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44 results on '"SDV:BBM"'

1. Assessing Global DNA Methylation Changes Associated with Plasticity in Seven Highly Inbred Lines of Snapdragon Plants (Antirrhinum majus)

Author: Mathieu Latutrie, Mathilde Mousset, Stéphane Maury, Benoit Pujol, Alain Delaunay, Sara Marin, Delphine Gourcilleau, Evolution et Diversité Biologique (EDB), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, 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 de Biologie des Ligneux et des Grandes Cultures (LBLGC), Institut National de la Recherche Agronomique (INRA)-Université d'Orléans (UO), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE)
Subjects: 0106 biological sciences, 0301 basic medicine, [SDV]Life Sciences [q-bio], 01 natural sciences, phenotypic plasticity, Epigenesis, Genetic, Antirrhinum majus, Morphogenesis, Antirrhinum, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Morphogenèse, Genetics, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Vegetal Biology, DNA methylation, snapdragon, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, Adaptation, Physiological, Botanique, Phenotype, Botanics, lcsh:QH426-470, stem elongation, shade avoidance, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, DNA sequencing, Article, 03 medical and health sciences, Shade avoidance, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], SDV:BBM, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epigenetics, Gene, Phenotypic plasticity, [SDV.GEN]Life Sciences [q-bio]/Genetics, fungi, Genetic Variation, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, SDV:BBM:GTP, biology.organism_classification, lcsh:Genetics, 030104 developmental biology, DNA demethylation, Biologie végétale, 010606 plant biology & botany
Abstract: International audience; Genetic and epigenetic variations are commonly known to underlie phenotypic plastic responses to environmental cues. however, the role of epigenetic variation in plastic responses harboring ecological significance in nature remains to be assessed. The shade avoidance response (SAR) of plants is one of the most prevalent examples of phenotypic plasticity. It is a phenotypic syndrome including stem elongation and multiple other traits. Its ecological significance is widely acknowledged, and it can be adaptive in the presence of competition for light. Underlying genes and pathways were identified, but evidence for its epigenetic basis remains scarce. We used a proven and accessible approach at the population level and compared global DNA methylation between plants exposed to regular light and three different magnitudes of shade in seven highlyinbred lines of snapdragon plants (Antirrhinum majus) grown in a greenhouse. Our results brought evidence of a strong SAR syndrome for which magnitude did not vary between lines. They also brought evidence that its magnitude was not associated with the global DNA methylation percentage for five of the six traits under study. The magnitude of stem elongation was significantly associated with global DNA demethylation. We discuss the limits of this approach and why caution must be taken with such results. In-depth approaches at the DNA sequence level will be necessary to better understand the molecular basis of the SAR syndrome
Published: 2019
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2. Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions

Author: Vu Manh, Thien-Phong, Bertho, Nicolas, Hosmalin, Anne, Schwartz-Cornil, Isabelle, Dalod, Marc, Centre d'Immunologie de Marseille - Luminy (CIML), Université de la Méditerranée - Aix-Marseille 2 - Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut Cochin, Université Paris Descartes - Paris 5 (UPD5) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), CHU Cochin [APHP], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), 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), INSERM, CNRS, INRA, CNRS-AP-HP collaboration, Aix-Marseille University, Universite Paris Descartes, Universite Paris Diderot, ANRS, Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0073-02, ANR-11-ISV3-0001], 'Integrative Biology of Emerging Infectious Diseases' Labex (ANR-10-LABX-62-IBEID), DCBIOL Labex [ANR-11-LABEX-0043, ANR-10-IDEX0001-02 PSL*], A*MIDEX project - French Government's 'Investissements d'Avenir' program [ANR-11-IDEX0001-02], European Project: 281225,EC:FP7:ERC,ERC-2011-StG_20101109,SYSTEMSDENDRITIC(2012), Bos, Mireille, Harnessing systems immunology to unravel dendritic cell subset biology - SYSTEMSDENDRITIC - - EC:FP7:ERC2012-02-01 - 2017-01-31 - 281225 - VALID, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: lcsh:Immunologic diseases. Allergy, pig, ANTIGEN CROSS-P, TRANSCRIPTION F, TRANSCRIPTION FACTOR ZDC, STEADY-STATE, sheep, [SDV.IMM] Life Sciences [q-bio]/Immunology, chicken, Immunology, LANGERHANS CELL, HUMAN CD1C(+), Review, [SDV.GEN] Life Sciences [q-bio]/Genetics, comparative genomics, C-TYPE LECTIN, SDV:BBM, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, ANTIGEN CROSS-PRESENTATION, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, human, IN-VIVO, mouse, comparative gen, Vaccination, LANGERHANS CELLS, Dendritic Cells, mononuclear pha, HUMAN BLOOD, [SDV] Life Sciences [q-bio], GENE-EXPRESSION, GENE-EXPRESSION PROFILES, non-human primates, mononuclear phagocytes, T-CELLS, non-human prima, lcsh:RC581-607
Abstract: International audience; Dendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks, and com-plementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization, and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation, and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes, and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types, organs, and species.
Published: 2015
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3. Human Immunodeficiency Virus Protease Inhibitors Accumulate into Cultured Human Adipocytes and Alter Expression of Adipocytokines

