PAIXÃO, UFRJ, DANIEL DAVID NORIEGA, UCB, MARIA CRISTINA MATTAR DA SILVA, Cenargen, JANICE DE ALMEIDA-ENGLER, UMR INSTITUT SOPHIA AGROBITECH INRA/CNRS/UNS, FRANCE, ELIZABETH PACHECO BATISTA FONTES, UFV, and MARIA FATIMA GROSSI DE SA, Cenargen.
Subjects: 0106 biological sciences, 0301 basic medicine, Transgene, [SDV]Life Sciences [q-bio], Arabidopsis, lcsh:Medicine, 01 natural sciences, CRISPRa, 03 medical and health sciences, Gene Expression Regulation, Plant, CRISPR-Associated Protein 9, Gene expression, lcsh:Science, AREB-1, Gene, Water deficit, Plant Physiological Phenomena, 2. Zero hunger, Regulation of gene expression, Gene Editing, Multidisciplinary, biology, Dehydration, Arabidopsis Proteins, fungi, lcsh:R, food and beverages, Histone acetyltransferase, Drought tolerance, 15. Life on land, biology.organism_classification, Plants, Genetically Modified, Chromatin, Cell biology, 030104 developmental biology, Basic-Leucine Zipper Transcription Factors, Genetic engineering, [SDE]Environmental Sciences, biology.protein, lcsh:Q, Adaptation, CRISPR-Cas Systems, 010606 plant biology & botany
Abstract: Plants are sessile organisms, which are vulnerable to environmental stresses. As such, plants have developed multiple molecular, physiological, and cellular mechanisms to cope with natural stressors. However, these environmental adversities, including drought, are sources of the main agribusiness problems since they interfere with plant growth and productivity. Particularly under water deprivation conditions, the abscisic acid-responsive element-binding protein AREB1/ABF2 plays an important role in drought stress response and physiological adaptation. In this investigation, we provide substantial confirmation for the role of AREB1/ABF2 in plant survival under severe water deficit using the CRISPR activation (CRISPRa) technique to enhance the AREB1 gene expression. In our strategy, the inactive nuclease dCas9 was fused with an Arabidopsis histone acetyltransferase 1, which improves gene expression by remodeling chromatin. The AREB1 overexpression promotes an improvement in the physiological performance of the transgenic homozygous plants under drought, which was associated with an increase in chlorophyll content, antioxidant enzyme activity, and soluble sugar accumulation, leading to lower reactive oxygen species accumulation. Finally, we found that the CRISPR-mediated up-regulation of AREB1 changes the abundance of several downstream ABA-inducible genes, allowing us to report that CRISPRa dCas9-HAT is a valuable biotechnological tool to improve drought stress tolerance through the positive regulation of AREB1.
Published: 2020

46. Distributed 2D temperature sensing during nanoparticles assisted laser ablation by means of high-scattering fiber sensors

Author: Arman Aitkulov, Aizhan Issatayeva, Zhannat Ashikbayeva, Vassilis J. Inglezakis, Madina Jelbuldina, Paola Saccomandi, Wilfried Blanc, Daniele Tosi, Carlo Molardi, Aidana Beisenova, Nazarbayev University [Kazakhstan], Politecnico di Milano [Milan] (POLIMI), Institut de Physique de Nice (INPHYNI), Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)
Subjects: Materials science, Hot Temperature, Swine, Optical metrology, Nanoparticle, Metal Nanoparticles, lcsh:Medicine, 02 engineering and technology, Biosensing Techniques, Thermometry, 01 natural sciences, Multiplexing, Imaging phantom, Article, law.invention, 010309 optics, Engineering, Microscopy, Electron, Transmission, X-Ray Diffraction, law, 0103 physical sciences, Animals, Fiber, Reflectometry, lcsh:Science, TP155, QC, Multidisciplinary, Laser ablation, Laser diode, Scattering, business.industry, lcsh:R, 021001 nanoscience & nanotechnology, Microscopy, Electron, Scanning, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Optoelectronics, Spectrophotometry, Ultraviolet, [SDV.IB]Life Sciences [q-bio]/Bioengineering, lcsh:Q, Biophotonics, Gold, Laser Therapy, 0210 nano-technology, business
Abstract: The high demand in effective and minimally invasive cancer treatments, namely thermal ablation, leads to the demand for real-time multi-dimensional thermometry to evaluate the treatment effectiveness, which can be also assisted by the use of nanoparticles. We report the results of 20-nm gold and magnetic iron oxide nanoparticles-assisted laser ablation on a porcine liver phantom. The experimental set-up consisting of high-scattering nanoparticle-doped fibers was operated by means of a scattering–level multiplexing arrangement and interrogated via optical backscattered reflectometry, together with a solid-state laser diode operating at 980 nm. The multiplexed 2-dimensional fiber arrangement based on nanoparticle-doped fibers allowed an accurate superficial thermal map detected in real-time.
Published: 2020

