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1. Dystrophin myonuclear domain restoration governs treatment efficacy in dystrophic muscle

Author: Adrien Morin, Amalia Stantzou, Olga N. Petrova, John Hildyard, Thomas Tensorer, Meriem Matouk, Mina V. Petkova, Isabelle Richard, Tudor Manoliu, Aurélie Goyenvalle, Sestina Falcone, Markus Schuelke, Corinne Laplace-Builhé, Richard J. Piercy, Luis Garcia, Helge Amthor, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Veterinary College [London], University of London [London], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Généthon, Immunologie moléculaire et biothérapies innovantes (IMBI), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Centre Scientifique de Monaco (CSM), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Saclay, Association Française contre les Myopathies, AFM, Agence Nationale de la Recherche, ANR, Deutsch-Französische Hochschule, DFH: CDFA-06-11, We thank Thomas Bestetti, Chloé Dambrune, Karima Relizani, and Cécile Gastaldi for technical assistance. We thank Dr. Feng Zhang for providing the plasmid pX601-AAV-CMV::NLS-SaCas9-NLS-3xHA-bGHpA, and U6::BsaIsgRNA. We also thank Frederic De Leeuw for assistance with multiphoton imaging and Matthieu Dos Santos for preliminary RNA scope experiments. This work was supported by the Association Monegasque contre les Myopathies (AMM, Monaco), the Université Franco-Allemande (CDFA-06-11, UFA), the Association Française contre les Myopathies (AFM, France), and the Agence National de la Recherche (ANR, France).
Subjects: Gene Editing, Multidisciplinary, [SDV]Life Sciences [q-bio], Muscles, dystrophin-EGFP, nuclear domain, Dystrophin, Muscular Dystrophy, Duchenne, Mice, Disease Models, Animal, Treatment Outcome, Mice, Inbred mdx, Animals, Female, mdx mouse, myotendinous junction, Muscle, Skeletal
Abstract: Dystrophin is essential for muscle health: its sarcolemmal absence causes the fatal, X-linked condition, Duchenne muscular dystrophy (DMD). However, its normal, spatial organization remains poorly understood, which hinders the interpretation of efficacy of its therapeutic restoration. Using female reporter mice heterozygous for fluorescently tagged dystrophin ( Dmd EGFP ), we here reveal that dystrophin distribution is unexpectedly compartmentalized, being restricted to myonuclear-defined sarcolemmal territories extending ~80 µm, which we called “basal sarcolemmal dystrophin units (BSDUs).” These territories were further specialized at myotendinous junctions, where both Dmd transcripts and dystrophin protein were enriched. Genome-level correction in X-linked muscular dystrophy mice via CRISPR/Cas9 gene editing restored a mosaic of separated dystrophin domains, whereas transcript-level Dmd correction, following treatment with tricyclo-DNA antisense oligonucleotides, restored dystrophin initially at junctions before extending along the entire fiber—with levels ~2% sufficient to moderate the dystrophic process. We conclude that widespread restoration of fiber dystrophin is likely critical for therapeutic success in DMD, perhaps most importantly, at muscle–tendon junctions.
Published: 2023
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2. Partial Restoration of Brain Dystrophin and Behavioral Deficits by Exon Skipping in the Muscular Dystrophy X-Linked (mdx) Mouse

Author: Faouzi Zarrouki, Karima Relizani, Flavien Bizot, Thomas Tensorer, Luis Garcia, Cyrille Vaillend, Aurélie Goyenvalle, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), SQY Therapeutics, Centre Scientifique de Monaco (CSM), and European Project: 847826,H2020,H2020-SC1-2019-Two-Stage-RTD,BIND(2020)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Oligonucleotides, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Brain, Exons, Oligonucleotides, Antisense, Dystrophin, Muscular Dystrophy, Duchenne, Disease Models, Animal, Mice, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Neurology, Mice, Inbred mdx, Animals, Tissue Distribution, Neurology (clinical)
Abstract: International audience; Objectives: Duchenne muscular dystrophy is associated with various degrees of cognitive impairment and behavioral disturbances. Emotional and memory deficits also constitute reliable outcome measures to assess efficacy of treatments in the mdx mouse lacking the muscle and neuronal full-length dystrophins. The present study aimed to evaluate whether these deficits could be alleviated by the restoration of brain dystrophin.Methods: We performed intracerebroventricular administration of a new potent tricyclo-DNA antisense oligonucleotide (tcDNA-ASO) containing a full phosphodiester backbone conjugated to a palmitic acid moiety (tcDNA-ASO), designed to skip the mutated exon 23 of mdx mice.Results: We first show that the tcDNA-ASO rescues expression of brain dystrophin to 10-30% of wild-type levels and significantly reduces the abnormal unconditioned fear responses in mdx mice in a dose-dependent manner, 5 weeks post-injection. Exon skipping efficiency, ASO biodistribution, protein restoration and effect on the fear response were optimal with a dose of 400 μg at 6-7 weeks post-injection, with synaptic-like expression in brain tissues such as the hippocampus and amygdala. Furthermore, this dose of tcDNA-ASO restored long-term memory retention of mdx mice in an object recognition task, but only had minor effects on fear conditioning.Interpretation: These results suggest for the first time that postnatal re-expression of brain dystrophin could reverse or at least alleviate some cognitive deficits associated with Duchenne muscular dystrophy. ANN NEUROL 2022;92:213-229.
Published: 2022
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3. Positive selection over the mitochondrial genome and its role in the diversification of gentoo penguins in response to adaptation in isolation

Author: Noll, D., Leon, F., Brandt, D., Pistorius, P., Le Bohec, Céline, Bonadonna, F., Trathan P., N., Barbosa, A., Raya Rey, A., Dantas G. P., M., Bowie R. C., K., Poulin, E., Vianna J., A., Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), University of South Carolina [Columbia], DST/NRF Centre of Excellence at the Percy FitzPatrick Institute for African Ornithology [South Africa], Nelson Mandela Metropolitan University [Port Elizabeth, South Africa], Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Ecologie comportementale (EC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Universidad de Chile = University of Chile [Santiago] (UCHILE), Pontificia Universidad Católica de Chile (UC), University of California [Berkeley], University of California, Nelson Mandela University [Port Elizabeth], Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), British Antarctic Survey (BAS), Natural Environment Research Council (NERC), Museo Nacional de Ciencias Naturales [Madrid] (MNCN), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad Nacional de Tierra del Fuego, Antártida e islas del Atlántico Sur (UNTDF), Centro Austral de Investigaciones Científicas [Ushuaia] (CADIC), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Pontifícia Universidade Católica de Minas Gerais (PUC Minas), University of California [Berkeley] (UC Berkeley), University of California (UC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE)
Subjects: [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Phylogeography, Multidisciplinary, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV]Life Sciences [q-bio], Genome, Mitochondrial, Animals, Antarctic Regions, DNA, Mitochondrial, Spheniscidae, Phylogeny
Abstract: Although mitochondrial DNA has been widely used in phylogeography, evidence has emerged that factors such as climate, food availability, and environmental pressures that produce high levels of stress can exert a strong influence on mitochondrial genomes, to the point of promoting the persistence of certain genotypes in order to compensate for the metabolic requirements of the local environment. As recently discovered, the gentoo penguins (Pygoscelis papua) comprise four highly divergent lineages across their distribution spanning the Antarctic and sub-Antarctic regions. Gentoo penguins therefore represent a suitable animal model to study adaptive processes across divergent environments. Based on 62 mitogenomes that we obtained from nine locations spanning all four gentoo penguin lineages, we demonstrated lineage-specific nucleotide substitutions for various genes, but only lineage-specific amino acid replacements for the ND1 and ND5 protein-coding genes. Purifying selection (dN/dS 1) was mostly present in codons of the Complex I (NADH genes), supported by two different codon-based methods at the ND1 and ND4 in the most divergent lineages, the eastern gentoo penguin from Crozet and Marion Islands and the southern gentoo penguin from Antarctica respectively. Additionally, ND5 and ATP6 were under selection in the branches of the phylogeny involving all gentoo penguins except the eastern lineage. Our study suggests that local adaptation of gentoo penguins has emerged as a response to environmental variability promoting the fixation of mitochondrial haplotypes in a non-random manner. Mitogenome adaptation is thus likely to have been associated with gentoo penguin diversification across the Southern Ocean and to have promoted their survival in extreme environments such as Antarctica. Such selective processes on the mitochondrial genome may also be responsible for the discordance detected between nuclear- and mitochondrial-based phylogenies of gentoo penguin lineages., Financial support for this study was provided by Beca ANID Doctorado Nacional (Folio: 21171214), Millennium Institute Biodiversity of Antarctic and Subantarctic Ecosystems (BASE) ANID—Millennium Science Initiative Program—ICN2021_002, Inach RT_12-14, Fondecyt 1150517, PIA ACT172065 GAB, Center of genome regulation (CRG) ANID/FONDAP/15200002, the CNPq (431463/2016-6) and the PROANTAR, IPEV programs 137 ANTAVIA-ECOPHY and 354 ETHOTAAF and by the Spanish Research Agency (CGL2004-01348, CGL2007-60369, POL2006-06635 and CTM2015-64720-R).
Published: 2022
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4. The Effect of Thermal Stress on the Physiology and Bacterial Communities of Two Key Mediterranean Gorgonians

Author: Romie Tignat-Perrier, Jeroen A. J. M. van de Water, Dorian Guillemain, Didier Aurelle, Denis Allemand, Christine Ferrier-Pagès, Centre Scientifique de Monaco (CSM), Institut Pythéas (OSU PYTHEAS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Institut méditerranéen d'océanologie (MIO), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ecology, Bacteria, [SDV]Life Sciences [q-bio], Microbiota, Mediterranean Sea, Animals, Seawater, Anthozoa, Applied Microbiology and Biotechnology, Food Science, Biotechnology
Abstract: In the Mediterranean Sea, the tree-shaped gorgonian corals form large forests that provide a place to live for many species. Because of this important ecological role, it is crucial to understand how common habitat-forming gorgonians, like Eunicella cavolini and Paramuricea clavata , are affected by high seawater temperatures that are expected in the future due to climate change.
Published: 2022
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5. Cancer-associated fibroblasts in renal cell carcinoma: implication in prognosis and resistance to anti-angiogenic therapy

Author: Christopher Montemagno, Gilles Pagès, Renaud Grépin, Arnaud Borderie, Michael Coutts, Delphine Borchiellini, Damien Ambrosetti, Charlotte Paoli, Matthieu Durand, Jean-Christophe Bernhard, Nathalie Rioux-Leclercq, Olivia Rastoin, Maeva Dufies, 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), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Laboratoire International Associé Réponse des Organismes et Populations face au Stress Environnemental - Université Côte d’Azur - Centre Scientifique de Monaco (LIA ROPSE), Université Côte d’Azur - Centre Scientifique de Monaco, Centre Scientifique de Monaco (CSM), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), CHU Bordeaux [Bordeaux], Fondation de France, Ligue Nationale contre le Cancer (Equipe Labellisee 2019), French National Institute for Cancer Research (INCA), Cordon de vie Foundation, l'Institut National du Cancer (INCa) Institut National du Cancer (INCA) France, Government of the Principality of Monaco, FX Mora Foundation, Université Nice Sophia Antipolis (... - 2019) (UNS), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Fondation de FranceFondation de France, and l'Institut National du Cancer (INCa)Institut National du Cancer (INCA) France
Subjects: Male, #uroonc, anti-angiogenic treatment, [SDV]Life Sciences [q-bio], Angiogenesis Inhibitors, clear cell renal cell carcinoma, Nephrectomy, Metastasis, chemistry.chemical_compound, Mice, 0302 clinical medicine, Renal cell carcinoma, Cell Movement, Sunitinib, Medicine, Cytotoxic T cell, Lymphangiogenesis, Aged, 80 and over, 0303 health sciences, Neovascularization, Pathologic, Cell migration, Cell Differentiation, Middle Aged, Kidney Neoplasms, Neoadjuvant Therapy, 3. Good health, Vascular endothelial growth factor, Survival Rate, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Female, cancer-associated fibroblasts, Adult, Urology, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, resistance, 03 medical and health sciences, Cell Line, Tumor, Endopeptidases, Biomarkers, Tumor, Animals, Humans, Carcinoma, Renal Cell, 030304 developmental biology, Aged, Retrospective Studies, #kcsm, business.industry, Membrane Proteins, medicine.disease, Actins, Capillaries, Clear cell renal cell carcinoma, chemistry, Drug Resistance, Neoplasm, fibroblast-associated protein, #KidneyCancer, Cancer research, Cancer-Associated Fibroblasts, business, Transcriptome, prognostic marker
Abstract: International audience; Objectives: To investigate the role of cancer-associated fibroblasts (CAFs) in clear cell renal cell carcinoma (ccRCC) with respect to tumour aggressiveness, metastasis development, and resistance to anti-angiogenic therapy (vascular endothelial growth factor receptor-tyrosine kinase inhibitors [VEGFR-TKI]).Patients and methods: Our study involved tissue samples from three distinct and independent cohorts of patients with ccRCC. The presence of CAFs and tumour lymphangiogenesis was investigated, respectively, by transcriptional signatures and then correlated with tumour development and prognosis. The effect of these CAFs on tumour cell migration and VEGFR-TKI resistance was analysed on co-cultures of ccRCC cells with CAFs.Results: Results from our cohorts and from in silico investigations showed that VEGFR-TKI significantly increase the number of CAFs in tumours. In the same populations of patients with ccRCC, the proportion of intra-tumoral CAFs correlated to shorter disease-free and overall survival. The presence of CAFs was also correlated with lymphangiogenesis and lymph node metastasis. CAFs increased the migration and decreased the VEGFR-TKI-dependent cytotoxic effect of tumour cells.Conclusions: Our results show that VEGFR-TKI promote the development of CAFs, and CAFs favour tumour aggressiveness, metastatic dissemination, and resistance to treatment in ccRCC. CAFs could represent a new therapeutic target to fight resistance to treatment of ccRCC. Targeting CAF and immunotherapies combination are emerging as efficient treatments in many types of solid tumours. Our results highlight their relevance in ccRCC.
Published: 2022
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6. Targeting of the ELR+CXCL/CXCR1/2 Pathway Is a Relevant Strategy for the Treatment of Paediatric Medulloblastomas

Author: Manon Penco-Campillo, Clément Molina, Patricia Piris, Nouha Soufi, Manon Carré, Marina Pagnuzzi-Boncompagni, Vincent Picco, Maeva Dufies, Cyril Ronco, Rachid Benhida, Sonia Martial, Gilles Pagès, MARTIAL, Sonia, 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), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Scientifique de Monaco (CSM), Institut de Chimie de Nice (ICN), 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: paediatric medulloblastoma, [SDV]Life Sciences [q-bio], General Medicine, targeted therapy, Receptors, Interleukin-8A, [SDV] Life Sciences [q-bio], Mice, angiogenesis, CXCR1/2, ELR+CXCL cytokines, Quality of Life, Animals, Neoplasm Recurrence, Local, Cerebellar Neoplasms, Medulloblastoma
Abstract: International audience; Medulloblastoma (MB) is the most common and aggressive paediatric brain tumour. Although the cure rate can be as high as 70%, current treatments (surgery, radio- and chemotherapy) excessively affect the patients’ quality of life. Relapses cannot be controlled by conventional or targeted treatments and are usually fatal. The strong heterogeneity of the disease (four subgroups and several subtypes) is related to innate or acquired resistance to reference treatments. Therefore, more efficient and less-toxic therapies are needed. Here, we demonstrated the efficacy of a novel inhibitor (C29) of CXCR1/2 receptors for ELR+CXCL cytokines for the treatment of childhood MB. The correlation between ELR+CXCL/CXCR1/2 expression and patient survival was determined using the R2: Genomics Analysis and Visualization platform. In vitro efficacy of C29 was evaluated by its ability to inhibit proliferation, migration, invasion, and pseudo-vessel formation of MB cell lines sensitive or resistant to radiotherapy. The growth of experimental MB obtained by MB spheroids on organotypic mouse cerebellar slices was also assayed. ELR+CXCL/CXCR1/2 levels correlated with shorter survival. C29 inhibited proliferation, clone formation, CXCL8/CXCR1/2-dependent migration, invasion, and pseudo-vessel formation by sensitive and radioresistant MB cells. C29 reduced experimental growth of MB in the ex vivo organotypic mouse model and crossed the blood–brain barrier. Targeting CXCR1/2 represents a promising therapeutic strategy for the treatment of paediatric MB in first-line treatment or after relapse following conventional therapy.
Published: 2022
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7. Experimental and computational modeling for signature and biomarker discovery of renal cell carcinoma progression