Author: CÃ©cile Vernochet, StÃ©phane Azoulay, Christian Dani, Roger Guedj, Hubert Vidal, GÃ©rard Ailhaud, Daniele Duval, FranÃ§oise Cottrez, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Laboratoire de Chimie des Molécules Bioactives et des Arômes (LCMBA), 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), Interactions cellulaires en immunologie et immunopathologie, Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Oillaux, Genevieve
Subjects: Adipocytes, Cell Differentiation, Chromatography, High Pressure Liquid, Cytokines, Enzyme-Linked Immunosorbent Assay, HIV Protease Inhibitors, Humans, Insulin Resistance, Reverse Transcriptase Inhibitors, Spectrophotometry, Ultraviolet, Adipose tissue, Biochemistry, chemistry.chemical_compound, MESH: Spectrophotometry, Ultraviolet, Adipocyte, HIV Protease Inhibitor, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Chromatography, High Pressure Liquid, MESH: Cytokines, 0303 health sciences, Biologie du développement, MESH: Enzyme-Linked Immunosorbent Assay, virus diseases, Lopinavir, Development Biology, 3. Good health, MESH: Insulin Resistance, Adipogenesis, medicine.drug, MESH: Cell Differentiation, medicine.medical_specialty, Biology, 03 medical and health sciences, Amprenavir, Internal medicine, [SDV.BDD] Life Sciences [q-bio]/Development Biology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Chromatography, High Pressure Liquid, Molecular Biology, MESH: Adipocytes, MESH: HIV Protease Inhibitors, 030304 developmental biology, MESH: Humans, 030306 microbiology, Cell Biology, Endocrinology, chemistry, Spectrophotometry, Ultraviolet, Ritonavir, MESH: Reverse Transcriptase Inhibitors, Saquinavir
Abstract: International audience; Lipodystrophic syndrome is a major side effect of highly active antiviral therapy. Fat tissue redistribution is associated with changes in adipocyte gene expression and in circulating levels of adipocytokines involved in the development of insulin resistance. However, the evidence that HIV drugs accumulate into human adipocytes and have a direct effect on the expression of adipocyte-specific genes is still lacking. To address these questions, we used adipocytes derived from adult stem (hMADS) cells isolated from human adipose tissue. We showed by ELISA that two inhibitors of the HIV protease, lopinavir and ritonavir, accumulated at similar levels during the development of hMADS cells in adipocytes, whereas a non-nucleoside reverse transcriptase inhibitor, the nevirapine, accumulated at lower levels. Two fluorescent protease inhibitors then have been generated to investigate their subcellular localization. The data showed that HIV drugs accumulated into adipocytes and displayed various effects on hMADS cell-derived adipocytes. Indinavir, amprenavir, and nevirapine did not alter differentiation of precursor cells. In contrast, lopinavir, saquinavir, and ritonavir inhibited the development of preadipocytes into adipocytes. In adipocytes, amprenavir increased leptin expression and ritonavir was able to up-regulate tumor necrosis factor-alpha, interleukin 6, and leptin expression and down-regulate the expression of peroxisome proliferator-activated receptor gamma and adiponectin. Intracellular accumulation and localization of HIV drugs into human adipocytes strongly suggest that adipose tissues store these drugs. Because ritonavir can alter the expression of insulin resistance-related cytokines in human adipocytes in a way parallel to the situation observed in vivo upon treatment of HIV-infected patients, we propose that protease inhibitors participate in insulin resistance through a direct effect on adipocytes.
Published: 2005
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4. Rôle des Cytochromes P450 dans la perception sensorielle et le métabolisme de la caféine chez Drosophila melanogaster