47. Activating effective functional hand movements in individuals with complete tetraplegia through neural stimulation

Author: Christine Azevedo Coste, Lucie William, Lucas Fonseca, Arthur Hiairrassary, David Andreu, Antoine Geffrier, Jacques Teissier, Charles Fattal, David Guiraud, Contrôle Artificiel de Mouvements et de Neuroprothèses Intuitives (CAMIN), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), NEURINNOV, Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Clinique Saint-Jean - Sud de France [Montpellier], and Centre Bouffard-Vercelli
Subjects: Upper Extremity, Multidisciplinary, [SDV]Life Sciences [q-bio], Movement, Activities of Daily Living, Humans, Electric Stimulation Therapy, Translational research, Hand, Quadriplegia, Biomedical engineering, Spinal Cord Injuries
Abstract: Individuals with complete cervical spinal cord injury suffer from a permanent paralysis of upper limbs which prevents them from achieving most of the activities of daily living. We developed a neuroprosthetic solution to restore hand motor function. Electrical stimulation of the radial and median nerves by means of two epineural electrodes enabled functional movements of paralyzed hands. We demonstrated in two participants with complete tetraplegia that selective stimulation of nerve fascicles by means of optimized spreading of the current over the active contacts of the multicontact epineural electrodes induced functional and powerful grasping movements which remained stable over the 28 days of implantation. We also showed that participants were able to trigger the activation of movements of their paralyzed limb using an intuitive interface controlled by voluntary actions and that they were able to perform useful functional movements such as holding a can and drinking through a straw.
Published: 2022

48. The individual’s signature of telomere length distribution

Author: Toupance, Simon, Villemonais, Denis, Germain, Daphné, Gégout-Petit, Anne, Albuisson, Eliane, Benetos, Athanase, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Nancyclotep- Experimental Imaging Platform = Plate-forme d'imagerie moléculaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure des Mines de Nancy (ENSMN), Institut Mines-Télécom [Paris] (IMT)-Université de Lorraine (UL), TO Simulate and CAlibrate stochastic models (TOSCA), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, ESPRI-Biobase [CHRU Nancy] (Unité fonctionnelle de la plateforme d’aide à la recherche clinique), This work was supported by the French national program PHRC 2010-A01399-30, the regional project CPER-ITM2P 2015-2020, the French PIA project « Lorraine Université d’Excellence », reference ANR-15-IDEX-04-LUE and the Investments for the Future program under grant agreement No. ANR-15-RHU-0004, IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), Université de Lorraine (UL)-Institut Mines-Télécom [Paris] (IMT), Université de Lorraine (UL), ANR-15-IDEX-04-LUE,LUE,Lorraine Université d'Excellence(2016), and ANR-15-RHU-0004,FIGHT-HF ,Fighting Heart Failure
Subjects: Aged, 80 and over, Male, [STAT.AP]Statistics [stat]/Applications [stat.AP], Telomere length, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, lcsh:R, Telomere Homeostasis, lcsh:Medicine, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, Telomere, Leukocyte telomere length distribution (LTLD), ADELAHYDE study, Article, [STAT]Statistics [stat], Blotting, Southern, LTLD signature, Leukocytes, Linear Models, Humans, Female, lcsh:Q, lcsh:Science, Aged
Abstract: International audience; Mean telomere length in human leukocyte DNA samples reflects the different lengths of telomeres at the ends of the 23 chromosomes and in an admixture of cells. However, only rudimentary information is available regarding the distribution of telomere lengths in all chromosomes and the different cell types in leukocyte samples. Understanding the configuration of leukocyte telomere length distribution (LTLD) could be helpful in capturing intrinsic elements that are not provided by the mean leukocyte telomere length (mLTL). The objective of this study was to analyse LTLD and its temporal variation in adults. Leukocyte samples were donated on two occasions (8 years apart) by 72 participants in the ADELAHYDE study. Telomere length was measured by Southern blotting of the terminal restriction fragments. Individuals with comparable mLTLs displayed different shapes of LTLDs. Inter-individual variation in LTLD shape was much larger than intra-individual variation in LTLD shape between baseline and follow-up leukocyte samples. These results show an important individual stability of LTLD shape over time indicating that each individual has a characteristic LTLD signature.
Published: 2019

49. Type and magnitude of non-compliance and adulteration in neroli, mandarin and bergamot essential oils purchased on-line: potential consumer vulnerability