Author: Cooley, Lindsay, Rudewicz, Justine, Souleyreau, Wilfried, Emanuelli, Andrea, Alvarez-Arenas, Arturo, Clarke, Kim, Falciani, Francesco, Dufies, Maeva, Lambrechts, Diether, Modave, Elodie, Chalopin-Fillot, Domitille, Pineau, Raphael, Ambrosetti, Damien, Bernhard, Jean-Christophe, Ravaud, Alain, Négrier, Sylvie, Ferrero, Jean-Marc, Pagès, Gilles, Benzekry, Sebastien, Nikolski, Macha, Bikfalvi, Andreas, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), 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)-Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation Mathématique pour l'Oncologie (MONC), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Mathematical Oncology Laboratory [Ciudad Real] (MôLAB), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), University of Liverpool, Centre Scientifique de Monaco (CSM), 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), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Hôpital Pasteur [Nice] (CHU), service d'urologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: EXPRESSION, Biochemistry & Molecular Biology, PROGNOSIS, Tumor model, INHIBITION, Prognostic markers renal cell carcinoma, SUNITINIB, Models, Biological, VALIDATION, Metastasis, SAA2, Mice, Cell Line, Tumor, Biomarkers, Tumor, Animals, Humans, R PACKAGE, Carcinoma, Renal Cell, RC254-282, Science & Technology, Gene Expression Profiling, Research, Computational model, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Computational Biology, Disease Management, SERUM AMYLOID ALPHA, Genomics, Prognosis, CANCER, Systems biology approach, Kidney Neoplasms, Disease Models, Animal, Gene Ontology, CFB, Oncology, SURVIVAL, Heterografts, Disease Susceptibility, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Life Sciences & Biomedicine
Abstract: Background Renal Cell Carcinoma (RCC) is difficult to treat with 5-year survival rate of 10% in metastatic patients. Main reasons of therapy failure are lack of validated biomarkers and scarce knowledge of the biological processes occurring during RCC progression. Thus, the investigation of mechanisms regulating RCC progression is fundamental to improve RCC therapy. Methods In order to identify molecular markers and gene processes involved in the steps of RCC progression, we generated several cell lines of higher aggressiveness by serially passaging mouse renal cancer RENCA cells in mice and, concomitantly, performed functional genomics analysis of the cells. Multiple cell lines depicting the major steps of tumor progression (including primary tumor growth, survival in the blood circulation and metastatic spread) were generated and analyzed by large-scale transcriptome, genome and methylome analyses. Furthermore, we performed clinical correlations of our datasets. Finally we conducted a computational analysis for predicting the time to relapse based on our molecular data. Results Through in vivo passaging, RENCA cells showed increased aggressiveness by reducing mice survival, enhancing primary tumor growth and lung metastases formation. In addition, transcriptome and methylome analyses showed distinct clustering of the cell lines without genomic variation. Distinct signatures of tumor aggressiveness were revealed and validated in different patient cohorts. In particular, we identified SAA2 and CFB as soluble prognostic and predictive biomarkers of the therapeutic response. Machine learning and mathematical modeling confirmed the importance of CFB and SAA2 together, which had the highest impact on distant metastasis-free survival. From these data sets, a computational model predicting tumor progression and relapse was developed and validated. These results are of great translational significance. Conclusion A combination of experimental and mathematical modeling was able to generate meaningful data for the prediction of the clinical evolution of RCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01416-5.
Published: 2021
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8. Low levels of ultra-violet radiation mitigate the deleterious effects of nitrate and thermal stress on coral photosynthesis

Author: Alice C.A. Blanckaert, Laura Fernandes de Barros Marangoni, Renaud Grover, Christine Ferrier-Pagès, Cécile Rottier, Centre Scientifique de Monaco (CSM), Sorbonne Université - Institut de Formation Doctorale (IFD ), and Sorbonne Université (SU)
Subjects: 0106 biological sciences, Coral, Ultra-violet, 010501 environmental sciences, Oceanography, Nitrate, 01 natural sciences, chemistry.chemical_compound, MESH: Animals, MESH: Ecosystem, Photosynthesis, MESH: Photosynthesis, Abiotic component, geography.geographical_feature_category, MESH: Symbiosis, biology, Coral Reefs, Eutrophication, Anthozoa, Pollution, MESH: Nitrates, Environmental chemistry, [SDE]Environmental Sciences, population characteristics, MESH: Coral Reefs, geographic locations, Coral bleaching, Ultraviolet Rays, Pocillopora damicornis, Aquatic Science, Animals, Ecosystem, 14. Life underwater, Symbiosis, Reef, 0105 earth and related environmental sciences, geography, Nitrates, 010604 marine biology & hydrobiology, fungi, technology, industry, and agriculture, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, chemistry, 13. Climate action, MESH: Anthozoa, MESH: Ultraviolet Rays
Abstract: International audience; Reef ecosystems are under increasing pressure from global and local stressors. Rising seawater temperature and high ultraviolet radiation (UVR) levels are the main drivers of the disruption of the coral-dinoflagellate symbiosis (bleaching). Bleaching can also be exacerbated by nitrate contamination in coastal reefs. However, the underlying physiological mechanisms are still poorly understood. Here, we assessed the physiological and oxidative state of the scleractinian coral Pocillopora damicornis, maintained eight weeks in a crossed-factorial design including two temperatures (26 °C or 30 °C), and two nitrate (0.5 and 3 μM-enriched), and UVR (no UVR and 25/1.5 Wm−2 UVA/B) levels. Nitrate enrichment, and high temperature, significantly impaired coral photosynthesis. However, UVR alleviated the nitrate and temperature-induced decrease in photosynthesis, by increasing the coral's antioxidant capacity. The present study contributes to our understanding of the combined effects of abiotic stressors on coral bleaching susceptibility. Such information is urgently needed to refine reef management strategies.
Published: 2021
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9. Noise pollution on coral reefs? — A yet underestimated threat to coral reef communities

Author: Frédéric Bertucci, David Lecchini, Miguel C. Leal, Dominik W. Schmid, Christine Ferrier-Pagès, Ricardo Calado, Denis Allemand, Centre Scientifique de Monaco (CSM), Centro de Estudos do Ambiante e do Mar (CESAM), Universidade de Aveiro, Université de Liège, Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence CORAIL (LabEX CORAIL), Université des Antilles (UA)-Institut d'écologie et environnement-Université de la Nouvelle-Calédonie (UNC)-Université de la Polynésie Française (UPF)-Université de La Réunion (UR)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Université des Antilles et de la Guyane (UAG)-Institut de Recherche pour le Développement (IRD)
Subjects: 0106 biological sciences, Coral, Artisanal fishing, 010501 environmental sciences, Aquatic Science, Oceanography, 01 natural sciences, Environmental monitoring, Animals, 14. Life underwater, Reef, Recreation, Ecosystem, Ships, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, geography, geography.geographical_feature_category, Noise pollution, Coral Reefs, 010604 marine biology & hydrobiology, Fishes, Coral reef, Anthozoa, Pollution, Fishery, Noise, Sound, 13. Climate action, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: Noise pollution is an anthropogenic stressor that is increasingly recognized for its negative impact on the physiology, behavior and fitness of marine organisms. Driven by the recent expansion of maritime shipping, artisanal fishing and tourism (e.g., motorboats used for recreational purpose), underwater noise increased greatly on coral reefs. In this review, we first provide an overview on how reef organisms sense and use sound. Thereafter we review the current knowledge on how underwater noise affects different reef organisms. Although the majority of available examples are limited to few fish species, we emphasize how the impact of noise differs based on an organisms' acoustic sensitivity, mobility and developmental stage, as well as between noise type, source and duration. Finally, we highlight measures available to governments, the shipping industry and individual users and provide directions for polices and research aimed to manage this global issue of noise emission on coral reefs.
Published: 2021
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10. Escherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice

Author: Alexandre Gallerand, Arnaud Jacquel, Pedro Henrique Viana Saavedra, Cedric Torre, Paul Chaintreuil, Sandrine Marchetti, Alissa Majoor, Mohamed Lamkanfi, Raymond Ruimy, Céline Loubatier, Amaury Rey, Anne Doye, Laurent Boyer, Benedicte F. Py, Grégory Michel, Johan Courjon, Rodolphe Guinamard, Patrick Munro, Dorota Czerucka, Orane Visvikis, Océane Dufies, Els Verhoeyen, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Laboratoire International Associé Réponse des Organismes et Populations face au Stress Environnemental - Université Côte d’Azur - Centre Scientifique de Monaco (LIA ROPSE), Université Côte d’Azur - Centre Scientifique de Monaco, Université Nice Sophia Antipolis (1965 - 2019) (UNS), Universiteit Gent = Ghent University (UGENT), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE15-0001,AVI,Identification de l'inflammasome impliqué dans l'Immunité Anti-Virulence: Impact sur notre façon de combattre la bactériémie(2017), École normale supérieure - Lyon (ENS 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), and Guinamard, Rodolphe
Subjects: Microbiology (medical), Inflammasomes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Bacterial Toxins, Bacteremia, GTPase, Applied Microbiology and Biotechnology, Microbiology, Article, 03 medical and health sciences, Mice, PAK1, NLR Family, Pyrin Domain-Containing 3 Protein, Genetics, medicine, Escherichia coli, Animals, Phosphorylation, p21-activated kinases, Escherichia coli Infections, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, integumentary system, 030306 microbiology, Chemistry, Kinase, Escherichia coli Proteins, Pyroptosis, Pattern recognition receptor, Inflammasome, Cell Biology, Bacterial Load, Immunity, Innate, 3. Good health, Cell biology, rac GTP-Binding Proteins, [SDV] Life Sciences [q-bio], Cytokine, p21-Activated Kinases, medicine.drug, Signal Transduction
Abstract: Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition receptor that is also known as cryopyrin, triggers the assembly of the inflammasome-activating caspase-1 through the recruitment of ASC and Nek7. The activation of the NLRP3 inflammasome is tightly controlled both transcriptionally and post-translationally. Despite the importance of the NLRP3 inflammasome regulation in autoinflammatory and infectious diseases, little is known about the mechanism controlling the activation of NLRP3 and the upstream signalling that regulates the NLRP3 inflammasome assembly. We have previously shown that the Rho-GTPase-activating toxin from Escherichia coli cytotoxic necrotizing factor-1 (CNF1) activates caspase-1, but the upstream mechanism is unclear. Here, we provide evidence of the role of the NLRP3 inflammasome in sensing the activity of bacterial toxins and virulence factors that activate host Rho GTPases. We demonstrate that this activation relies on the monitoring of the toxin’s activity on the Rho GTPase Rac2. We also show that the NLRP3 inflammasome is activated by a signalling cascade that involves the p21-activated kinases 1 and 2 (Pak1/2) and the Pak1-mediated phosphorylation of Thr 659 of NLRP3, which is necessary for the NLRP3–Nek7 interaction, inflammasome activation and IL-1β cytokine maturation. Furthermore, inhibition of the Pak–NLRP3 axis decreases the bacterial clearance of CNF1-expressing UTI89 E. coli during bacteraemia in mice. Taken together, our results establish that Pak1 and Pak2 are critical regulators of the NLRP3 inflammasome and reveal the role of the Pak–NLRP3 signalling axis in vivo during bacteraemia in mice. Here, the authors present the upstream pathway that controls the activation of the NLRP3 inflammasome during bacteraemia. The CNF1 toxin from Escherichia coli activates the Rho GTPase Rac2 and its activity is sensed by NLRP3, which is activated by a signalling cascade involving p21-activated kinases 1 and 2.
Published: 2021
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11. VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells

Author: Amandine Morot, Audrey Claren, Jérôme Doyen, Fanny Burel-Vandenbos, Steven C. Clifford, Manon Penco-Campillo, Rita Hanna, Matthew Selby, Bastien Mejias, Jérôme Durivault, Álvaro Javier Feliz Morel, Gilles Pagès, Sonia Martial, Magalie Leloire, Daniel Williamson, Marina Pagnuzzi, Yannick Comoglio, Vincent Picco, 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), Service d'anatomo-pathologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Wolfson Childhood Cancer Research Centre, Newcastle University [Newcastle], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), and UNICANCER-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Epithelial-Mesenchymal Transition, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Cell, Vascular Endothelial Growth Factor C, Medicine (miscellaneous), Biology, General Biochemistry, Genetics and Molecular Biology, Article, Paediatric cancer, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Line, Tumor, medicine, Lymphatic vessel, Biomarkers, Tumor, Animals, Humans, Receptor, Author Correction, lcsh:QH301-705.5, Cell Proliferation, Medulloblastoma, Neovascularization, Pathologic, Cell growth, Growth factor, medicine.disease, Prognosis, In vitro, 3. Good health, Gene Expression Regulation, Neoplastic, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Vascular endothelial growth factor C, lcsh:Biology (General), 030220 oncology & carcinogenesis, Cancer research, Disease Progression, Heterografts, Lymph Nodes, General Agricultural and Biological Sciences, Tumour angiogenesis
Abstract: Medulloblastoma (MB), the most common brain pediatric tumor, is a pathology composed of four molecular subgroups. Despite a multimodal treatment, 30% of the patients eventually relapse, with the fatal appearance of metastases within 5 years. The major actors of metastatic dissemination are the lymphatic vessel growth factor, VEGFC, and its receptors/co-receptors. Here, we show that VEGFC is inversely correlated to cell aggressiveness. Indeed, VEGFC decreases MB cell proliferation and migration, and their ability to form pseudo-vessel in vitro. Irradiation resistant-cells, which present high levels of VEGFC, lose the ability to migrate and to form vessel-like structures. Thus, irradiation reduces MB cell aggressiveness via a VEGFC-dependent process. Cells intrinsically or ectopically overexpressing VEGFC and irradiation-resistant cells form smaller experimental tumors in nude mice. Opposite to the common dogma, our results give strong arguments in favor of VEGFC as a negative regulator of MB growth., Manon Penco-Campillo, Yannick Comoglio et al. show that VEGFC decreases the proliferation and migration of medulloblastoma cells, as well as their ability to form pseudo vessels. Cells expressing high levels of VEGFC also form smaller tumors when subcutaneously injected into the flank of nude mice, thus highlighting a negative regulatory role for VEGFC on tumor growth.
Published: 2020
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12. Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma

Author: Emmanuel Chamorey, Wilfried Souleyreau, Alain Ravaud, Xingkang He, Papa Diogop Ndiaye, Lindsay S. Cooley, Sandy Giuliano, Nathalie M. Mazure, Benoit Beuselinck, Jessica Zucman-Rossi, Damien Ambrosetti, Patrick Auberger, Anais Hagege, Nathalie Rioux-Leclercq, Renaud Schiappa, Julien Parola, Karim Bensalah, Delphine Borchiellini, Stéphanie Torrino, Gilles Pagès, Andreas Bikfalvi, Yihai Cao, Nicolas Nottet, Baharia Mograbi, Jean-Christophe Bernhard, Annelies Verbiest, Maeva Dufies, mazure, nathalie, Centre Scientifique de Monaco (CSM), Laboratoire International Associé Réponse des Organismes et Populations face au Stress Environnemental - Université Côte d’Azur - Centre Scientifique de Monaco (LIA ROPSE), Université Côte d’Azur - Centre Scientifique de Monaco, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Karolinska Institutet [Stockholm], Centre méditerranéen 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)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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 de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), 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), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: 0301 basic medicine, Life Sciences & Biomedicine - Other Topics, Embryo, Nonmammalian, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Cell Cycle Proteins, Drug resistance, Metastasis, Cohort Studies, Tumour biomarkers, Mice, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Biology (General), Neoplasm Metastasis, Zebrafish, Sunitinib, Kinase, Kidney Neoplasms, 3. Good health, Up-Regulation, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, Gene Expression Regulation, Neoplastic, Cancer therapeutic resistance, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Female, General Agricultural and Biological Sciences, Life Sciences & Biomedicine, medicine.drug, QH301-705.5, Mice, Nude, Protein Serine-Threonine Kinases, PLK1, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Targeted therapies, Downregulation and upregulation, In vivo, Cell Line, Tumor, Proto-Oncogene Proteins, medicine, Animals, Humans, Biology, Carcinoma, Renal Cell, Cell Proliferation, Science & Technology, business.industry, medicine.disease, Clear cell renal cell carcinoma, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, business, Tumour angiogenesis
Abstract: Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients., Dufies et al. find high Plk1 expression levels in aggressive clear cell renal cell carcinoma and discover that Plk1 is transcriptionally upregulated in a manner dependent on HIF-2. They also find that high Plk1 expression is correlated to a poor prognosis and resistance to tyrosine kinase inhibitor against VEGF receptor, suggesting a critical role for hypoxia/HIF-2-induced Plk1 in disease progression.
Published: 2020
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13. Insect decline: immediate action is needed

Author: Louis Lambrechts, Anna-Bella Failloux, Yvon Le Maho, Hervé Jactel, Jean-Dominique Lebreton, Philippe Grandcolas, Pascale Cossart, Jean-Luc Imler, Jean-Claude Duplessy, Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Modèles Insectes de l'Immunité Innée (M3I), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris], Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-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), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Paléocéanographie (PALEOCEAN), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier 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), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE)
Subjects: 0106 biological sciences, 0301 basic medicine, Insecta, Pollination, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Population, Biodiversity, Insect, Conservation, Biology, Extinction, Biological, 01 natural sciences, 03 medical and health sciences, Decline, Animals, Humans, Ecosystem, education, Global change, media_common, 2. Zero hunger, education.field_of_study, Agroforestry, business.industry, fungi, Agriculture, General Medicine, 15. Life on land, Pesticide, 030104 developmental biology, Habitat, 13. Climate action, [SDE]Environmental Sciences, business, 010606 plant biology & botany
Abstract: Insects appeared more than 400 million years ago and they represent the richest and most diverse taxonomic group with several million species. Yet, under the combined effect of the loss of natural habitats, the intensification of agriculture with massive use of pesticides, global warming and biological invasions, insects show alarming signs of decline. Although difficult to quantify, species extinction and population reductions are confirmed for many ecosystems. This results in a loss of services such as the pollination of plants, including food crops, the recycling of organic matter, the supply of goods such as honey and the stability of food webs. It is therefore urgent to halt the decline of Insects. We recommend implementing long-term monitoring of populations, tackling the causes of insect decline by reducing the use of synthetic insecticides, preserving natural habitats, and reinventing a positive relationship between humans and insects.Apparus il y a plus de 400 millions d’années, les Insectes représentent le groupe taxonomique le plus riche et diversifié, avec plusieurs millions d’espèces. Sous l’effet de la disparition des habitats, de l’intensification de l’agriculture avec l’usage massif des pesticides, du réchauffement climatique et des invasions biologiques, les Insectes montrent des signes alarmants de déclin. Bien que difficiles à quantifier, la disparition des espèces et la réduction de leurs populations sont avérées et communes à de nombreux écosystèmes. Elles se traduisent par une perte des services rendus, comme la pollinisation des plantes vivrières, le recyclage de la matière organique, la fourniture de biens comme le miel, et l’équilibre des réseaux trophiques. Il est donc urgent de freiner le déclin des Insectes. Pour cela, il faut mettre en œuvre des suivis à long terme des populations, réduire l’usage des insecticides de synthèse, préserver les habitats naturels, et réinventer la relation de l’Homme à l’Insecte en revalorisant son image et ses usages.
Published: 2020
Full Text: View/download PDF