Author: Coelho, Alexandra, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université de Bourgogne, Jean-Marie Heydel, Stéphane Fraichard, Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )
Subjects: Métyrapone, Cytochrome P450, Chimioprotection, Metabolism, Caffeine, Taste perception, Drosophila, Cytochromes P450, Caféine, Evènement péri-récepteur, Gustation, Récepteurs gustatifs, Drosophile, Métabolisme, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: Les insectes ont développé un système chimiosensoriel gustatif leur permettant de discriminer les stimuli sensoriels indispensables à leur survie et à leur reproduction. Afin d’être efficace, le système gustatif doit être sensible et permettre une élimination rapide des molécules sensorielles afin d’éviter la saturation des récepteurs et ainsi assurer la détection et l’intégration des signaux chimiosensoriels. Présentes dans l’espace péri-récepteur, les enzymes du métabolisme des xénobiotiques (EMX), impliquées principalement dans la détoxication des organismes, pourraient avoir un rôle central dans la modification et/ou l’arrêt du signal sensoriel en catalysant la biotransformation de ces molécules et en favorisant leur élimination.Afin d’analyser l’implication des EMX dans les processus chimiosensoriels, nous avons centré notre étude sur le rôle potentiel des Cytochromes P450 (CYP), dans la perception et le métabolisme de la caféine chez Drosophila melanogaster. Nous avons identifié plusieurs CYP dont l’expression est fortement modulée dans les organes sensoriels et dans le corps par la caféine. L’inhibition ciblée de l’expression de certains CYP dans les neurones sensoriels provoque une perturbation de la perception de la caféine, mettant ainsi en évidence le rôle crucial de ces enzymes dans les mécanismes chimiosensoriels. En parallèle, nous avons caractérisé le métabolisme de la caféine chez la drosophile puis, nous avons mis en évidence l’implication directe de CYP6d5 dans la dégradation de la caféine en théobromine.L’ensemble de ces travaux montre pour la première fois, l’implication directe des cytochromes P450 dans les mécanismes de perception sensorielle et dans le métabolisme de la caféine chez la drosophile., Insects have developed a gustatory system, allowing them to detect sensory molecules essential to their survival and their reproduction. In order to be efficient, the gustatory system must be sensitive, allowing a rapid elimination of sensory molecules in order to avoid the receptor saturation and insuring the detection and the integration of chemosensory signals.Located in the peri-receptor environment, xenobiotic metabolizing enzymes (EMX), mainly implicated in detoxification, could have a crucial role in the modulation of the sensory signal by catalyzing the biotransformation of sensory molecules and promoting their elimination.To analyze the involvement of XME in chemosensory processes, we focused our project on the putative role of Cytochromes P450 (CYP) in caffeine sensory perception and metabolism in Drosophila melanogaster. We identified several CYP, which the expression is strongly modulated in sensory organs and in the body by caffeine. The specific-targeted silencing of some CYP expression in sensory neurons leads to an alteration of caffeine perception, revealing the crucial role of these enzymes in chemoperceptive processes. In parallel, we characterized the caffeine metabolism in Drosophila, and highlighted a direct involvement of CYP6d5 in the degradation of caffeine into theobromine. This work shows for the first time, a direct implication of cytochromes P450 in sensory perception mechanisms and in the metabolism of caffeine in Drosophila.
Published: 2014