Author: Marissa Pierson, Xavier Fernandez, Sylvain Antoniotti, Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Nice (ICN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: Natural products, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Science, Medicine, Analytical chemistry, Article, Chemical safety
Abstract: International audience; Abstract Thirty-one samples of essential oils used both in perfumery and aromatherapy were purchased to business-to-consumers suppliers and submitted to standard gas chromatography-based analysis of their chemical composition. Their compliance with ISO AFNOR standards was checked and revealed, although ISO AFNOR ranges are relatively loose, that more than 45% of the samples analyzed failed to pass the test and more than 19% were diluted with solvents such as propylene and dipropylene glycol, triethyl citrate, or vegetal oil. Cases of non-compliance could be due to substitution or dilution with a cheaper essential oil, such as sweet orange oil, blending with selected compounds (linalool and linalyl acetate, maybe of synthetic origin), or issues of aging, harvest, or manufacturing that should be either deliberate or accidental. In some cases, natural variability could be invoked. These products are made available to the market without control and liability by resellers and could expose the public to safety issues, in addition to commercial prejudice, in sharp contrast with the ever-increasing regulations applying to the sector and the high demand of consumers for safe, controlled and traceable products in fragrances and cosmetic products.
Published: 2021

50. Local dispersal pathways during the invasion of the cactus moth, Cactoblastis cactorum, within North America and the Caribbean

Author: Karina Boege, César A. Domínguez, Rubén Pérez-Ishiwara, Guadalupe Andraca-Gómez, Mariano Ordano, Eric Lombaert, Juan Fornoni, Univ Nacl Autonoma Mexico, Institut Sophia Agrobiotech (ISA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), Universidad Nacional de Tucumán (UNT), Universidad Nacional Autónoma de México (UNAM), Comision Nacional para el Uso y Conocimiento de la Biodiversidad CONABIO-JE002, Consejo Nacional de Ciencia y Tecnologia (CONACyT), and Universidad Nacional Autonoma de Mexico
Subjects: 0106 biological sciences, 0301 basic medicine, Population genetics, [SDV]Life Sciences [q-bio], biological invasions, Population Dynamics, lcsh:Medicine, phylogeography, Moths, 01 natural sciences, purl.org/becyt/ford/1 [https], Human Activities, Colonization, hurricane effects, lcsh:Science, Caribbean island, Multidisciplinary, Behavior, Animal, biology, Ecology, Commerce, Opuntia, Caribbean Region, Genetic structure, Cactus, Evolution, 010603 evolutionary biology, Article, 03 medical and health sciences, Plant-animal interactions, Animals, Humans, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Ruderal species, 14. Life underwater, purl.org/becyt/ford/1.6 [https], Genetic diversity, lcsh:R, Bayes Theorem, biology.organism_classification, 030104 developmental biology, North America, Cactoblastis cactorum, Biological dispersal, lcsh:Q, Structural variation, geographical dispersal, Introduced Species, Multiplex Polymerase Chain Reaction, Microsatellite Repeats
Abstract: Cactoblastis cactorum, a species of moth native to Argentina, feeds on several prickly pear cactus species (Opuntia) and has been successfully used as a biological control of invading Opuntia species in Australia, South Africa and native ruderal Opuntia species in some Caribbean islands. Since its introduction to the Caribbean its spread was uncontrolled, invading successfully Florida, Texas and Louisiana. Despite this long history of invasion, we are still far from understanding the factors determining the patterns of invasion of Cactoblastis in North America. Here, we explored three non-mutually exclusive explanations: a) a stepping stone model of colonization, b) long distance colonization due to hurricanes, and/or c) hitchhiking through previously reported commercial routes. Genetic diversity, genetic structure and the patterns of migration among populations were obtained by analyzing 10 nuclear microsatellite loci. Results revealed the presence of genetic structure among populations of C. cactorum in the invaded region and suggest that both marine commercial trade between the Caribbean islands and continental USA, as well as recurrent transport by hurricanes, explain the observed patterns of colonization. Provided that sanitary regulations avoiding humanmediated dispersal are enforced, hurricanes probably represent the most important agent of dispersal and future invasion to continental areas. Fil: Andraca Gómez, Guadalupe. Universidad Nacional Autónoma de México. Instituto de Ecología; México Fil: Lombaert, Eric. Université Côte d'Azur; Francia. Centre National de la Recherche Scientifique; Francia Fil: Ordano, Mariano Andrés. Fundación Miguel Lillo; Argentina. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; Argentina Fil: Pérez Ishiwara, Rubén. Universidad Nacional Autonoma de Mexico. Departamento de Ecología Evolutiva; México Fil: Boege, Karina. Universidad Nacional Autonoma de Mexico. Departamento de Ecología Evolutiva; México Fil: Domínguez, César A.. Universidad Nacional Autonoma de Mexico. Departamento de Ecología Evolutiva; México Fil: Fornoni, Juan. Universidad Nacional Autonoma de Mexico. Departamento de Ecología Evolutiva; México
Published: 2020

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