14. The Tara Pacific expedition-A pan-ecosystemic approach of the '-omics' complexity of coral reef holobionts across the Pacific Ocean

Author: Planes, Serge, Allemand, Denis, Agostini, Sylvain, Banaigs, Bernard, Boissin, Emilie, Boss, Emmanuel, Bourdin, Guillaume, Bowler, Chris, Douville, Eric, Flores, J. Michel, Forcioli, Didier, Furla, Paola, Galand, Pierre E., Ghiglione, Jean-francois, Gilson, Eric, Lombard, Fabien, Moulin, Clementine, Pesant, Stephane, Poulain, Julie, Reynaud, Stephanie, Romac, Sarah, Sullivan, Matthew B., Sunagawa, Shinichi, Thomas, Olivier P., Trouble, Romain, De Vargas, Colomban, Thurber, Rebecca Vega, Voolstra, Christian R., Wincker, Patrick, Zoccola, Didier, Planes, S., Allemand, D., Agostini, S., Armstrong, E., Audrain, S., Aury, J-m, Banaig, B., Barbe, V, Belser, C., Beraud, E., Boissin, E., Bonnival, E., Boss, E., Bourdin, G., Bourgois, E., Bowler, C., Carradec, Q., Cassar, N., Cohen, N. R., Conan, P., Cronin, D. R., Da Silva, O., De Vargas, C., Djerbi, N., Dolan, J. R., Herta, Dominguez G., Du J, Filee, J., Flores, J. M., Forcioli, D., Friedrich, R., Furla, P., Galand, P. E., Ghiglione, J-f, Gilson, E., Gorsky, G., Guinther, M., Haentjens, N., Henry, N., Hertau, M., Hochart, C., Hume, B. C. C., Iwankow, G., John, S. G., Karp-boss, L., Kelly, R. L., Kitano, Y., Klinges, G., Koren, I, Labadie, K., Lancelot, J., Lang-yona, N., Le-hoang, J., Lemee, R., Lin, Y., Lombard, F., Marie, D., Mcmind, R., Miguel-gordo, M., Trainic, M., Monmarche, D., Moulin, C., Mucherie, Y., Noel, B., Ottaviani, A., Paoli, L., Pedrotti, M-l, Pesant, S., Pogoreutz, C., Poulain, J., Pujo-pay, M., Reverdin, G., Reynaud, S., Romac, S., Rothig, T., Rottinger, E., Rouan, A., Ruscheweyh, H-j, Salazar, G., Sullivan, M. B., Sunagawa, S., Thomas, O. P., Trouble, R., Vardi, A., Vega-thunder, R., Voolstra, C. R., Wincker, P., Zahed, A., Zamoum, T., Ziegler, M., Zoccola, D., Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence CORAIL (LabEX CORAIL), Institut de Recherche pour le Développement (IRD)-Université des Antilles et de la Guyane (UAG)-École des hautes études en sciences sociales (EHESS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de La Réunion (UR)-Université de la Polynésie Française (UPF)-Université de la Nouvelle-Calédonie (UNC)-Institut d'écologie et environnement-Université des Antilles (UA), Centre Scientifique de Monaco (CSM), Tara Expéditions, Shimoda Marine Research Center, Université de Tsukuba = University of Tsukuba, University of Maine, 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 de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Géochrononologie Traceurs Archéométrie (GEOTRAC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Earth and Planetary Science [Rehovot], Weizmann Institute of Science [Rehovot, Israël], 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), Laboratoire d'Ecogéochimie des environnements benthiques (LECOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Océanographie Microbienne (LOMIC), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Center for Marine Environmental Sciences [Bremen] (MARUM), Universität Bremen, Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-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), ECOlogy of MArine Plankton (ECOMAP), Adaptation et diversité en milieu marin (ADMM), Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), 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)-Station biologique de Roscoff (SBR), Ohio State University [Columbus] (OSU), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), National University of Ireland [Galway] (NUI Galway), Oregon State University (OSU), University of Konstanz, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-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 d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Duke University [Durham], Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Marine Chemistry and Geochemistry (WHOI), Woods Hole Oceanographic Institution (WHOI), Évolution, génomes, comportement et écologie (EGCE), Université Paris-Sud - Paris 11 (UP11)-IRD-Centre National de la Recherche Scientifique (CNRS), Department of Earth Sciences [USC Los Angeles], University of Southern California (USC), Martin Ryan Institute, Laboratoire d'Océanographie et du Climat : Expérimentations et Approches Numériques (LOCEAN), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Derby [United Kingdom], Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-17-CE02-0020,CORALGENE,Complexité génomique de l'holobionte ' corail ' à l'échelle du Pacifique(2017), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université des Antilles (UA)-Institut d'écologie et environnement-Université de la Nouvelle-Calédonie (UNC)-Université de la Polynésie Française (UPF)-Université de La Réunion (UR)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Université des Antilles et de la Guyane (UAG)-Institut de Recherche pour le Développement (IRD), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Banyuls (OOB), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-IRD-Université Paris-Sud - Paris 11 (UP11), Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Justus-Liebig-Universität Gießen (JLU), Institut Universitaire Européen de la Mer (IUEM), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)
Subjects: 0301 basic medicine, Topography, Coral reefs, Effects of global warming on oceans, Coral, Biodiversity, Marine and Aquatic Sciences, Ecosystem services, 0302 clinical medicine, Community Page, Oceans, Biology (General), Islands, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, geography.geographical_feature_category, Ecology, Microbiota, General Neuroscience, Eukaryota, Coral reef, Anthozoa, Plankton, Holobiont, Corals, Expeditions, General Agricultural and Biological Sciences, Marine ecosystems, QH301-705.5, Climate change, Marine Biology, Biology, Ecosystems, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, ddc:570, Animals, Metabolomics, Marine ecosystem, 14. Life underwater, Symbiosis, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, Landforms, geography, Pacific Ocean, General Immunology and Microbiology, ACL, Ecology and Environmental Sciences, Organisms, Biology and Life Sciences, Geomorphology, Bodies of Water, 15. Life on land, Invertebrates, 030104 developmental biology, 13. Climate action, Earth Sciences, Reefs, Metagenomics, Reef ecosystems, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, 030217 neurology & neurosurgery
Abstract: Coral reefs are the most diverse habitats in the marine realm. Their productivity, structural complexity, and biodiversity critically depend on ecosystem services provided by corals that are threatened because of climate change effects—in particular, ocean warming and acidification. The coral holobiont is composed of the coral animal host, endosymbiotic dinoflagellates, associated viruses, bacteria, and other microeukaryotes. In particular, the mandatory photosymbiosis with microalgae of the family Symbiodiniaceae and its consequences on the evolution, physiology, and stress resilience of the coral holobiont have yet to be fully elucidated. The functioning of the holobiont as a whole is largely unknown, although bacteria and viruses are presumed to play roles in metabolic interactions, immunity, and stress tolerance. In the context of climate change and anthropogenic threats on coral reef ecosystems, the Tara Pacific project aims to provide a baseline of the “-omics” complexity of the coral holobiont and its ecosystem across the Pacific Ocean and for various oceanographically distinct defined areas. Inspired by the previous Tara Oceans expeditions, the Tara Pacific expedition (2016–2018) has applied a pan-ecosystemic approach on coral reefs throughout the Pacific Ocean, drawing an east–west transect from Panama to Papua New Guinea and a south–north transect from Australia to Japan, sampling corals throughout 32 island systems with local replicates. Tara Pacific has developed and applied state-of-the-art technologies in very-high-throughput genetic sequencing and molecular analysis to reveal the entire microbial and chemical diversity as well as functional traits associated with coral holobionts, together with various measures on environmental forcing. This ambitious project aims at revealing a massive amount of novel biodiversity, shedding light on the complex links between genomes, transcriptomes, metabolomes, organisms, and ecosystem functions in coral reefs and providing a reference of the biological state of modern coral reefs in the Anthropocene., This Community Page article presents the Tara Pacific expedition, which aims to shed light on the complex links between genomes, transcriptomes, metabolomes, organisms, and ecosystem functions in coral reefs, and providing a reference of the biological state of modern reef systems.
Published: 2019
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15. PGC1α Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness

Author: Emilie Jaune, Stephan Clavel, Jean-François Tanti, Frédéric Bost, Nicolas Nottet, Kathiane Laurent, Matthieu Durand, Maeva Dufies, Maeva Gesson, Stéphane Rocchi, Lisa Kaminski, J. F. Michiels, Damien Ambrosetti, Issam Ben-Sahra, Romain Haider, Stéphanie Torrino, Nathalie M. Mazure, Francois Rene Roustan, Zied Djabari, Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, 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), 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 Scientifique de Monaco (CSM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Musee oceanographique de Monaco, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), 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), Hôpital Pasteur [Nice] (CHU), U1065 Centre Méditerranéen de Médecine Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de signalisation, biologie du développement et cancer (ISBDC), Laboratoire des Bio-Indicateurs Actuels et Fossiles (BIAF), Université d'Angers (UA), Northwestern University Chicago, Signalisation moléculaire et obésité, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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 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), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Bio-Indicateurs Actuels et Fossiles (BIAF), Northwestern University [Chicago, Ill. USA], 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)
Subjects: Male, 0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Apoptosis, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, Mitochondrial Membrane Transport Proteins, Metastasis, Ornithine decarboxylase, Mice, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Polyamines, Tumor Cells, Cultured, Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Dicarboxylic Acid Transporters, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mitochondria, Gene Expression Regulation, Neoplastic, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Signal Transduction, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Downregulation and upregulation, Coactivator, Biomarkers, Tumor, medicine, Animals, Humans, Aged, Cell Proliferation, Prostatic Neoplasms, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, chemistry, Cancer cell, Cancer research, Polyamine, Carcinogenesis, Follow-Up Studies
Abstract: Although tumorigenesis is dependent on the reprogramming of cellular metabolism, the metabolic pathways engaged in the formation of metastases remain largely unknown. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) plays a pleiotropic role in the control of cancer cell metabolism and has been associated with a good prognosis in prostate cancer. Here, we show that PGC1α represses the metastatic properties of prostate cancer cells via modulation of the polyamine biosynthesis pathway. Mechanistically, PGC1α inhibits the expression of c-MYC and ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme for polyamine synthesis. Analysis of in vivo metastases and clinical data from patients with prostate cancer support the proposition that the PGC1α/c-MYC/ODC1 axis regulates polyamine biosynthesis and prostate cancer aggressiveness. In conclusion, downregulation of PGC1α renders prostate cancer cells dependent on polyamine to promote metastasis. Significance: These findings show that a major regulator of mitochondrial metabolism controls polyamine synthesis and prostate cancer aggressiveness, with potential applications in therapy and identification of new biomarkers.
Published: 2019
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16. VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness

Author: Sandy Giuliano, Natacha Glisse, Gilles Pagès, Laetitia Douguet, Papa Diogop Ndiaye, Damien Ambrosetti, Valérie Vouret-Craviari, Baharia Mograbi, Maeva Dufies, Philippe Lenormand, Maud Wurmser, Nathalie Rioux-Leclercq, Pascal Maire, Jérôme Durivault, Janita Mintcheva, Renaud Grépin, 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), Centre Scientifique de Monaco (CSM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 )
Subjects: 0301 basic medicine, renal cell carcinoma, VEGFC Gene, Angiogenesis, sunitinib, Transplantation, Heterologous, Vascular Endothelial Growth Factor C, Cell, VEGFC, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Metastasis, Mice, 03 medical and health sciences, angiogenesis, 0302 clinical medicine, Cell Line, Tumor, medicine, Animals, Humans, metastasis, Carcinoma, Renal Cell, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), CRISPR/Cas9, ComputingMilieux_MISCELLANEOUS, Reporter gene, Akt/PKB signaling pathway, Gene Expression Profiling, medicine.disease, 3. Good health, Lymphangiogenesis, lymphangiogenesis, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Vascular endothelial growth factor C, 030220 oncology & carcinogenesis, Cancer research, Neoplasm Transplantation, Research Paper
Abstract: Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network is dependent on vascular endothelial growth factor C (VEGFC) and lies at the front line of metastatic spreading. Here, we addressed the role of VEGFC in RCC aggressiveness and the regulation of its expression in hypoxia. Methods: Transcriptional and post transcriptional regulation of VEGFC expression was evaluated by qPCR and with reporter genes. The involvement of HIF was evaluated using a siRNA approach. Experimental RCC were performed with immuno-competent/deficient mice using human and mouse cells knocked-out for the VEGFC gene by a CRISPR/Cas9 method. The VEGFC axis was analyzed with an online available data base (TCGA) and using an independent cohort of patients. Results: Hypoxia induced VEGFC protein expression but down-regulated VEGFC gene transcription and mRNA stability. Increased proliferation, migration, over-activation of the AKT signaling pathway and enhanced expression of mesenchymal markers characterized VEGFC-/- cells. VEGFC-/- cells did not form tumors in immuno-deficient mice but developed aggressive tumors in immuno-competent mice. These tumors showed down-regulation of markers of activated lymphocytes and M1 macrophages, and up-regulation of M2 macrophages markers and programmed death ligand 1 (PDL1). Over-expression of lymphangiogenic genes including VEGFC was linked to increased disease-free and overall survival in patients with non-metastatic tumors, whereas its over-expression correlated with decreased progression-free and overall survival of metastatic patients. Conclusion: Our study revisited the admitted dogma linking VEGFC to tumor aggressiveness. We conclude that targeting VEGFC for therapy must be considered with caution.
Published: 2019
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17. Flow-driven micro-scale pH variability affects the physiology of corals and coralline algae under ocean acidification

Author: Malcolm T. McCulloch, C. Alessi, R. Trehern, Christopher E. Cornwall, Chloé A. Pupier, Thomas M. DeCarlo, Steeve Comeau, The University of Western Australia (UWA), 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), Victoria University of Wellington, and Centre Scientifique de Monaco (CSM)
Subjects: 0301 basic medicine, Light, Oceans and Seas, Carbonates, lcsh:Medicine, Photosynthesis, Article, Diffusion, Environmental impact, 03 medical and health sciences, Calcification, Physiologic, 0302 clinical medicine, Dissolved organic carbon, Animals, 14. Life underwater, Natural variability, lcsh:Science, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, Marine biology, Multidisciplinary, biology, Chemistry, lcsh:R, Climate-change ecology, Eukaryota, Coralline algae, Ocean acidification, Hydrogen-Ion Concentration, Anthozoa, biology.organism_classification, 030104 developmental biology, Flow velocity, 13. Climate action, Environmental chemistry, lcsh:Q, Seawater, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Rheology, Saturation (chemistry), Acids, 030217 neurology & neurosurgery
Abstract: Natural variability in pH in the diffusive boundary layer (DBL), the discrete layer of seawater between bulk seawater and the outer surface of organisms, could be an important factor determining the response of corals and coralline algae to ocean acidification (OA). Here, two corals with different morphologies and one coralline alga were maintained under two different regimes of flow velocities, pH, and light intensities in a 12 flumes experimental system for a period of 27 weeks. We used a combination of geochemical proxies, physiological and micro-probe measurements to assess how these treatments affected the conditions in the DBL and the response of organisms to OA. Overall, low flow velocity did not ameliorate the negative effect of low pH and therefore did not provide a refugia from OA. Flow velocity had species-specific effects with positive effects on calcification for two species. pH in the calcifying fluid (pHcf) was reduced by low flow in both corals at low light only. pHcf was significantly impacted by pH in the DBL for the two species capable of significantly modifying pH in the DBL. The dissolved inorganic carbon in the calcifying fluid (DICcf) was highest under low pH for the corals and low flow for the coralline, while the saturation state in the calcifying fluid and its proxy (FWHM) were generally not affected by the treatments. This study therefore demonstrates that the effects of OA will manifest most severely in a combination of lower light and lower flow habitats for sub-tropical coralline algae. These effects will also be greatest in lower flow habitats for some corals. Together with existing literature, these findings reinforce that the effects of OA are highly context dependent, and will differ greatly between habitats, and depending on species composition.
Published: 2019
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18. New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments

Author: Dufies, Maeva, Grytsai, Oleksandr, Ronco, Cyril, Camara, Oumar, Ambrosetti, Damien, Hagege, Anaïs, Parola, Julien, Mateo, Lou, Ayrault, Marion, Giuliano, Sandy, Grépin, Renaud, Lagarde, Nathalie, Montes, Matthieu, Auberger, Patrick, Demange, Luc, Benhida, Rachid, Pagès, Gilles, Centre Scientifique de Monaco (CSM), 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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), 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), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire Génomique, bioinformatique et chimie moléculaire (GBCM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre méditerranéen 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)-Université Côte d'Azur (UCA), Puybonnieux, Aurélie, Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)
Subjects: Cell Survival, Antineoplastic Agents, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, urologic and male genital diseases, Receptors, Interleukin-8B, Receptors, Interleukin-8A, Inhibitory Concentration 50, Mice, angiogenesis, Head and Neck Squamous Cell Carcinoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Cell Line, Tumor, Animals, Humans, ELR+CXCL cytokines, CXCR1/2 inhibitor, neoplasms, Cell Proliferation, Clear cell Renal Cell Carcinoma, Prognosis, ELR + CXCL cytokines, Xenograft Model Antitumor Assays, Kidney Neoplasms, female genital diseases and pregnancy complications, Molecular Docking Simulation, stomatognathic diseases, Head and Neck Neoplasms, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Signal Transduction
Abstract: International audience; Clear cell Renal Cell (RCC) and Head and Neck Squamous Cell Carcinomas (HNSCC) are characterized by a pro-angiogenic/pro-inflammatory context. Despite conventional or targeted therapies, metastatic RCC and HNSCC remain incurable. Alternative treatments to reference therapies (sunitinib, a multi tyrosine kinase inhibitor for RCC or cisplatin for HNSCC) are urgently needed on relapse. Here, we described the relevance of targeting the ELR+CXCL cytokines receptors, CXCR1/2, for the treatment of these two cancer types.Methods: The relevance to patient treatment was evaluated by correlating the ELR+CXCL/CXCR1/2 levels to survival using online available data. We report herein the synthesis of new pharmacological inhibitors of CXCR1/2 with anti-proliferation/survival activity. The latter was evaluated with the XTT assay with leukemic, breast, RCC and HNSCC cell lines. Their relevance as an alternative treatment was tested on sunitinib- and cisplatin- resistant cells. The most efficient compound was then tested in a mouse model of RCC and HNSCC.Results: RCC and HNSCC expressed the highest amounts of CXCR1/2 of all cancers. High levels of ELR+CXCL cytokines (CXCL1, 2, 3, 5, 6, 7, 8) correlated to shorter survival. Among the 33 synthesized and tested molecules, compound C29 reduced ELR+CXCL/CXCR1/2-dependent proliferation and migration of endothelial cells. C29 exerted an anti-proliferation/survival activity on a panel of cancer cells including naive and resistant RCC and HNSCC cells. C29 reduced the growth of experimental RCC and HNSCC tumors by decreasing tumor cell proliferation, angiogenesis and ELR+/CXCL-mediated inflammation.Conclusion: Our study highlights the relevance of new CXCR1/2 inhibitors for the treatment of RCC or HNSCC as first-line treatment or at relapse on reference therapies.
Published: 2019
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19. Human Health and Ocean Pollution

Author: Luigi Vezzulli, Mark E. Hahn, Samantha Fisher, Patrick Fénichel, Michael H. Depledge, Ariana Zeka, Lorraine C. Backer, Amro Hamdoun, Jacqueline McGlade, F. Brucker-Davis, Patrick Rampal, Laura Giuliano, Hervé Raps, John J. Stegeman, Christopher M. Reddy, Denis Allemand, Maria Luiza Pedrotti, Nicolas Chevalier, Philipp Hess, Donald M. Anderson, Jenna Mu, François Galgani, Charles J. Dorman, Lilian Corra, Gabriella Taghian, Lora E. Fleming, Jeroen A. J. M. van de Water, Bret Judson, Pal Weihe, Marie-Yasmine Dechraoui Bottein, Françoise Gaill, Amalia Laborde, Hariharan Shanmugam, Maria Neira, Joacim Rocklöv, Dimitri D. Deheyn, William H. Gaze, Dorota Czerucka, Ursula M. Scharler, Adetoun Mustapha, Philippe Grandjean, Barbara A. Demeneix, Philip J. Landrigan, Rachel T. Noble, Boston College (BC), Woods Hole Oceanographic Institution (WHOI), University of Exeter Medical School, University of Exeter, Centre Scientifique de Monaco (CSM), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Centre Hospitalier Universitaire de Nice (CHU Nice), Global Alliance on Health and Pollution (GAHP), United Nations Educational, Scientific and Cultural Organization (UNESCO), Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN), University of California [San Diego] (UC San Diego), University of California, Trinity College Dublin, Université Côte d'Azur (UCA), Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), The Mediterranean Science Commission (CIESM), Harvard University [Cambridge], Universidad de la República (UDELAR), University College of London [London] (UCL), Imperial College London, World Health Organization [Niamey], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), 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), Umeå University, University of KwaZulu-Natal (UKZN), University of Genoa (UNIGE), University of the Faroe Islands, Brunel University London [Uxbridge], University of California (UC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Harvard University, Universidad de la República [Montevideo] (UDELAR), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), and Università degli studi di Genova = University of Genoa (UniGe)
Subjects: Male, Pollution, Oceans and Seas, media_common.quotation_subject, Review, Infectious and parasitic diseases, RC109-216, 12. Responsible consumption, Marine pollution, 03 medical and health sciences, 0302 clinical medicine, Environmental protection, 11. Sustainability, Animals, Humans, Seawater, Marine ecosystem, 030212 general & internal medicine, 14. Life underwater, Water pollution, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, Ecosystem, media_common, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Pollutant, 030503 health policy & services, Water Pollution, fungi, Global warming, Ocean acidification, General Medicine, Hydrogen-Ion Concentration, 15. Life on land, Miljövetenskap, 6. Clean water, 13. Climate action, Environmental science, Public aspects of medicine, RA1-1270, 0305 other medical science, Plastic pollution, Plastics, Environmental Sciences
Abstract: Copyright © 2020 The Author(s). Background: Pollution – unwanted waste released to air, water, and land by human activity – is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health. Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources – coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. Ecosystem Findings: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the Vibrio species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. Human Health Findings: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants in utero to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children’s risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals – phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste – can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that Vibrio infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South – environmental injustice on a planetary scale. Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth’s resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted. Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored. Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries. Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health. Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress. Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries. Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas. The Centre Scientifique de Monaco, the Prince Albert II of Monaco Foundation and the Government of the Principality of Monaco John J. Stegeman is supported by U.S. Oceans and Human Health Program (NIH grant P01ES028938 and National Science Foundation grant OCE-1840381). Lora E. Fleming is supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 774567 (H2020 SOPHIE Project) and No 666773 (H2020 BlueHealth Project). Plastic toxicity research for Dimitri Deheyn is supported by the BEST Initiative (https://deheynlab.ucsd.edu/best-2/). Barbara Demeneix is supported by grants from the program H2020. Charles J. Dorman is supported by Science Foundation Ireland Investigator Award 13/IA/1875. William H. Gaze is supported by a Natural Environment Research Council Knowledge Exchange Fellowship NE/S006257/1 on the environmental dimension of antimicrobial resistance. Philippe Grandjean is supported by National Institute of Environmental Health Sciences (NIEHS) of the NIH (grant No. ES027706), a Superfund center grant for the Sources, Transport, Exposure and Effects of Perfluoroalkyl Substances (STEEP) Center. Mark E. Hahn is supported by U.S. Oceans and Human Health Program (NIH grant P01ES028938 and National Science Foundation grant OCE-1840381). Amro Hamdoun is supported by NIH and NSF Program on Oceans and Human Health Grants NIH ES030318 and NSF 1840844. Philipp Hess is supported by the IAEA Core Research Project K41014, by the European H2020 program for funding the EMERTOX project (grant number 778069), by the Atlantic Interreg (grant number Alertox-Net EAPA-317-2016) and by EFSA for the project EUROCIGUA (framework partnership agreement GP/EFSA/AFSCO/2015/03). Rachel T. Noble was supported by the US National Science Foundation Accelerating Innovations in Research #1602023 and the NOAA NERRS Science Collaborative. Maria Luiza Pedrotti is supported by Centre National de la Recherche Scientifique (CNRS). Luigi Vezzulli is supported by the following grants: European FP7 Program Grant AQUAVALENS 311846 and European Union’s Horizon 2020 Research and Innovation Program Grant VIVALDI 678589. Pál Weihe is supported by the Danish EPA programme: Danish Cooperation for Environment in the Arctic and by the Faroese Research Council.
Published: 2020
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20. Effects of ultraviolet radiation and nutrient level on the physiological response and organic matter release of the scleractinian coral Pocillopora damicornis following thermal stress

Author: Fanny Houlbrèque, Lucile Courtial, Victor Planas Bielsa, Christine Ferrier-Pagès, Sorbonne Université (SU), Ecologie marine tropicale dans les Océans Pacifique et Indien (ENTROPIE [Réunion]), Institut de Recherche pour le Développement (IRD)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), and Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Institut de Recherche pour le Développement (IRD)
Subjects: Chlorophyll, Pigments, 0106 biological sciences, Hot Temperature, Chloroplasts, 010504 meteorology & atmospheric sciences, Physiology, Coral, Marine and Aquatic Sciences, lcsh:Medicine, Plant Science, Global Warming, Biochemistry, 01 natural sciences, Nutrient, Medicine and Health Sciences, Photosynthesis, lcsh:Science, Materials, Multidisciplinary, geography.geographical_feature_category, biology, Coral Reefs, Plant Biochemistry, Chemistry, Physics, Chemical Reactions, Classical Mechanics, Coral reef, Anthozoa, Environmental chemistry, Corals, Physical Sciences, Mechanical Stress, Bleaching, population characteristics, Cellular Structures and Organelles, Cellular Types, geographic locations, Research Article, Nitrogen, Ultraviolet Rays, Coral bleaching, Plant Cell Biology, Materials Science, Marine Biology, Pocillopora damicornis, Calcification, Calcification, Physiologic, Sea Water, Plant Cells, Animals, Seawater, 14. Life underwater, Reef, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, 0105 earth and related environmental sciences, geography, Organic Pigments, 010604 marine biology & hydrobiology, Ecology and Environmental Sciences, lcsh:R, fungi, technology, industry, and agriculture, Biology and Life Sciences, Aquatic Environments, Biogeochemistry, Nutrients, Cell Biology, 15. Life on land, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Marine Environments, Thermal Stresses, 13. Climate action, Earth Sciences, Reefs, lcsh:Q, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Physiological Processes, Eutrophication
Abstract: International audience; Understanding which factors enhance or mitigate the impact of high temperatures on corals is crucial to predict the severity of coral bleaching worldwide. On the one hand, global warming is usually associated with high ultraviolet radiation levels (UVR), and surface water nutrient depletion due to stratification. On the other hand, eutrophication of coastal reefs increases levels of inorganic nutrients and decreases UVR, so that the effect of different combinations of these stressors on corals is unknown. In this study, we assessed the individual and crossed effects of high temperature, UVR and nutrient level on the key performance variables of the reef building coral Pocillopora damicornis. We found that seawater warming was the major stressor, which induced bleaching and impaired coral photosynthe-sis and calcification in all nutrient and UVR conditions. The strength of this effect however, was nutrient dependent. Corals maintained in nutrient-depleted conditions experienced the highest decrease in net photosynthesis under thermal stress, while nutrient enrichment (3 μM NO 3-and 1 μM PO 4 +) slightly limited the negative impact of temperature through enhanced protein content, photosynthesis and respiration rates. UVR exposure had only an effect on total nitrogen release rates, which significantly decreased under normal growth conditions and tended to decrease also under thermal stress. This result suggests that increased level of UVR will lead to significant changes in the nutrient biogeochemistry of surface reef waters. Overall, our results show that environmental factors have different and interactive effects on each of the coral's physiological parameters, requiring multifactorial approaches to predict the future of coral reefs.
Published: 2018
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21. Ocean pH fluctuations affect mussel larvae at key developmental transitions

Author: A. Miglioli, Lydia Kapsenberg, Jean-Pierre Gattuso, Mark C. Bitter, Eric Tambutté, Rémi Dumollard, National Science Foundation (US), European Commission, Department of Education (US), Università degli studi di Genova, Observatoire Océanologique de Villefranche sur Mer, 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), Universita degli studi di Genova, University of Chicago, Centre Scientifique de Monaco (CSM), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), and Sciences Po (Sciences Po)
Subjects: 0106 biological sciences, 010504 meteorology & atmospheric sciences, Carbonates, ocean acidification, 01 natural sciences, chemistry.chemical_compound, trochophore, mollusc, General Environmental Science, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Larva, 4. Education, Ocean acidification, General Medicine, Hydrogen-Ion Concentration, Trochophore, Oceanography, Carbonate, Mollusc, Shell field, General Agricultural and Biological Sciences, Research Article, Development and Physiology, pH fluctuations, [SDE.MCG]Environmental Sciences/Global Changes, Climate Change, Context (language use), Development, General Biochemistry, Genetics and Molecular Biology, Animals, Marine ecosystem, Seawater, 14. Life underwater, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, development, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, 0105 earth and related environmental sciences, Mytilus, General Immunology and Microbiology, 010604 marine biology & hydrobiology, fungi, Mussel, [SDE.ES]Environmental Sciences/Environmental and Society, shell field, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, chemistry, 13. Climate action, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology
Abstract: 10 pages, 4 figures, supplementary material https://dx.doi.org/10.6084/m9.figshare.c.4325828.-- Data are archived on BCO-DMO, https://www.bco-dmo.org/project/720349, Coastal marine ecosystems experience dynamic fluctuations in seawater carbonate chemistry. The importance of this variation in the context of ocean acidification requires knowing what aspect of variability biological processes respond to. We conducted four experiments (ranging from 3 to 22 days) with different variability regimes (pHT 7.4–8.1) assessing the impact of diel fluctuations in carbonate chemistry on the early development of the mussel Mytilus galloprovincialis. Larval shell growth was consistently correlated to mean exposures, regardless of variability regimes, indicating that calcification responds instantaneously to seawater chemistry. Larval development was impacted by timing of exposure, revealing sensitivity of two developmental processes: development of the shell field, and transition from the first to the second larval shell. Fluorescent staining revealed developmental delay of the shell field at low pH, and abnormal development thereof was correlated with hinge defects in D-veligers. This study shows, for the first time, that ocean acidification affects larval soft-tissue development, independent from calcification. Multiple developmental processes additively underpin the teratogenic effect of ocean acidification on bivalve larvae. These results explain why trochophores are the most sensitive life-history stage in marine bivalves and suggest that short-term variability in carbonate chemistry can impact early, This research was funded by the US National Science Foundation (NSF; OCE-1521597 to L.K.). L.K. was also supported by the European Commission Horizon 2020 Marie Skłodowska-Curie Action (No. 747637). M.C.B. was supported by US Department of Education (Grant No. 200A150101) and NSF Graduate Research Fellowship (No. 1000198423). A.M. was supported by an Erasmus+ traineeship scholarship (University of Genova) and by the Observatoire Océanologique de Villefranche
Published: 2018
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22. Coral bleaching is linked to the capacity of the animal host to supply essential metals to the symbionts

Author: Christine Ferrier-Pagès, Lucie Sauzéat, Vincent Balter, Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement [Lyon] (LGL-TPE), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and Centre Scientifique de Monaco (CSM)
Subjects: 0106 biological sciences, 0301 basic medicine, Coral bleaching, Coral, [SDE.MCG]Environmental Sciences/Global Changes, Heterotroph, Stylophora pistillata, global warming, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, Nutrient, Stress, Physiological, Anthozoa, Environmental Chemistry, Animals, Seawater, 14. Life underwater, Symbiosis, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, General Environmental Science, Trophic level, Global and Planetary Change, heterotrophy, Ecology, biology, Chemistry, fungi, technology, industry, and agriculture, coral bleaching, Heterotrophic Processes, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, zinc isotope, essential metals, 030104 developmental biology, copper isotope, 13. Climate action, Metals, [SDU]Sciences of the Universe [physics], population characteristics, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology, geographic locations, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Massive coral bleaching events result in extensive coral loss throughout the world. These events are mainly caused by seawater warming, but are exacerbated by the subsequent decrease in nutrient availability in surface waters. It has therefore been shown that nitrogen, phosphorus or iron limitation contribute to the underlying conditions by which thermal stress induces coral bleaching. Generally, information on the trophic ecology of trace elements (micronutrients) in corals, and on how they modulate the coral response to thermal stress is lacking. Here, we demonstrate for the first time that heterotrophic feeding (i.e. the capture of zooplankton prey by the coral host) and thermal stress induce significant changes in micro element concentrations and isotopic signatures of the scleractinian coral Stylophora pistillata. The results obtained first reveal that coral symbionts are the major sink for the heterotrophically acquired micronutrients and accumulate manganese, magnesium and iron from the food. These metals are involved in photosynthesis and antioxidant protection. In addition, we show that fed corals can maintain high micronutrient concentrations in the host tissue during thermal stress and do not bleach, whereas unfed corals experience a significant decrease in copper, zinc, boron, calcium and magnesium in the host tissue and bleach. In addition, the significant increase in δ65Cu and δ66Zn signature of symbionts and host tissue at high temperature suggests that these isotopic compositions are good proxy for stress in corals. Overall, present findings highlight a new way in which coral heterotrophy and micronutrient availability contribute to coral resistance to global warming and bleaching
Published: 2018
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23. Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging

Author: Mathieu Pernot, Anikitos Garofalakis, Thomas Viel, Judith Favier, Mailyn Perez-Liva, Bertrand Tavitian, Jacques Pouysségur, Mafalda Correia, Mickael Tanter, Damien Bouda, Johanna Chiche, Charlotte Lussey-Lepoutre, B. Berthon, Jean Provost, Joevin Sourdon, Institut Langevin - Ondes et Images (UMR7587) (IL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe 'Contrôle Métabolique des Morts Cellulaires' (INSERM U1065 - C3M), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), 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), Département de Biologie Médicale [Centre Scientifique de Monaco], Centre scientifique de Monaco (CSM), Département de Radiologie Cardiovasculaire [AP-HP Hôpital Européen Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), ANR-11-INBS-0006,FLI,France Life Imaging(2011), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Tavitian, Bertrand, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut Langevin ondes et images, Centre National de la Recherche Scientifique ( CNRS ) -ESPCI ParisTech-Université Paris Diderot - Paris 7 ( UPD7 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département de Médecine Nucléaire [AP-HP Hôpital Pitié-Salpétrière], CHU Pitié-Salpêtrière [APHP], Equipe 'Contrôle Métabolique des Morts Cellulaires' ( INSERM U1065 - C3M ), Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Recherche sur le Cancer et le Vieillissement ( IRCAN ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), ANR-11-INBS-0006/11-INBS-0006,FLI,France In vivo Imaging ( 2011 ), and ANR-10-IDEX-0001-02/10-LABX-0024,WIFI,Institut Langevin : Ondes et Images, du Fondamental à l'Innovation ( 2010 )
Subjects: 0301 basic medicine, Materials science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, 030218 nuclear medicine & medical imaging, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Cricetinae, Neoplasms, Positron Emission Tomography Computed Tomography, medicine, Animals, Positron emission, Rats, Wistar, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Ultrasonography, medicine.diagnostic_test, business.industry, Myocardium, Ultrasound, Heart, Frame rate, Rats, Computer Science Applications, Functional imaging, Glucose, Phenotype, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Positron emission tomography, Female, Ultrasonic sensor, Tomography, Molecular imaging, business, Biotechnology, Biomedical engineering
Abstract: International audience; Positron emission tomography–computed tomography (PET–CT) is the most sensitive molecular imaging modality, but it does not easily allow for rapid temporal acquisition. Ultrafast ultrasound imaging (UUI)—a recently introduced technology based on ultrasonic holography—leverages frame rates of up to several thousand images per second to quantitatively map, at high resolution, haemodynamic, biomechanical, electrophysiological and structural parameters. Here, we describe a pre-clinical scanner that registers PET–CT and UUI volumes acquired simultaneously and offers multiple combinations for imaging. We demonstrate that PET–CT–UUI allows for simultaneous images of the vasculature and metabolism during tumour growth in mice and rats, as well as for synchronized multi-modal cardiac cine-loops. Combined anatomical, functional and molecular imaging with PET–CT–UUI represents a high-performance and clinically translatable technology for biomedical research.
Published: 2018
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24. Evidence for mitigation of coral bleaching by manganese

Author: Biscéré, Tom, Ferrier-Pagès, Christine, Gilbert, Antoine, Pichler, Thomas, Houlbrèque, Fanny, Sorbonne Université (SU), Ecologie marine tropicale des océans Pacifique et Indien (ENTROPIE [Nouvelle-Calédonie]), Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Ifremer - Nouvelle-Calédonie, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de la Nouvelle-Calédonie (UNC), Centre Scientifique de Monaco (CSM), and Universität Bremen
Subjects: Manganese, Iron, lcsh:R, fungi, lcsh:Medicine, Anthozoa, Global Warming, Article, Calcification, Physiologic, Metals, Stress, Physiological, Animals, Water Pollutants, lcsh:Q, [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, Photosynthesis, Symbiosis, lcsh:Science, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography
Abstract: International audience; Unprecedented mass coral bleaching events due to global warming and overall seawater pollution have been observed worldwide over the last decades. Although metals are often considered as toxic substances for corals, some are essential at nanomolar concentrations for physiological processes such as photosynthesis and antioxidant defenses. This study was designed to elucidate, the individual and combined effects of nanomolar seawater enrichment in manganese (Mn) and iron (Fe), on the main physiological traits of Stylophora pistillata, maintained under normal growth and thermal stress conditions. We provide, for the first time, evidence that Mn is a key trace element for coral symbionts, enhancing cellular chlorophyll concentrations, photosynthetic efficiency and gross photosynthetic rates at ambient temperature. Our experiment also highlights the key role of Mn in increasing coral resistance to heat stress-induced bleaching. While Mn-enriched corals did not bleach and did not reduce their rates of photosynthesis and calcification, control corals experienced significant bleaching. On the contrary to Mn, Fe enrichment not only impaired calcification but induced significant bleaching. Such information is an important step towards a better understanding of the response of corals to seawater enrichment in metals. It can also explain, to some extent, species susceptibility to environmental stress.
Published: 2018
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25. ERK1 is dispensable for mouse pancreatic beta cell function but is necessary for glucose-induced full activation of MSK1 and CREB

Author: Jacques Pouysségur, Dany Muller, Safia Costes, Michele Leduc, Joy Richard, Gyslaine Bertrand, Vincent Compan, Jean-François Tanti, Julia Mathieu, Stéphane Dalle, Annie Varrault, Gilles Pagès, Magalie A. Ravier, 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), 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 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 Centre Scientifique de Monaco (CSM)
Subjects: 0301 basic medicine, medicine.medical_specialty, MSK1, Cell Survival, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biology, Pancreatic beta cell mass, CREB, Peri-insulitis, Ribosomal Protein S6 Kinases, 90-kDa, Cell Line, Islets of Langerhans, Mice, 03 medical and health sciences, 0302 clinical medicine, Insulin-Secreting Cells, Internal medicine, Internal Medicine, medicine, Extracellular, Animals, Insulin, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Beta (finance), Pancreatic islet biology, Mice, Knockout, Mitogen-Activated Protein Kinase 1, geography, Mitogen-Activated Protein Kinase 3, geography.geographical_feature_category, ERK1/2, Kinase, Insulin secretion, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Islet, Ageing, Glucose, 030104 developmental biology, Endocrinology, Cell culture, biology.protein, Calcium, Beta cell, p90RSK, 030217 neurology & neurosurgery
Abstract: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 −/− mice) and pharmacological approaches. NAD(P)H, free cytosolic Ca2+ concentration and insulin secretion were determined in islets. ERK1 and ERK2 subplasmalemmal translocation and activity was monitored using total internal reflection fluorescence microscopy. ERK1/2, mitogen and stress-activated kinase1 (MSK1) and cAMP-responsive element-binding protein (CREB) activation were evaluated by western blot and/or immunocytochemistry. The islet mass was determined from pancreatic sections. Glucose induced rapid subplasmalemmal recruitment of ERK1 and ERK2. When both ERK1 and ERK2 were inhibited simultaneously, the rapid transient peak of the first phase of glucose-induced insulin secretion was reduced by 40% (p
Published: 2017
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26. The Assimilation of Diazotroph-Derived Nitrogen by Scleractinian Corals Depends on Their Metabolic Status

Author: Vanessa N. Bednarz, Renaud Grover, Jean-Francois Maguer, Maoz Fine, Christine Ferrier-Pagès, Douglas G. Capone, Centre Scientifique de Monaco (CSM), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO), The Interuniversity Institute for marine Science in Eilat, Bar-Ilan University [Israël], Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, 0301 basic medicine, STYLOPHORA-PISTILLATA, MUCUS, Nitrogen, Coral, Heterotroph, DIVERSITY, Stylophora pistillata, 01 natural sciences, FIXATION ACETYLENE-REDUCTION, Microbiology, Phosphates, 03 medical and health sciences, Symbiosis, Virology, Nitrogen Fixation, FIXING CYANOBACTERIA, Botany, Animals, Seawater, 14. Life underwater, Autotroph, DINITROGEN FIXATION, Nitrogen cycle, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, biology, 010604 marine biology & hydrobiology, ACL, REEF, fungi, technology, industry, and agriculture, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Anthozoa, QR1-502, PHOSPHORUS, 030104 developmental biology, LIGHT, Prokaryotic Cells, Isotope Labeling, Nitrogen fixation, population characteristics, Diazotroph, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, N-2 FIXATION, geographic locations, Research Article
Abstract: Tropical corals are associated with a diverse community of dinitrogen (N2)-fixing prokaryotes (diazotrophs) providing the coral an additional source of bioavailable nitrogen (N) in oligotrophic waters. The overall activity of these diazotrophs changes depending on the current environmental conditions, but to what extent it affects the assimilation of diazotroph-derived N (DDN) by corals is still unknown. Here, in a series of 15N2 tracer experiments, we directly quantified DDN assimilation by scleractinian corals from the Red Sea exposed to different environmental conditions. We show that DDN assimilation strongly varied with the corals’ metabolic status or with phosphate availability in the water. The very autotrophic shallow-water (~5 m) corals showed low or no DDN assimilation, which significantly increased under elevated phosphate availability (3 µM). Corals that depended more on heterotrophy (i.e., bleached and deep-water [~45 m] corals) assimilated significantly more DDN, which contributed up to 15% of the corals’ N demand (compared to 1% in shallow corals). Furthermore, we demonstrate that a substantial part of the DDN assimilated by deep corals was likely obtained from heterotrophic feeding on fixed N compounds and/or diazotrophic cells in the mucus. Conversely, in shallow corals, the net release of mucus, rich in organic carbon compounds, likely enhanced diazotroph abundance and activity and thereby the release of fixed N to the pelagic and benthic reef community. Overall, our results suggest that DDN assimilation by corals varies according to the environmental conditions and is likely linked to the capacity of the coral to acquire nutrients from seawater., IMPORTANCE Tropical corals are associated with specialized bacteria (i.e., diazotrophs) able to transform dinitrogen (N2) gas into a bioavailable form of nitrogen, but how much of this diazotroph-derived nitrogen (DDN) is assimilated by corals under different environmental conditions is still unknown. Here, we used 15N2 labeling to trace the fate of DDN within the coral symbiosis. We show that DDN is assimilated by both the animal host and the endosymbiotic algae. In addition, the amount of assimilated DDN was significantly greater in mesophotic, bleached, or phosphorus-enriched corals than in surface corals, which almost did not take up this nitrogen form. DDN can thus be of particular importance for the nutrient budget of corals whenever they are limited by the availability of other forms of dissolved nutrients.
Published: 2017
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27. Marked phylogeographic structure of Gentoo penguin reveals an ongoing diversification process along the Southern Ocean

Author: Daniel González-Acuña, Daly Noll, Céline Le Bohec, Juliana A. Vianna, Gisele P. M. Dantas, Maria Virginia Petry, Andrés Barbosa, Elie Poulin, Francesco Bonadonna, Ministerio de Economía y Competitividad (España), Pontificia Universidad Católica de Chile (UC), Pontifícia Universidade Católica de Minas Gerais (PUC Minas), Universidade do Vale do Rio dos Sinos (UNISINOS), Departamento de Ecología Evolutiva (Museo Nacional de Ciencias Naturales), Museo Nacional de Ciencias Naturales (MNCN), Universidad de Concepción [Chile], Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-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 de Recherche pour le Développement (IRD [France-Sud]), Instituto de Ecología y Biodiversidad (IEB), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Musee oceanographique de Monaco, Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Universidad de Santiago de Chile [Santiago] (USACH), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, 0301 basic medicine, Polar region, Demographic history, Oceans and Seas, Biogeography, Biology, Population structure, DNA, Mitochondrial, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, Genetics, Animals, Climate change, 14. Life underwater, Molecular Biology, Phylogeny, Ecology, Evolution, Behavior and Systematics, Demography, Probability, Shetland, Ecology, Genetic Variation, Last Glacial Maximum, biology.organism_classification, Spheniscidae, Seabirds, Phylogeography, Genetics, Population, 030104 developmental biology, [SDE]Environmental Sciences, Genetic structure, Biological dispersal, Pygoscelis papua, Microsatellite Repeats
Abstract: Two main hypotheses have been debated about the biogeography of the Southern Ocean: (1) the Antarctic Polar Front (APF), acting as a barrier between Antarctic and sub-Antarctic provinces, and (2) the Antarctic Circumpolar Current (ACC), promoting gene flow among sub-Antarctic areas. The Gentoo penguin is distributed throughout these two provinces, separated by the APF. We analyzed mtDNA (HVR1) and 12 microsatellite loci of 264 Gentoo penguins, Pygoscelis papua, from 12 colonies spanning from the Western Antarctic Peninsula and the South Shetland Islands (WAP) to the sub-Antarctic Islands (SAI). While low genetic structure was detected among WAP colonies (mtDNA Ф = 0.037–0.133; microsatellite F = 0.009–0.063), high differentiation was found between all SAI and WAP populations (mtDNA Ф = 0.678–0.930; microsatellite F = 0.110–0.290). These results suggest that contemporary dispersal around the Southern Ocean is very limited or absent. As predicted, the APF appears to be a significant biogeographical boundary for Gentoo penguin populations; however, the ACC does not promote connectivity in this species. Our data suggest demographic expansion in the WAP during the last glacial maximum (LGM, about 20 kya), but stability in SAI. Phylogenetic analyses showed a deep divergence between populations from the WAP and those from the SAI. Therefore, taxonomy should be further revised. The Crozet Islands resulted as a basal clade (3.57 Mya), followed by the Kerguelen Islands (2.32 Mya) as well as a more recent divergence between the Falkland/Malvinas Islands and the WAP (1.27 Mya). Historical isolation, local adaptation, and past climate scenarios of those Evolutionarily Significant Units may have led to different potentials to respond to climate changes., The Spanish Ministry of Economy and Competitiveness supported sampling for the projects CGL2004-01348, CGL2007-60369, POL2006-06635 and CTM2011-24427.
Published: 2017
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28. Apparent changes in body insulation of juvenile king penguins suggest an energetic challenge during their early life at sea

Author: Henri Weimerskirch, Yvon Le Maho, Yves Handrich, Charles-André Bost, C. A. Bost, Manfred R. Enstipp, Céline Le Bohec, Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), Institut National de la Recherche Agronomique (INRA)-Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre Scientifique de Monaco (CSM), Musee oceanographique de Monaco, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Male, Physiology, Ontogeny, Diving, Foraging, Subcutaneous Fat, Aquatic Science, Molting, 010603 evolutionary biology, 01 natural sciences, Predation, Juvenile, Animals, 14. Life underwater, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Apex predator, Appetitive Behavior, biology, Ecology, 010604 marine biology & hydrobiology, Thermoregulation, biology.organism_classification, Aptenodytes patagonicus, Spheniscidae, Insect Science, [SDE]Environmental Sciences, Biological dispersal, Animal Science and Zoology, Female, Seasons, Body Temperature Regulation
Abstract: Little is known about the early life at sea of marine top predators, like deep-diving king penguins (Aptenodytes patagonicus), although this dispersal phase is probably a critical phase in their life. Apart from finding favourable foraging sites, they have to develop effective prey search patterns as well as physiological capacities that enable them to capture sufficient prey to meet their energetic needs. To investigate the ontogeny of their thermoregulatory responses at sea, we implanted 30 juvenile king penguins and 8 adult breeders with a small data logger that recorded pressure and subcutaneous temperature continuously for up to 2.5 years. We found important changes in the development of peripheral temperature patterns of foraging juvenile king penguins throughout their first year at sea. Peripheral temperature during foraging bouts fell to increasingly lower levels during the first 6 months at sea, after which it stabilized. Most importantly, these changes re-occurred during their second year at sea, after birds had fasted for ∼4 weeks on land during their second moult. Furthermore, similar peripheral temperature patterns were also present in adult birds during foraging trips throughout their breeding cycle. We suggest that rather than being a simple consequence of concurrent changes in dive effort or an indication of a physiological maturation process, these seasonal temperature changes mainly reflect differences in thermal insulation. Heat loss estimates for juveniles at sea were initially high but declined to approximately half after ∼6 months at sea, suggesting that juvenile king penguins face a strong energetic challenge during their early oceanic existence.
Published: 2017
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29. Heterotrophy promotes the re-establishment of photosynthate translocation in a symbiotic coral after heat stress

Author: Andrea Gori, Christine Ferrier-Pagès, Pascale Tremblay, Jean-François Maguer, Mia O. Hoogenboom, Centre Scientifique de Monaco (CSM), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), School of marine and tropical biology (Townsville, Australie), James Cook University (JCU), Tremblay, Pascale, Gori, Andrea, Maguer, Jean Françoi, Hoogenboom, Mia, Ferrier-Pagès, Christine, and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Hot Temperature, Light, Coral, ved/biology.organism_classification_rank.species, ocean acidification, Stylophora pistillata, 01 natural sciences, Photosynthesis, marine ecosystems, Scleractinian corals, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Autotrophic Processes, Multidisciplinary, biology, Turbinaria reniformis, Ecology, dinoflagellate symbiosis, bleached corals, Ocean acidification, Anthozoa, Autotrophic Processe, climate-change, Dinoflagellida, Symbiosi, Climate Change, Heterotroph, turbinaria-reniformis, thermal-stress, 010603 evolutionary biology, Article, Calcification, Physiologic, Photosynthesi, Botany, Animals, Marine ecosystem, 14. Life underwater, Autotroph, Symbiosis, stylophora-pistillata, Animal, ved/biology, ACL, 010604 marine biology & hydrobiology, fungi, Heterotrophic Processe, technology, industry, and agriculture, Dinoflagellate, Heterotrophic Processes, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Carbon, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Heat-Shock Response, organic-carbon fluxes
Abstract: Symbiotic scleractinian corals are particularly affected by climate change stress and respond by bleaching (losing their symbiotic dinoflagellate partners). Recently, the energetic status of corals is emerging as a particularly important factor that determines the corals’ vulnerability to heat stress. However, detailed studies of coral energetic that trace the flow of carbon from symbionts to host are still sparse. The present study thus investigates the impact of heat stress on the nutritional interactions between dinoflagellates and coral Stylophora pistillata maintained under auto- and heterotrophy. First, we demonstrated that the percentage of autotrophic carbon retained in the symbionts was significantly higher during heat stress than under non-stressful conditions, in both fed and unfed colonies. This higher photosynthate retention in symbionts translated into lower rates of carbon translocation, which required the coral host to use tissue energy reserves to sustain its respiratory needs. As calcification rates were positively correlated to carbon translocation, a significant decrease in skeletal growth was observed during heat stress. This study also provides evidence that heterotrophic nutrient supply enhances the re-establishment of normal nutritional exchanges between the two symbiotic partners in the coral S. pistillata, but it did not mitigate the effects of temperature stress on coral calcification.
Published: 2016
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30. Effect of salinity and temperature on the expression of genes involved in branchial ion transport processes in European sea bass