5. Mise au point d'un microsystème électrophorétique pour l'analyse des hydrocarbures aromatiques polycycliques dans les huiles alimentaires

Author: Ferey, Ludivine
Subjects: SDV:BBM, Molecularly imprinted polymers, Edible oils, Microchips, Capillary electrophoresis, Polycyclic aromatic hydrocarbons, Microsystèmes, Polymères à empreintes moléculaires, Huiles alimentaires, Hydrocarbures aromatiques polycycliques, Électrophorèse capillaire
Abstract: Les hydrocarbures aromatiques polycycliques (HAP) sont des contaminants de notre environnement et de notre alimentation. En raison de leur toxicité, la Commission européenne a réglementé leur teneur dans les denrées alimentaires et notamment dans les huiles. Les industriels des corps gras ont donc pour obligation de vérifier la conformité de leurs produits. Dans ce contexte, le groupe Lesieur souhaiterait développer un nouvel outil analytique rapide et portable. Ainsi, ce vaste projet de recherche vise à concevoir un microsystème électrophorétique capable d'analyser les HAP dans les huiles alimentaires. Première étude à s'inscrire dans ce projet, ce travail de thèse a donc consisté à développer de nouveaux protocoles analytiques. Dans une première partie, des méthodes de séparation des HAP ont été développées en électrophorèse capillaire (CE) modifiée par des cyclodextrines couplée à un détecteur de fluorescence induite par laser. En suivant des stratégies multivariées basées sur les plans d'expériences, deux méthodes de séparation ont été optimisées. Les huit HAP communs aux listes établies par l'agence de protection de l'environnement des Etats-Unis et l'agence européenne de sécurité sanitaire des aliments ont été séparés en moins de 7 min et dix-neuf HAP, également classés par ces deux organismes, ont été analysés en moins de 18 min. Ces méthodes de séparation ont été appliquées avec succès à des extraits d'huile dopés. Dans une deuxième partie, il a été question de transférer la méthode d'analyse des huit HAP au format microsystèmes. La principale difficulté rencontrée a été le manque de sensibilité du système de détection couplé aux puces. Le premier objectif a donc été d'optimiser les quantités d'échantillon injectées et les paramètres de la détection avec un composé modèle dans un tampon borate. Cependant, seulement quatre HAP sur les dix-neuf étudiés précédemment en CE ont pu être détectés. Toutefois, dans les conditions optimisées par le plan d'expériences, ils étaient séparés en moins de 4 min. Enfin, différents polymères à empreintes moléculaires (MIP) ont été synthétisés en vue d'extraire sélectivement les HAP des huiles. Après un criblage des conditions de synthèse, la sélectivité de chaque MIP a été évaluée en milieu pur en comparant sa capacité de rétention avec celle d'un polymère non-imprimé. Les huit HAP communs aux deux listes ont finalement pu être extraits sélectivement à partir d'huiles de tournesol, mais avec des rendements d'extraction encore insuffisants et qui nécessitent une amélioration de la procédure d'extraction., Polycyclic aromatic hydrocarbons (PAHs) are widespread contaminants in the environment and food products. Given their toxicity, their concentrations are regulated by the European Commission in food products and especially in edible oils. Consequently, manufacturers of fat products have to verify the conformity of their products. In this context, Lesieur wants to develop a rapid and portable new analytical tool. Hence, this ambitious research project aims at developing a capillary electrophoresis microchip for PAH analysis in edible oils. This PhD study, first one involved in this project, consisted in developing new analytical protocols.In a first part, PAH separation methods were developed by cyclodextrin-modified capillary electrophoresis (CE) with laser-induced fluorescence detection. Using experimental design-based strategies, two separation methods were optimized. The 8 PAHs in common between the United States Environmental Protection Agency and the European Food Safety Authority lists of priority pollutants were separated in less than 7 min, while 19 PAHs, also targeted by these institutions, were separated in less than 18 min. These CE separation methods were successfully applied to the analysis of spiked edible oil extracts.The second part aimed at transferring the electrophoretic separation method of the 8 PAHs from the capillary to the microsystem format. The lack of sensitivity of the detection system hyphenated with chips was the main difficulty encountered. Thus, injected sample amounts and detection parameters were first optimized with a model compound in a borate buffer. However, only 4 out of the 19 PAHs, previously studied in CE, could be detected. Nevertheless, under conditions predicted by the design of experiments, they were baseline resolved in less than 4 min.Finally, several molecularly imprinted polymers (MIPs) were synthesized for the selective extraction of PAHs from oils. After a screening of synthesis conditions, the selectivity of each MIP was evaluated in pure media by comparing the extraction recoveries obtained on MIP with those obtained on a non-imprinted polymer. Finally, the 8 PAHs in common between the two lists were selectively extracted from sunflower oils, but with low recoveries. Improvements in extraction procedures are still required.
Published: 2013