Author: Emilie Farcy, Waliullah Masroor, Alexander A. Venn, Eva Blondeau-Bidet, Eric Tambutté, Catherine Lorin-Nebel, MARine Biodiversity Exploitation and Conservation (UMR MARBEC), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut de Recherche pour le Développement (IRD), Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Centre Scientifique de Monaco (CSM), Université de Montpellier (UM), and Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Gills, 0106 biological sciences, chloride channel, Salinity, Physiology, 030310 physiology, Fresh Water, 01 natural sciences, Biochemistry, na+/k+-atpase, 0303 health sciences, Thermal acclimation, biology, Chemistry, Temperature, Cystic fibrosis transmembrane conductance regulator, cod gadus-morhua, Chloride channel, dicentrarchus-labrax, Ion transporter, cftr anion channel, General Agricultural and Biological Sciences, h+-atpase, 010603 evolutionary biology, Excretion, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Animals, Seawater, Dicentrarchus labrax, Na+/K+-ATPase, Sea bass, Ion Transport, seawater-acclimated medaka, functional classification, na+/k+/2cl(-) cotransporter, Membrane Transport Proteins, mRNA expression, Molecular biology, fresh-water, Gene Expression Regulation, biology.protein, Gill, Bass, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Cotransporter, Developmental Biology
Abstract: WOS:000497246100023; International audience; The responses of European sea bass to temperature increase and salinity decrease were investigated measuring mRNA expression levels of main genes involved in ion transport. Juvenile fish were pre-acclimated to seawater (SW) at 18 °C (temperate) or 24 °C (warm) for two weeks and then transferred for two weeks to either fresh water (FW) or SW at the respective temperature. Unlike temperate conditions, there is no change in Na+/K+-ATPase α1a (nka α1a) and Na+/H+ exchanger 3 (nhe3) mRNA expression following FW transfer in warm conditions. This is linked to the high expression of these genes in warm SW compared to temperate SW. Na+/Cl−-cotransporter (ncc2a) expression however is increased following FW transfer in temperate and warm conditions. Main transporters involved in ion excretion (Na+/K+/2Cl--1 cotransporter, nkcc1 and cystic fibrosis transmembrane conductance regulator, cftr) as well as nitrogen excretion (Rh-glycoproteins, rhcg1 and rhbg) and acid-base regulation (V-H+-ATPase, vha-a and b) are highly expressed in SW warm conditions vs FW warm. Overall, our results suggest a higher activation of ion transport processes in warm conditions and more strikingly in SW. This is linked to a strong interplay between diverse ion transporters in order to coordinate physiological responses at the gill level.
Published: 2019
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31. Full circumpolar migration ensures evolutionary unity in the Emperor penguin

Author: Daniel P. Zitterbart, André Ancel, Jason D. Whittington, Paul J. Ponganis, Céline Le Bohec, Yvon Le Maho, Andrea Benazzo, Phil Trathan, Enrico Zanetti, Giorgio Bertorelle, Emiliano Trucchi, Nils Christian Stenseth, Robin Cristofari, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centre Scientifique de Monaco (CSM), Department of Biology, Università degli Studi di Ferrara (UniFE), Center for Marine Biotechnology and Biomedicine, University of California, British Antarctic Survey (BAS), Natural Environment Research Council (NERC), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Woods Hole Oceanographic Institution (WHOI), Biophysics Laboratory University of Vienna, IPEV (programme 137), FP7-PEOPLE-IEF-2008, FP7-PEOPLE-IEF-2010, Centre Scientifique de Monaco, and ANR-10-BLAN-1728,PICASO,Les manchots bio-indicateurs de la vulnérabilité de l'Océan austral(2010)
Subjects: 0301 basic medicine, Male, Environmental change, [SDE.MCG]Environmental Sciences/Global Changes, Science, Climate Change, Population, Population Dynamics, Adaptation, Biological, extinction risk, General Physics and Astronomy, Antarctic Regions, Biology, Evolutionary ecology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Animals, 14. Life underwater, education, Population Density, education.field_of_study, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Multidisciplinary, Extinction, Genome, demographic survey, evolutionary biology, extinction risk, Ecology, Population size, Aptenodytes, Reproduction, evolutionary biology, Ecological genetics, Ambientale, demographic survey, General Chemistry, 15. Life on land, biology.organism_classification, Biological Evolution, Spheniscidae, 030104 developmental biology, Threatened species, Biological dispersal, Animal Migration, Female, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology, Climate-change impacts
Abstract: Defining reliable demographic models is essential to understand the threats of ongoing environmental change. Yet, in the most remote and threatened areas, models are often based on the survey of a single population, assuming stationarity and independence in population responses. This is the case for the Emperor penguin Aptenodytes forsteri, a flagship Antarctic species that may be at high risk continent-wide before 2100. Here, using genome-wide data from the whole Antarctic continent, we reveal that this top-predator is organized as one single global population with a shared demography since the late Quaternary. We refute the view of the local population as a relevant demographic unit, and highlight that (i) robust extinction risk estimations are only possible by including dispersal rates and (ii) colony-scaled population size is rather indicative of local stochastic events, whereas the species' response to global environmental change is likely to follow a shared evolutionary trajectory., Delimiting populations is crucial for conserving threatened species. Using genome-wide data from the whole of Antarctica, Cristofari et al. show that Emperor penguins are organised into a single global population that have shared demography since the late Quarternary.
Published: 2016
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32. Molecular assessment of the effect of light and heterotrophy in the scleractinian coral Stylophora pistillata

Author: Sarit Karako-Lampert, Oren Levy, Hiba Waldman Ben-Asher, Didier Zoccola, Christine Ferrier-Pagès, Gilles Pagès, Pagès, Gilles, The Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University [Israël], Département de Biologie Marine, Centre scientifique de Monaco (CSM), 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), This study was supported by the Scientific Center of Monaco,and was partially funded by the Israeli Science Foundation (grant no.243/10) to O. Levy, as well as by the Groupement de RechercheInternational Coral Reefs., and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: 0301 basic medicine, Light, Coral, [SDV]Life Sciences [q-bio], Heterotroph, Stylophora pistillata, Protein degradation, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Zooplankton, 03 medical and health sciences, Symbiosis, Botany, medicine, Animals, coral feeding, oxidative stress, 14. Life underwater, Autotroph, Photosynthesis, Research Articles, General Environmental Science, heterotrophy, General Immunology and Microbiology, biology, Coral Reefs, fungi, Heterotrophic Processes, General Medicine, bleaching, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Anthozoa, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, gene expression, General Agricultural and Biological Sciences, Transcriptome, microarray, Oxidative stress
Abstract: Corals acquire nutrients via the transfer of photosynthates by their endosymbionts (autotrophy), or via zooplankton predation by the animal (heterotrophy). During stress events, corals lose their endosymbionts, and undergo starvation, unless they increase their heterotrophic capacities. Molecular mechanisms by which heterotrophy sustains metabolism in stressed corals remain elusive. Here for the first time, to the best of our knowledge, we identified specific genes expressed in heterotrophically fed and unfed colonies of the scleractinian coral Stylophora pistillata , maintained under normal and light-stress conditions. Physiological parameters and gene expression profiling demonstrated that fed corals better resisted stress than unfed ones by exhibiting less oxidative damage and protein degradation. Processes affected in light-stressed unfed corals (HLU), were related to energy and metabolite supply, carbohydrate biosynthesis, ion and nutrient transport, oxidative stress, Ca 2+ homeostasis, metabolism and calcification (carbonic anhydrases, calcium-transporting ATPase, bone morphogenetic proteins). Two genes ( cp2u1 and cp1a2 ), which belong to the cytochrome P450 superfamily, were also upregulated 249 and 10 times, respectively, in HLU corals. In contrast, few of these processes were affected in light-stressed fed corals (HLF) because feeding supplied antioxidants and energetic molecules, which help repair oxidative damage. Altogether, these results show that heterotrophy helps prevent the cascade of metabolic problems downstream of oxidative stress.
Published: 2016
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33. On the use of P-31 NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae

Author: Olivier P. Thomas, Christine Ferrier-Pagès, Marc Gaysinski, Renaud Grover, Claire Godinot, Ecophysiologie des Cnidaires, Centre Scientifique de Monaco, Université Nice Sophia Antipolis Plate-Forme Technologique de Chimie, 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 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)-Avignon Université (AU), Département de Biologie Marine, Centre scientifique de Monaco (CSM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), and ~
Subjects: 0106 biological sciences, 0301 basic medicine, Magnetic Resonance Spectroscopy, Potassium Compounds, Coral, Liquid chromatography, Organophosphonates, Biology, Stylophora pistillata, 01 natural sciences, Article, Phosphates, 03 medical and health sciences, chemistry.chemical_compound, NMR spectroscopy, Anthozoa, Animals, Symbiosis, Multidisciplinary, 010604 marine biology & hydrobiology, Phosphorus, Nuclear magnetic resonance spectroscopy, Phosphate, biology.organism_classification, Culture Media, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Chemistry, 030104 developmental biology, chemistry, Biochemistry, Zooxanthellae, Glycerophosphates, Dinoflagellida, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Intracellular, Nuclear chemistry
Abstract: 31P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on 31P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ. This research was supported by the government of the Principality of Monaco. Financial support to C.G. was provided by the École Normale Supérieure and the Centre Scientifique de Monaco. peer-reviewed
Published: 2016
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34. Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression

Author: Ons, Zakraoui, Cezary, Marcinkiewicz, Zohra, Aloui, Houcemeddine, Othman, Renaud, Grépin, Meriam, Haoues, Makram, Essafi, Najet, Srairi-Abid, Ammar, Gasmi, Habib, Karoui, Gilles, Pagès, Khadija, Essafi-Benkhadir, Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée aux Maladies Infectieuses (LR11IPT04), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Centre Scientifique de Monaco (CSM), Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), 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), and This work was supported by the Tunisian Ministry of Higher Education and Scientific Research, the Institut Pasteur International Network (RIIP) and the University of Nice Sophia Antipolis, the French National Institute of Cancer (INCA) and the French Association for cancer research (ARC).
Subjects: Models, Molecular, Vascular Endothelial Growth Factor A, MESH: Vascular Endothelial Growth Factor A/genetics, MESH: Neovascularization, Pathologic/drug therapy, MESH: Colonic Neoplasms/drug therapy, MESH: Colonic Neoplasms/pathology, Apoptosis, MESH: MAP Kinase Signaling System/drug effects, MESH: Cell Proliferation/drug effects, Lebein, MESH: Colon/drug effects, MESH: Animals, MESH: Colon/metabolism, Neovascularization, Pathologic, MESH: Antineoplastic Agents/pharmacology, Integrin beta1, MESH: Chickens, MESH: Neovascularization, Pathologic/genetics, disintegrin, tumor growth, colon cancer, Colonic Neoplasms, MESH: Antineoplastic Agents/therapeutic use, MESH: Models, Molecular, MESH: Apoptosis/drug effects, MESH: Cell Line, Tumor, Colon, MAP Kinase Signaling System, MESH: Vascular Endothelial Growth Factor A/metabolism, Down-Regulation, Mice, Nude, Antineoplastic Agents, MESH: Viper Venoms/therapeutic use, [SDV.CAN]Life Sciences [q-bio]/Cancer, Viper Venoms, MESH: Cell Cycle Checkpoints/drug effects, MESH: Viper Venoms/pharmacology, Cell Line, Tumor, MESH: Down-Regulation/drug effects, MESH: Mice, Nude, Animals, Humans, MESH: Integrin beta1/metabolism, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell Proliferation, cellular effectors, MESH: Humans, Cell Cycle Checkpoints, MESH: Colonic Neoplasms/metabolism, MESH: Reactive Oxygen Species/metabolism, MESH: Colonic Neoplasms/genetics, MESH: Neovascularization, Pathologic/metabolism, MESH: Neovascularization, Pathologic/pathology, MESH: Colon/pathology, Reactive Oxygen Species, Chickens, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc.
Published: 2016
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35. Metal bioconcentration in the scleractinian coral Stylophora pistillata: investigating the role of different components of the holobiont using radiotracers

Author: Emmanuel Buschiazzo, Michel Warnau, Marc Metian, François Oberhänsli, Laetitia Hédouin, Christine Ferrier-Pagès, Jean-Louis Teyssié, Marine Environment Laboratories [Monaco] (IAEA-MEL), International Atomic Energy Agency [Vienna] (IAEA), Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'excellence 'CORAIL', and Centre Scientifique de Monaco (CSM)
Subjects: Coral, [SDE.MCG]Environmental Sciences/Global Changes, Bioconcentration, Management, Monitoring, Policy and Law, Biology, Stylophora pistillata, Environment, Metal, Botany, Biomonitoring, Ecotoxicology, Animals, 14. Life underwater, General Environmental Science, geography, geography.geographical_feature_category, General Medicine, Coral reef, biology.organism_classification, Anthozoa, Pollution, Holobiont, Metals, visual_art, visual_art.visual_art_medium, Water Pollutants, Chemical, Environmental Monitoring
Abstract: International audience; Bioconcentration kinetics of five metals (Ag, Cd, Co, Mn, and Zn) were determined in the scleractinian coral Stylophora pistillata (entire symbiotic association vs. cultured symbionts), using radiotracer techniques. Among contrasting element behaviors observed in S. pistillata, the highest efficiency of concentration and retention was observed for Ag in the symbiotic association (CFss reaching 5000 and T b½ > 1 year). Predominant proportion of this metal was found associated with the skeleton whereas the other metals were mainly present in the coral tissues (including host tissues and symbionts). A 96-h exposure of cultured symbionts (isolated zooxantellae from S. pistillata) indicated that they displayed a very high potential for metal bioconcentration (higher by 1 to 3 orders of magnitude compared to the skeleton). In addition, among the five elements investigated, Ag had the highest concentration factor in the cultured symbionts. Contrasting kinetic characteristics of skeleton vs. tissues offer interesting implications for biomonitoring purposes. Indeed, the skeleton was shown to display stable metal concentrations after an exposure (long retention time) and thereby allows recording contamination event on the long term, whereas the concentrations within coral tissues rapidly increased during the exposure and dropped when non-contaminating conditions were restored, allowing information on the current (short term) contamination status. The present study confirms that the coral can be seen as a two-compartment box model for metal bioconcentration: the tissues sensus latto as a first box governing metal entrance (with a crucial role played by the symbionts) and the skeleton as a second box where metal detoxification (storage) is taking place; the first box also depurates toward the environment when non-contaminating conditions are restored.
Published: 2015
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36. Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect

Author: Petra Krznar, Sandra Pierredon, Ibtissam Marchiq, Nicola Zamboni, Jean-Claude Martinou, Jacques Pouysségur, Vincent Compan, Benoît Vanderperre, University of Geneva [Switzerland], 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), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), 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), and Centre Scientifique de Monaco (CSM)
Subjects: Bioenergetics, [SDV]Life Sciences [q-bio], Population, Oxidative phosphorylation, Biosensing Techniques, Mitochondrion, Mitochondrial Membrane Transport Proteins, Cell Line, 03 medical and health sciences, Mitochondrial membrane transport protein, Mice, 0302 clinical medicine, Single-cell analysis, immune system diseases, Pyruvic Acid, Animals, Humans, Glycolysis, education, Molecular Biology, 030304 developmental biology, 0303 health sciences, education.field_of_study, biology, Cell Biology, Fibroblasts, Embryo, Mammalian, HCT116 Cells, Warburg effect, HEK293 Cells, Biochemistry, Energy Transfer, 030220 oncology & carcinogenesis, Luminescent Measurements, biology.protein, MCF-7 Cells, Single-Cell Analysis, HeLa Cells
Abstract: International audience; The transport of pyruvate into mitochondria requires a specific carrier, the mitochondrial pyruvate carrier (MPC). The MPC represents a central node of carbon metabolism, and its activity is likely to play a key role in bioenergetics. Until now, investigation of the MPC activity has been limited. However, the recent molecular identification of the components of the carrier has allowed us to engineer a genetically encoded biosensor and to monitor the activity of the MPC in real time in a cell population or in a single cell. We report that the MPC activity is low in cancer cells, which mainly rely on glycolysis to generate ATP, a characteristic known as the Warburg effect. We show that this low activity can be reversed by increasing the concentration of cytosolic pyruvate, thus increasing oxidative phosphorylation. This biosensor represents a unique tool to investigate carbon metabolism and bioenergetics in various cell types.
Published: 2015
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37. Trophic dynamics of scleractinian corals: stable isotope evidence