6. AT_CHLORO: a chloroplast protein database dedicated to sub-plastidial localization

Author: Christophe eBruley, Véronique eDupierris, Daniel eSalvi, Norbert eRolland, Myriam eFerro, Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV) (BIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Martin-Laffon, Jacqueline
Subjects: 0106 biological sciences, Proteomics, Arabidopsis thaliana, proteome, review, plant, Review Article, Computational biology, Plant Science, lcsh:Plant culture, computer.software_genre, 01 natural sciences, Chloroplast membrane, envelope membrane, chloroplast, database, protein, plastidial localization, proteomics, 03 medical and health sciences, Stroma, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:SB1-1110, 030304 developmental biology, sub-plastidial localization, 0303 health sciences, biology, biology.organism_classification, Chloroplast, Chloroplast envelope, Thylakoid, Proteome, Data mining, Chloroplast Proteins, computer, 010606 plant biology & botany
Abstract: International audience; AT_CHLORO (www.grenoble.prabi.fr/at_chloro) is a database dedicated to sub-plastidial localization of A. thaliana chloroplast proteins. This information was infered from proteomics experiments obtained from a comprehensive study that allowed the identification of proteins from envelope, stroma, and thylakoid sub-compartments Ferro et al., 2010. In addition to current knowledge regarding sub-plastidial localization, AT_CHLORO provides experimental data that allowed curated information regarding subcellular localizations of chloroplast proteins to be given. A specific focus was given to proteins that were identified in envelope fractions and for which expert functional annotation was provided. The present mini review shows the specificities of AT_CHLORO with respect to available information, data export options and recent improvements in data representation.
Published: 2012
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7. Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum

Author: Nicolas Terrapon, Laurent Brehelin, Eric Maréchal, Olivier Gascuel, Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute für Evolution and Biodiverstät, Westfälische Wilhelms-Universität Münster (WWU), Méthodes et Algorithmes pour la Bioinformatique (MAB), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Proteomics, Proteome, Amino Acid Motifs, computer.software_genre, protein domain identification, Biochemistry, Structural Biology, Hidden Markov model, Databases, Protein, lcsh:QH301-705.5, sequence alignment, Pfam database, human parasite, Plasmodium falciparum, 0303 health sciences, Multiple sequence alignment, Applied Mathematics, Methodology Article, 030302 biochemistry & molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Markov Chains, 3. Good health, Computer Science Applications, Identification (information), Molecular Sequence Annotation, lcsh:R858-859.7, Bio-informatique, Data mining, Algorithms, Bioinformatics, Protein domain, Context (language use), Computational biology, Biology, lcsh:Computer applications to medicine. Medical informatics, Domain (software engineering), 03 medical and health sciences, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Markov chain, Proteins, lcsh:Biology (General), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], computer, SDV:BIBS, Software
Abstract: Background Hidden Markov Models (HMMs) are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such as P. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains. Results Using P. falciparum as an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD) procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values. Conclusion We show that the new approaches allow identification of several domain families previously absent in the P. falciparum proteome and the Apicomplexa phylum, and identify many domains that are not detected by previous approaches. In terms of the number of new discovered domains, the new approaches outperform the previous ones when no close species are available or when they are used to identify likely occurrences among potential domains with high E-values. All predictions on P. falciparum have been integrated into a dedicated website which pools all known/new annotations of protein domains and functions for this organism. A software implementing the two proposed approaches is available at the same address: http://www.lirmm.fr/~terrapon/HMMfit/
Published: 2012
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8. Characterization of MADS-domain transcription factor complexes in Arabidopsis flower development

Author: Jose M. Muiño, Adrie H. Westphal, Jacqueline Busscher-Lange, Shujing Liu, Robert Blanvillain, Cristel C. Carles, Cezary Smaczniak, Richard G. H. Immink, Gerco C. Angenent, Kerstin Kaufmann, François Parcy, Quy Dung Dinh, Lin Xu, Marco Busscher, Sjef Boeren, Centre for BioSystems Genomics, Laboratory of Molecular Biology, Wageningen University and Research [Wageningen] (WUR), Business Unit Bioscience, Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), National Laboratory of Plant Molecular Genetics, Shangai Institute of Plant Physiology and ecology, Laboratory of Biochemistry, Grants from the Netherlands Proteomics Centre and Centre for BioSystems Genomics. - Netherlands Genomics Initiative Horizon Grant 93519020 - Netherlands Organisation for Scientific Research VIDI grant - the French National Agency Young Researcher grant for the ChromFlow project - Centre National de la Recherche Scientifique Higher Education Chair Program, Wageningen University and Research Centre [Wageningen] (WUR), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0106 biological sciences, floral quartets, Arabidopsis thaliana, Arabidopsis, plant, time genes, dna-binding, 01 natural sciences, Interactome, Biochemistry, Chromatography, Affinity, Mass Spectrometry, meristem identity, transcriptional regulation, MADS domain protein, transcription factor, Genetics, 0303 health sciences, Multidisciplinary, biology, EPS-1, chromatin activation, food and beverages, Biological Sciences, floral tissue, Cell biology, PRI Bioscience, Laboratory of Molecular Biology, protein complex isolation, Homeotic gene, TBX1, homeodomain proteins, animal structures, Biochemie, MADS Domain Proteins, Flowers, chromatin immunoprecipitation, in-vitro, Chromatin remodeling, 03 medical and health sciences, SDV:BBM, Laboratorium voor Moleculaire Biologie, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, BIOS Plant Development Systems, Transcription factor, 030304 developmental biology, pound-foolish, flowering, Arabidopsis Proteins, histone marks, fungi, biology.organism_classification, reproductive development, repression, Chromatin immunoprecipitation, 010606 plant biology & botany
Abstract: International audience; Floral organs are specified by the combinatorial action of MADS-domain transcription factors, yet the mechanisms by which MADS-domain proteins activate or repress the expression of their target genes and the nature of their cofactors are still largely unknown. Here, we show using affinity purification and mass spectrometry that five major floral homeotic MADS-domain proteins (AP1, AP3, PI, AG, and SEP3) interact in floral tissues as proposed in the "floral quartet" model. In vitro studies confirmed a flexible composition of MADS-domain protein complexes depending on relative protein concentrations and DNA sequence. In situ bimolecular fluorescent complementation assays demonstrate that MADS-domain proteins interact during meristematic stages of flower development. By applying a targeted proteomics approach we were able to establish a MADS-domain protein interactome that strongly supports a mechanistic link between MADS-domain proteins and chromatin remodeling factors. Furthermore, members of other transcription factor families were identified as interaction partners of floral MADS-domain proteins suggesting various specific combinatorial modes of action.
Published: 2012
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9. A simple and efficient method for the long-term preservation of plant cell suspension cultures