Author: Pascale Tremblay, Jean-François Maguer, Christine Ferrier-Pagès, Renaud Grover, Centre Scientifique de Monaco (CSM), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, reef corals, Light, Physiology, ved/biology.organism_classification_rank.species, Stylophora pistillata, 01 natural sciences, Symbiodinium, Nutrient, Heterotrophy, Irradiance, Turbinaria reniformis, Photosynthesis, Autotrophic Processes, Carbon Isotopes, anemone aiptasia-pallida, biology, green hydra, Ecology, bleached corals, Anthozoa, nitrogen uptake, Isotopic labeling, Heterotrophic nutrition, Dinoflagellida, Autotrophy, elevated-temperatures, Nitrogen, Heterotroph, Aquatic Science, 010603 evolutionary biology, Species Specificity, Symbiosis, Botany, Animals, 14. Life underwater, Autotroph, Molecular Biology, stylophora-pistillata, Ecology, Evolution, Behavior and Systematics, particulate matter, Nitrogen Isotopes, ved/biology, 010604 marine biology & hydrobiology, ACL, carbon, Heterotrophic Processes, sea-anemone, biology.organism_classification, Carbon, Insect Science, Animal Science and Zoology, zooxanthellate coral, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: WOS:000354114900017; Reef-building corals form symbioses with dinoflagellates from the diverse genus Symbiodinium. This symbiotic association has developed adaptations to acquire and share nutrients, which are essential for its survival and growth in nutrient-poor tropical waters. The host is thus able to prey on a wide range of organic food sources (heterotrophic nutrition) whereas the symbionts acquire most of the inorganic nutrients (autotrophic nutrition). However, nutrient fluxes between the two partners remain unclear, especially concerning heterotrophically acquired carbon and nitrogen. We combined physiological measurements and pulse-chase isotopic labeling of heterotrophic carbon and nitrogen, as well as autotrophic carbon to track nutrient fluxes in two coral species, Stylophora pistillata and Turbinaria reniformis, in symbiosis with Symbiodinium clades A, and C, D respectively. We showed a rapid acquisition, exchange and a long-term retention of heterotrophic nutrients within the symbiosis, whereas autotrophic nutrients were rapidly used to meet immediate metabolic needs. In addition, there was a higher retention of heterotrophic nitrogen compared with carbon, in agreement with the idea that tropical corals are nitrogen-limited. Finally, a coupling between auto-and heterotrophy was observed in the species S. pistillata, with a higher acquisition and retention of heterotrophic nutrients under low irradiance to compensate for a 50% reduction in autotrophic nutrient acquisition and translocation. Conversely, T. reniformis conserved an equivalent heterotrophic nutrient acquisition at both light levels because this coral species did not significantly reduce its rates of gross photosynthesis and autotrophic carbon acquisition between the two irradiances. These experiments advance the current understanding of the nutrient exchanges between the two partners of a symbiotic association, providing evidence of the complexity of the host-symbiont relationship.
Published: 2015
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38. AMP-activated protein kinase is dispensable for maintaining ATP levels and for survival following inhibition of glycolysis, but promotes tumour engraftment of ras-transformed fibroblasts

Author: Joffrey Pelletier, Danièle Roux, Benoit Viollet, Nathalie Mazure, Jacques Pouysségur, Institut de Recherche sur le Cancer et le Vieillissement ( IRCAN ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Laboratoire des sciences et matériaux pour l'électronique et d'automatique ( LASMEA ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hypoxie tumorale et métabolisme, Biologie Médicale, Centre Scientifique de Monaco ( CSM ) -Centre Scientifique de Monaco ( CSM ), This research was supported by grants from the Fondation ARC, Fondation de France, the ANR, the INCA, la Ligue Nationale Contre le Cancer (JP, équipe Labellisée LNCC), METOXIA (FP7-EU programs), MRT and Canceropôle PACA., 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), Laboratoire des sciences et matériaux pour l'électronique et d'automatique (LASMEA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM)-Centre Scientifique de Monaco (CSM), Bos, Mireille, and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Monocarboxylic Acid Transporters, AMPK, Mice, Nude, Muscle Proteins, AMPK-null cells, AMP-Activated Protein Kinases, Fibroblasts, glycolysis, Immunohistochemistry, ATP, Gene Knockout Techniques, Mice, Adenosine Triphosphate, Cell Transformation, Neoplastic, Cell Line, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Heterografts, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Priority Research Paper, cancer cell
Abstract: International audience; AbstrAct Lactic acid generated by highly glycolytic tumours is exported by the MonoCarboxylate Transporters, MCT1 and MCT4, to maintain pHi and energy homeostasis. We report that MCT1 inhibition combined with Mct4 gene disruption severely reduced glycolysis and tumour growth without affecting ATP levels. Because of the key role of the 5'-AMP-activated protein kinase (AMPK) in energy homeostasis, we hypothesized that targeting glycolysis (MCT-blockade) in AMPK-null (Ampk-/-) cells should kill tumour cells from 'ATP crisis'. We show that Ampk-/-Ras-transformed mouse embryonic fibroblasts (MEFs) maintained ATP levels and viability when glycolysis was inhibited. In MCT-inhibited MEFs treated with OXPHOS inhibitors the ATP level and viability collapsed in both Ampk +/+ and Ampk-/-cells. We therefore propose that the intracellular acidification resulting from lactic acid sequestration mimicks AMPK by blocking mTORC1, a major component of an ATP consuming pathway, thereby preventing 'ATP crisis'. Finally we showed that genetic disruption of Mct4 and/or Ampk dramatically reduced tumourigenicity in a xenograft mouse model suggesting a crucial role for these two actors in establishment of tumours in a nutrient-deprived environment. These findings demonstrated that blockade of lactate transport is an efficient anti-cancer strategy that highlights the potential in targeting Mct4 in a context of impaired AMPK activity.

39. Nitrogen fixation in the mucus of Red Sea corals

Author: Christine Ferrier-Pagès, Leïla Ezzat, Maoz Fine, Renaud Grover, Jean-François Maguer, Centre Scientifique de Monaco (CSM), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and The Interuniversity Institute for marine Science in Eilat
Subjects: 0106 biological sciences, Physiology, Nitrogen, Coral, [SDV]Life Sciences [q-bio], Scleractinia, Aquatic Science, Diazotrophy, 01 natural sciences, 03 medical and health sciences, Symbiosis, Nitrogen Fixation, Botany, Animals, Seawater, 14. Life underwater, Molecular Biology, Reef, Indian Ocean, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Stable isotopes, 0303 health sciences, geography, geography.geographical_feature_category, biology, Nitrogen Isotopes, Ecology, 010604 marine biology & hydrobiology, ACL, fungi, technology, industry, and agriculture, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Anthozoa, Holobiont, Mucus, Insect Science, Nitrogen fixation, Dinoflagellida, population characteristics, Animal Science and Zoology, Diazotroph, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, geographic locations
Abstract: Scleractinian corals are essential constituents of the tropical reefs ecological diversity. They live in close association with diazotrophs (dinitrogen (N2)-fixing microbes), which can fix high rates of N2. Whether corals benefit from this extrinsic nitrogen source is still under debate. Up to now, N2 fixation rates were indirectly estimated using the acetylene reduction assay, which does not permit assessing the amount of nitrogen incorporated into the different compartments of the coral holobiont. In the present study, the 15N2 technique was applied for the first time on three Red Sea coral species. Significant 15N enrichment was measured in particles released by corals to the surrounding seawater. N2 fixation rates were species specific and as high as 1.6 - 22 ng N d-1 L-1. However, no significant enrichment was measured in the symbiotic dinoflagellates or the coral host tissues, suggesting that corals do not benefit from diazotrophic N2 fixation.
Published: 2014
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40. Transcriptome Analysis of the Scleractinian Coral Stylophora pistillata

Author: Mali Salmon-Divon, Emeline Deleury, Sarit Karako-Lampert, Oren Levy, Mark Katzenellenbogen, Sylvie Tambutté, Anthony Bertucci, Didier Zoccola, Ove Hoegh-Guldberg, Denis Allemand, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University [Israël], Centre Scientifique de Monaco (CSM), Ariel University, Australian Research Council Centre of Excellence for Coral Reef studies, James Cook University, Université de Nice Sophia-Antipolis (UNSA), University of Queensland [Brisbane], 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), Government of the Principality of Monaco, and Israeli Science Foundation [243/10]
Subjects: Cnidaria, Science, [SDV]Life Sciences [q-bio], Scleractinia, Marine Biology, Hermatypic coral, Sea anemone, Stylophora pistillata, Transcriptomes, Genome Analysis Tools, Molecular Cell Biology, Animals, Ciona intestinalis, 14. Life underwater, analyse du transcriptome, Biology, Phylogeny, WNT Signaling Cascade, corail, Gene Library, Hydrozoa, Expressed Sequence Tags, Evolutionary Biology, Expressed sequence tag, Multidisciplinary, stylophora pistillata, biology, Coral Reefs, Ecology, Gene Expression Profiling, fungi, Computational Biology, Molecular Sequence Annotation, Genomics, Comparative Genomics, Anthozoa, biology.organism_classification, Signaling Cascades, Wnt Proteins, Evolutionary biology, Bone Morphogenetic Proteins, Corals, [SDE]Environmental Sciences, Medicine, Transcriptome, Research Article, Signal Transduction
Abstract: International audience; The principal architects of coral reefs are the scleractinian corals; these species are divided in two major clades referred to as "robust'' and "complex'' corals. Although the molecular diversity of the "complex'' clade has received considerable attention, with several expressed sequence tag (EST) libraries and a complete genome sequence having been constructed, the "robust'' corals have received far less attention, despite the fact that robust corals have been prominent focal points for ecological and physiological studies. Filling this gap affords important opportunities to extend these studies and to improve our understanding of the differences between the two major clades. Here, we present an EST library from Stylophora pistillata (Esper 1797) and systematically analyze the assembled transcripts compared to putative homologs from the complete proteomes of six well-characterized metazoans: Nematostella vectensis, Hydra magnipapillata, Caenorhabditis elegans, Drosophila melanogaster, Strongylocentrotus purpuratus, Ciona intestinalis and Homo sapiens. Furthermore, comparative analyses of the Stylophora pistillata ESTs were performed against several Cnidaria from the Scleractinia, Actiniaria and Hydrozoa, as well as against other stony corals separately. Functional characterization of S. pistillata transcripts into KOG/COG categories and further description of Wnt and bone morphogenetic protein (BMP) signaling pathways showed that the assembled EST library provides sufficient data and coverage. These features of this new library suggest considerable opportunities for extending our understanding of the molecular and physiological behavior of "robust'' corals.
Published: 2014
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41. Microstructural evolution and nanoscale crystallography in scleractinian coral spherulites

Author: Aurelie Moya, Renée van de Locht, Tim Rixen, Andreas Verch, Martin Saunders, Delphine Dissard, Roland Kröger, University of York [York, UK], School of Earth and Environment (UWA), The University of Western Australia (UWA), ARC Centre of Excellence for Coral Reef Studies (CoralCoE), James Cook University (JCU), Leibniz Centre for Tropical Marine Research (ZMT), Centre Scientifique de Monaco (CSM), and Centre Scientifique de Monaco
Subjects: Acicular, Materials science, Crystallography, Aragonite, [PHYS.PHYS.PHYS-GEO-PH]Physics [physics]/Physics [physics]/Geophysics [physics.geo-ph], engineering.material, Microstructure, Anthozoa, Focused ion beam, Evolution, Molecular, chemistry.chemical_compound, Calcium carbonate, chemistry, Microscopy, Electron, Transmission, Structural Biology, Transmission electron microscopy, engineering, Animals, Nanoparticles, Nanotechnology, Mesocrystal, ComputingMilieux_MISCELLANEOUS, Biomineralization
Abstract: One of the most important aspects in the research on reef-building corals is the process by which corals accrete biogenic calcium carbonate. This process leads to the formation of a mineral/organic composite and it is believed that the development of the nano- and microstructure of the mineral phase is highly sensitive to the growth conditions. Transmission electron microscopy (TEM) analysis of large-scale (10 × 30 μm) focused ion beam (FIB) prepared lamellae was performed on adult and juvenile scleractinian coral skeleton specimens. This allowed for the investigation of the nano and microstructure and the crystallographic orientation of the aragonite mineral. We found the following microstructural evolution in the adult Porites lobata specimens: randomly oriented nanocrystals with high porosity, partly aligned nanocrystals with high porosity and areas of dense acicular crystals of several micrometers extension, the latter two areas are aligned close to the [0 0 1] direction (Pmcn space group). To the best of our knowledge, for the first time the observed microstructure could be directly correlated with the dark/bright bands characteristic of the diurnal growth cycle. We hypothesize that this mineral structure sequence and alignment in the adult specimen is linked to the photosynthetic diurnal cycle of the zooxanthellea regulating the oxygen levels and organic molecule transport to the calcifying medium. These observations reveal a strong control of crystal morphology by the organism and the correlation of the accretion process. No indication for a self-assembly of nanocrystalline units, i.e., a mesocrystal structure, on the micrometer scale could be found.
Published: 2013
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42. Genes Related to Ion-Transport and Energy Production Are Upregulated in Response to CO2-Driven pH Decrease in Corals: New Insights from Transcriptome Analysis

Author: Jeremie Vidal-Dupiol, Eric Tambutté, Christoph Grunau, Sylvie Tambutté, Didier Zoccola, Nolwenn M. Dheilly, Kristina M. Smith, Céline Cosseau, Denis Allemand, Michael Freitag, Ecologie et évolution des interactions [2011-2014] (2EI), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Centre Scientifique de Monaco, Center for Genome Research and Biocomputing, and Oregon State University (OSU)
Subjects: 0106 biological sciences, Biomineralization, Anatomy and Physiology, Coral, Gene Expression, Stylophora pistillata, 01 natural sciences, Transcriptomes, Transcriptome, Acropora millepora, Molecular Cell Biology, 0303 health sciences, Multidisciplinary, geography.geographical_feature_category, biology, Ecology, Reverse Transcriptase Polymerase Chain Reaction, Ocean acidification, Coral reef, Genomics, Hydrogen-Ion Concentration, Anthozoa, Cell biology, Functional Genomics, Up-Regulation, Medicine, Research Article, Science, Marine Biology, Pocillopora damicornis, 010603 evolutionary biology, Molecular Genetics, 03 medical and health sciences, Genome Analysis Tools, Animals, Seawater, 14. Life underwater, Biology, 030304 developmental biology, geography, Ion Transport, Sequence Analysis, RNA, Gene Expression Profiling, Computational Biology, Reproducibility of Results, Molecular Sequence Annotation, Carbon Dioxide, biology.organism_classification, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Physiological Processes, Genome Expression Analysis, Energy Metabolism
Abstract: International audience; Since the preindustrial era, the average surface ocean pH has declined by 0.1 pH units and is predicted to decline by an additional 0.3 units by the year 2100. Although subtle, this decreasing pH has profound effects on the seawater saturation state of carbonate minerals and is thus predicted to impact on calcifying organisms. Among these are the scleractinian corals, which are the main builders of tropical coral reefs. Several recent studies have evaluated the physiological impact of low pH, particularly in relation to coral growth and calcification. However, very few studies have focused on the impact of low pH at the global molecular level. In this context we investigated global transcriptomic modifications in a scleractinian coral (Pocillopora damicornis) exposed to pH 7.4 compared to pH 8.1during a 3-week period. The RNAseq approach shows that 16% of our transcriptome was affected by the treatment with 6% of upregulations and 10% of downregulations. A more detailed analysis suggests that the downregulations are less coordinated than the upregulations and allowed the identification of several biological functions of interest. In order to better understand the links between these functions and the pH, transcript abundance of 48 candidate genes was quantified by q-RT-PCR (corals exposed at pH 7.2 and 7.8 for 3 weeks). The combined results of these two approaches suggest that pH$7.4 induces an upregulation of genes coding for proteins involved in calcium and carbonate transport, conversion of CO2 into HCO3 2 and organic matrix that may sustain calcification. Concomitantly, genes coding for heterotrophic and autotrophic related proteins are upregulated. This can reflect that low pH may increase the coral energy requirements, leading to an increase of energetic metabolism with the mobilization of energy reserves. In addition, the uncoordinated downregulations measured can reflect a general trade-off mechanism that may enable energy reallocation.
Published: 2013

43. Carbonic anhydrases in anthozoan corals-A review

Author: Claudiu T. Supuran, Sylvie Tambutté, Aurelie Moya, Anthony Bertucci, Denis Allemand, Didier Zoccola, Australian Research Council Centre of Excellence for Coral Reef studies, James Cook University (JCU), Centre Scientifique de Monaco (CSM), Université de Nice Sophia-Antipolis (UNSA), Centre Scientifique de Monaco, Laboratoire d'océanographie de Villefranche (LOV), 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), NEUROFARBA Department [Firenze, Italy], Università degli Studi di Firenze = University of Florence (UniFI), James Cook University, 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), and Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)
Subjects: 0106 biological sciences, Coral, Clinical Biochemistry, Pharmaceutical Science, 010603 evolutionary biology, 01 natural sciences, Biochemistry, Calcium Carbonate, 03 medical and health sciences, chemistry.chemical_compound, Symbiosis, Anthozoa, Drug Discovery, Botany, Animals, Humans, Ecosystem, 14. Life underwater, Photosynthesis, Carbonic Anhydrase Inhibitors, Molecular Biology, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, Phylogeny, 030304 developmental biology, Carbonic Anhydrases, 0303 health sciences, geography, geography.geographical_feature_category, biology, Ecology, Organic Chemistry, Coral reef, 15. Life on land, biology.organism_classification, Mitochondria, Isoenzymes, Calcium carbonate, chemistry, Zooxanthellae, Molecular Medicine, Biomineralization
Abstract: Coral reefs are among the most biologically diverse and economically important ecosystems on the planet. The deposition of massive calcium carbonate skeletons (biomineralization or calcification) by scleractinian corals forms the coral reef framework/architecture that serves as habitat for a large diversity of organisms. This process would not be possible without the intimate symbiosis between corals and photosynthetic dinoflagellates, commonly called zooxanthellae. Carbonic anhydrases play major roles in those two essential processes of coral's physiology: they are involved in the carbon supply for calcium carbonate precipitation as well as in carbon-concentrating mechanisms for symbiont photosynthesis. Here, we review the current understanding of diversity and function of carbonic anhydrases in corals and discuss the perspective of theses enzymes as a key to understanding impacts of environmental changes on coral reefs. (C) 2012 Elsevier Ltd. All rights reserved.
Published: 2012
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44. Autotrophic carbon budget in coral tissue: a new 13C-based model of photosynthate translocation

Author: Louis Legendre, Christine Ferrier-Pagès, Pascale Tremblay, Renaud Grover, Jean-François Maguer, Centre Scientifique de Monaco (CSM), CSM, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'océanographie de Villefranche (LOV), 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), Centre Scientifique de Monaco, Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Natural Sciences and Engineering Research Council of Canada ES D3-378797-2009, Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and 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)
Subjects: 0106 biological sciences, Time Factors, Physiology, C-13, Coral, chemistry.chemical_element, Aquatic Science, Biology, Stylophora pistillata, 01 natural sciences, Models, Biological, 03 medical and health sciences, Botany, Dissolved organic carbon, Animals, 14. Life underwater, Autotroph, Photosynthesis, 13C, Molecular Biology, coral, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Total organic carbon, 0303 health sciences, Analysis of Variance, Autotrophic Processes, Carbon Isotopes, 010604 marine biology & hydrobiology, Terrestrial biological carbon cycle, fungi, Biological Transport, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Anthozoa, Carbon, chemistry, Isotopes of carbon, photosynthate translocation, Insect Science, autotrophy, [SDE]Environmental Sciences, Animal Science and Zoology
Abstract: SUMMARY Corals live in symbiosis with dinoflagellates of the genus Symbiodinum. These dinoflagellates translocate a large part of the photosynthetically fixed carbon to the host, which in turn uses it for its own needs. Assessing the carbon budget in coral tissue is a central question in reef studies that still vexes ecophysiologists. The amount of carbon fixed by the symbiotic association can be determined by measuring the rate of photosynthesis, but the amount of carbon translocated by the symbionts to the host and the fate of this carbon are more difficult to assess. In the present study, we propose a novel approach to calculate the budget of autotrophic carbon in the tissue of scleractinian corals, based on a new model and measurements made with the stable isotope 13C. Colonies of the scleractinian coral Stylophora pistillata were incubated in H13CO –3-enriched seawater, after which the fate of 13C was followed in the symbionts, the coral tissue and the released particulate organic carbon (i.e. mucus). Results obtained showed that after 15 min, ca. 60% of the carbon fixed was already translocated to the host, and after 48 h, this value reached 78%. However, ca. 48% of the photosynthetically fixed carbon was respired by the symbiotic association, and 28% was released as dissolved organic carbon. This is different from other coral species, where
Published: 2012
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45. Controlling effects of irradiance and heterotrophy on carbon translocation in the temperate coral Cladocora caespitosa

Author: Christine Ferrier-Pagès, Cécile Rottier, Pascale Tremblay, Renaud Grover, Jean-François Maguer, Louis Legendre, Centre Scientifique de Monaco (CSM), CSM, BIOSENSIB, CSM-CNRS, Centre Scientifique de Monaco, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'océanographie de Villefranche (LOV), 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and 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)
Subjects: 0106 biological sciences, Light, Ecophysiology, Coral, Irradiance, Heterotroph, Marine and Aquatic Sciences, lcsh:Medicine, chemistry.chemical_element, Marine Biology, Plant Science, Oceanography, Photosynthesis, 010603 evolutionary biology, 01 natural sciences, Botany, Dissolved organic carbon, Animals, 14. Life underwater, Autotroph, lcsh:Science, Biology, Multidisciplinary, Ecology, Coral Reefs, Plant Biochemistry, Chemistry, 010604 marine biology & hydrobiology, Biological Oceanography, lcsh:R, Carbon fixation, fungi, Marine Ecology, Biological Transport, biochemical phenomena, metabolism, and nutrition, Anthozoa, Carbon, Corals, [SDE]Environmental Sciences, Earth Sciences, lcsh:Q, Research Article
Abstract: International audience; Temperate symbiotic corals, such as the Mediterranean species Cladocora caespitosa, live in seasonally changing environments, where irradiance can be ten times higher in summer than winter. These corals shift from autotrophy in summer to heterotrophy in winter in response to light limitation of the symbiont's photosynthesis. In this study, we determined the autotrophic carbon budget under different conditions of irradiance (20 and 120 µmol photons m(-2) s(-1)) and feeding (fed three times a week with Artemia salina nauplii, and unfed). Corals were incubated in H(13)CO(3) (-)-enriched seawater, and the fate of (13)C was followed in the symbionts and the host tissue. The total amount of carbon fixed by photosynthesis and translocated was significantly higher at high than low irradiance (ca. 13 versus 2.5-4.5 µg cm(-2) h(-1)), because the rates of photosynthesis and carbon fixation were also higher. However, the percent of carbon translocation was similar under the two irradiances, and reached more than 70% of the total fixed carbon. Host feeding induced a decrease in the percentage of carbon translocated under low irradiance (from 70 to 53%), and also a decrease in the rates of carbon translocation per symbiont cell under both irradiances. The fate of autotrophic and heterotrophic carbon differed according to irradiance. At low irradiance, autotrophic carbon was mostly respired by the host and the symbionts, and heterotrophic feeding led to an increase in host biomass. Under high irradiance, autotrophic carbon was both respired and released as particulate and dissolved organic carbon, and heterotrophic feeding led to an increase in host biomass and symbiont concentration. Overall, the maintenance of high symbiont concentration and high percentage of carbon translocation under low irradiance allow this coral species to optimize its autotrophic carbon acquisition, when irradiance conditions are not favourable to photosynthesis.
Published: 2012
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46. Glycan profiling of gel forming mucus layer from the scleractinian symbiotic coral oculina arbuscula

Author: Yann Guérardel, Bernadette Coddeville, Christine Ferrier-Pagès, Emmanuel Maes, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Centre Scientifique de Monaco, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Glycan, Polymers and Plastics, Glycoconjugate, Coral, Molecular Sequence Data, Bioengineering, 01 natural sciences, Mass Spectrometry, Microbiology, Biomaterials, 03 medical and health sciences, Symbiosis, Polysaccharides, Anthozoa, Materials Chemistry, Animals, 14. Life underwater, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Ecosystem, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Bacteria, 010604 marine biology & hydrobiology, Mucin, Mucins, biology.organism_classification, Mucus, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Biochemistry, chemistry, Carbohydrate Sequence, biology.protein, Gels, Glycoconjugates
Abstract: International audience; The gel forming mucus layer surrounding scleractinian corals play fundamental functions in the maintenance of a favorable microenvironment required for the survival of these organisms. In particular, it harbors a rich partially species-specific symbiotic community through yet poorly understood molecular interactions. However, removal or contamination of this community by exogenous bacteria is closely linked to the worldwide bleaching events that are presently devastating coral colonies. The present study investigates the structure of major high molecular weight glycoconjugates that are responsible for both rheological properties of mucus and sugar-protein interactions with microbial communities. We demonstrated that it is composed by two distinct types of sulfated macromolecules: mucin type glycoproteins densely substituted by short unusual O-linked glycans and repetitive polysaccharides.
Published: 2011
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47. Innate immune responses of a scleractinian coral to Vibriosis

Author: Guillaume Mitta, Pierre-Eric Sautière, David Duval, Laurent Fouré, Sylvie Tambutté, Jeremie Vidal-Dupiol, Mehdi Adjeroud, Eric Tambutté, Delphine Destoumieux-Garzón, Anne-Leila Meistertzheim, Ophélie Ladrière, Ecologie et évolution des interactions [2011-2014] (2EI), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Unité d'Ecologie Marine, Université de Liège, Ecosystèmes lagunaires : organisation biologique et fonctionnement (ECOLAG), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), Neuroimmunologie des annélides (NA), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), and Biocomplexité des écosystèmes coralliens de l'Indo-Pacifique (CoReUS2)
Subjects: 0106 biological sciences, Cnidaria, Coral, Antimicrobial peptides, Bacterial Toxins, Molecular Sequence Data, Immunology, Pocillopora damicornis, 010603 evolutionary biology, 01 natural sciences, Biochemistry, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, 03 medical and health sciences, Anthozoa, Animals, 14. Life underwater, Amino Acid Sequence, Disulfides, Molecular Biology, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, 030304 developmental biology, Vibrio, 0303 health sciences, Innate immune system, biology, Base Sequence, Vibrio coralliilyticus, Cell Biology, biology.organism_classification, Immunity, Innate, Protein Transport, Gene Expression Regulation, 13. Climate action, Antimicrobial Cationic Peptides
Abstract: Scleractinian corals are the most basal eumetazoan taxon and provide the biological and physical framework for coral reefs, which are among the most diverse of all ecosystems. Over the past three decades and coincident with climate change, these phototrophic symbiotic organisms have been subject to increasingly frequent and severe diseases, which are now geographically widespread and a major threat to these ecosystems. Although coral immunity has been the subject of increasing study, the available information remains fragmentary, especially with respect to coral antimicrobial responses. In this study, we characterized damicornin from Pocillopora damicornis, the first scleractinian antimicrobial peptide (AMP) to be reported. We found that its precursor has a segmented organization comprising a signal peptide, an acidic proregion, and the C-terminal AMP. The 40-residue AMP is cationic, C-terminally amidated, and characterized by the presence of six cysteine molecules joined by three intramolecular disulfide bridges. Its cysteine array is common to another AMP and toxins from cnidarians; this suggests a common ancestor, as has been proposed for AMPs and toxins from arthropods. Damicornin was active in vitro against Gram-positive bacteria and the fungus Fusarium oxysporum. Damicornin expression was studied using a combination of immunohistochemistry, reverse phase HPLC, and quantitative RT-PCR. Our data show that damicornin is constitutively transcribed in ectodermal granular cells, where it is stored, and further released in response to nonpathogenic immune challenge. Damicornin gene expression was repressed by the coral pathogen Vibrio coralliilyticus. This is the first evidence of AMP gene repression in a host-Vibrio interaction.
Published: 2011
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48. Coral uptake of inorganic phosphorus and nitrogen negatively affected by simultaneous changes in temperature and pH

Author: Claire Godinot, Renaud Grover, Fanny Houlbrèque, Christine Ferrier-Pagès, Centre Scientifique de Monaco (CSM), Centre Scientifique de Monaco, Biocomplexité des écosystèmes coralliens de l'Indo-Pacifique (CoReUS2), and Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])
Subjects: 0106 biological sciences, 010504 meteorology & atmospheric sciences, Nitrogen, Ecophysiology, Marine and Aquatic Sciences, chemistry.chemical_element, lcsh:Medicine, Marine Biology, Photosynthetic efficiency, Biology, 01 natural sciences, Phosphorus metabolism, chemistry.chemical_compound, Nitrate, Global Change Ecology, Botany, Animals, Ammonium, 14. Life underwater, Photosynthesis, lcsh:Science, 0105 earth and related environmental sciences, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Multidisciplinary, Ecology, Coral Reefs, 010604 marine biology & hydrobiology, Phosphorus, lcsh:R, Temperature, Marine Ecology, Ocean acidification, Hydrogen-Ion Concentration, Biogeochemistry, Anthozoa, Phosphate, chemistry, 13. Climate action, Environmental chemistry, Carbon dioxide, Earth Sciences, lcsh:Q, Coastal Ecology, Research Article
Abstract: International audience; The effects of ocean acidification and elevated seawater temperature on coral calcification and photosynthesis have been extensively investigated over the last two decades, whereas they are still unknown on nutrient uptake, despite their importance for coral energetics. We therefore studied the separate and combined impacts of increases in temperature and pCO(2) on phosphate, ammonium, and nitrate uptake rates by the scleractinian coral S. pistillata. Three experiments were performed, during 10 days i) at three pHT conditions (8.1, 7.8, and 7.5) and normal temperature (26 degrees C), ii) at three temperature conditions (26 degrees, 29 degrees C, and 33 degrees C) and normal pH(T) (8.1), and iii) at three pH(T) conditions (8.1, 7.8, and 7.5) and elevated temperature (33 degrees C). After 10 days of incubation, corals had not bleached, as protein, chlorophyll, and zooxanthellae contents were the same in all treatments. However, photosynthetic rates significantly decreased at 33 degrees C, and were further reduced for the pH(T) 7.5. The photosynthetic efficiency of PSII was only decreased by elevated temperature. Nutrient uptake rates were not affected by a change in pH alone. Conversely, elevated temperature (33 degrees C) alone induced an increase in phosphate uptake but a severe decrease in nitrate and ammonium uptake rates, even leading to a release of nitrogen into seawater. Combination of high temperature (33 degrees C) and low pH(T) (7.5) resulted in a significant decrease in phosphate and nitrate uptake rates compared to control corals (26 degrees C, pH(T) = 8.1). These results indicate that both inorganic nitrogen and phosphorus metabolism may be negatively affected by the cumulative effects of ocean warming and acidification.
Published: 2011
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49. Specific expression of BMP2/4 ortholog in biomineralizing tissues of corals and action on mouse BMP receptor

Author: Denis Allemand, Didier Zoccola, Aurelie Moya, Guillaume E. Beranger, Eric Tambutté, Sylvie Tambutté, Georges F. Carle, Centre Scientifique de Monaco (CSM), Centre Scientifique de Monaco, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), 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), and CSM
Subjects: Cnidaria, animal structures, Coral, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Bone Morphogenetic Protein 4, Bone Morphogenetic Protein 2, MESH: Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Bone morphogenetic protein, MESH: Bone Morphogenetic Protein Receptors, Applied Microbiology and Biotechnology, Bone morphogenetic protein 2, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Animals, Humans, MESH: Protein Binding, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 14. Life underwater, Receptor, MESH: Mice, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, MESH: Humans, MESH: Molecular Sequence Data, biology, fungi, technology, industry, and agriculture, Anatomy, Bone Morphogenetic Protein Receptors, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Anthozoa, MESH: Gene Expression Regulation, Cell biology, MESH: Cell Line, Gene Expression Regulation, MESH: Anthozoa, embryonic structures, C2C12, Sequence Alignment, 030217 neurology & neurosurgery, Biomineralization, Protein Binding
Abstract: International audience; Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta superfamily, and have been identified by their ability to induce bone formation in vertebrates. The biomineral-forming process, called biomineralization, is a widespread process, present in all kingdoms of living organisms and among which stony corals are one of the major groups of calcifying animals. Here, we report the presence of a BMP2/4 ortholog in eight species of adult corals. The synthesis of such a protein by the calcifying epithelium of corals suggests that coral BMP2/4 plays a role in skeletogenesis, making BMP the first common protein involved in biomineralization among Eumetazoans. In addition we show that recombinant coral BMP2/4 is able to inhibit human BMP2-induced osteoblastic differentiation in mesenchymal C2C12 cells. We suggest that this inhibition results from a competition between coral BMP2/4 and human BMP2, indicating conservation of binding affinity of BMP and its receptor during evolution from corals to vertebrates. Further studies are needed to understand interactions between coral BMP2/4 and its receptors, and, thus, the action of BMP2/4 in adult corals.
Published: 2009
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50. Uptake of dissolved free amino acids by the scleractinian coral Stylophora pistillata

Author: Denis Allemand, Christine Ferrier-Pagès, Renaud Grover, Jean-François Maguer, Centre Scientifique de Monaco (CSM), CSM, Laboratoire de chimie marine, and Centre Scientifique de Monaco
Subjects: 0106 biological sciences, Physiology, Nitrogen, chemistry.chemical_element, Biological Transport, Active, Uptake, Aquatic Science, Biology, Stylophora pistillata, 01 natural sciences, Models, Biological, 03 medical and health sciences, Ammonia, chemistry.chemical_compound, Isotopic enrichment, Nitrate, Botany, Animals, Amino Acids, Molecular Biology, Nitrogen cycle, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Nitrogen Isotopes, 010604 marine biology & hydrobiology, biology.organism_classification, Anthozoa, Isotopes of nitrogen, Kinetics, Spectrometry, Fluorescence, chemistry, Insect Science, Zooxanthellae, Environmental chemistry, [SDE]Environmental Sciences, Urea, Dinoflagellida, Animal Science and Zoology, Dissolved free amino acid, Coral
Abstract: SUMMARY This study was designed to assess the importance of dissolved free amino acids (DFAA) as a nitrogen source for the scleractinian coral Stylophora pistillata. For this purpose, experiments were performed using 15N-enriched DFAAs, and %15N enrichment was measured both in animal tissue and zooxanthellae at different DFAA concentrations,incubation time and light levels. As previously observed for urea, which is another source of organic nitrogen, DFAA uptake exhibited a biphasic mode consisting of an active carrier-mediated transport for concentrations below 3μmol l–1 and a linear uptake for higher concentrations. The value of the carrier affinity (Km=1.23 μmol l–1 DFAA) indicated good adaptation of the corals to the low levels of DFAA concentrations measured in most oligotrophic waters. DFAA uptake was also correlated with light. The DFAA contribution to the nitrogen requirements for tissue growth was compared to the contribution of ammonia,nitrate and urea, for which uptake was also measured in S. pistillata. Inorganic sources (NH4+ and NO3–) contributed 75% of the daily nitrogen needs against 24% for organic sources. Taken altogether, dissolved organic and inorganic nitrogen can supply almost 100% of the nitrogen needs for tissue growth.
Published: 2008
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