Author: Corinne Rivasseau, Anne-Marie Boisson, Richard Bligny, Elisabeth Gout, Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0106 biological sciences, phosphate starvation, Programmed cell death, Arabidopsis thaliana, Plant cell suspension, Cell, plant, cell culture, method, cell suspension, cell preservation, Acer pseudoplatanus, in vitro, in vivo, NMR, nuclear magnetic resonance, low temperature, Plant Science, lcsh:Plant culture, 01 natural sciences, Suspension culture, 03 medical and health sciences, In vivo, Botany, SDV:BBM, Genetics, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:SB1-1110, lcsh:QH301-705.5, 030304 developmental biology, 0303 health sciences, biology, Cell growth, Methodology, biology.organism_classification, Plant cell, Cell biology, medicine.anatomical_structure, in vitro and in vivo NMR spectroscopy, lcsh:Biology (General), Cell culture, 010606 plant biology & botany, Biotechnology
Abstract: Background The repeated weekly subculture of plant cell suspension is labour intensive and increases the risk of variation from parental cells lines. Most of the procedures to preserve cultures are based on controlled freezing/thawing and storage in liquid nitrogen. However, cells viability after unfreezing is uncertain. The long-term storage and regeneration of plant cell cultures remains a priority. Results Sycamore (Acer pseudoplatanus) and Arabidopsis cell were preserved over six months as suspensions cultures in a phosphate-free nutrient medium at 5°C. The cell recovery monitored via gas exchange measurements and metabolic profiling using in vitro and in vivo 13C- and 31P-NMR took a couple of hours, and cell growth restarted without appreciable delay. No measurable cell death was observed. Conclusion We provide a simple method to preserve physiologically homogenous plant cell cultures without subculture over several months. The protocol based on the blockage of cell growth and low culture temperature is robust for heterotrophic and semi-autotrophic cells and should be adjustable to cell lines other than those utilised in this study. It requires no specialized equipment and is suitable for routine laboratory use.
Published: 2012
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10. Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines

Author: Chun-Long Chen, Benjamin Audit, Guillaume Guilbaud, Arach Goldar, Yves d'Aubenton-Carafa, Alain Arneodo, Antoine Baker, Olivier Hyrien, Cédric Vaillant, Benoit Moindrot, Claude Thermes, Fabien Mongelard, Antoine Leleu, Aurélien Rappailles, Laboratoire Joliot Curie, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche under project REFOPOL (ANR 10 BLAN 1615 01), and by grants from the Fondation pour la Recherche Médicale (équipe labélisée), the ARC and the Ligue contre le Cancer (Comité de Paris) to O.H. A.R was supported by the ANR NT05-3_41825 and by a fellowship from the Conseil Regional d'Ile de France (DIM STEM-Pôle), G.G. was supported by the Ministère de l'Education Nationale de l'Enseignement Supérieur et de la Recherche, and by the Association pour la Recherche sur le Cancer., École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Autard, Delphine
Subjects: DNA Replication, Molecular Sequence Data, Biophysics, Replication Origin, Pre-replication complex, Cell Line, DNA replication factor CDT1, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Minichromosome maintenance, Control of chromosome duplication, Nucleic Acids, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Computer Simulation, Molecular Biology, Biology, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Replication timing, Genome, Ecology, biology, Base Sequence, Models, Genetic, Genome, Human, Physics, DNA replication, Chromosome Mapping, Computational Biology, DNA, Genomics, Cell biology, Licensing factor, Computational Theory and Mathematics, lcsh:Biology (General), Modeling and Simulation, biology.protein, Origin recognition complex, Epigenetics, 030217 neurology & neurosurgery, Research Article
Abstract: In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome., Author Summary DNA replication in human cells requires the parallel progression along the genome of thousands of replication machineries. Comprehensive knowledge of genetic inheritance at different development stages relies on elucidating the mechanisms that regulate the location and progression of these machineries throughout the duration of the DNA synthetic phase of the cell cycle. Here, we determine in multiple human cell types the existence of a new type of megabase-sized replication domains across which the average orientation of the replication machinery changes in a linear manner. These domains are revealed in 7 somatic cell types by a U-shaped pattern in the replication timing profiles as well as by N-shaped patterns in the DNA compositional asymmetry profile reflecting the existence of a replication-associated mutational asymmetry in the germline. These domains therefore correspond to a robust mode of replication across cell types and during evolution. Using genome-wide data on the frequency of interaction of distant chromatin segments in two cell lines, we find that these U/N-replication domains remarkably correspond to self-interacting folding units of the chromatin fiber.
Published: 2012
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11. Where does the alignment score distribution shape come from?

Author: Olivier Bastien, Philippe Ortet, Laboratoire d'Ecologie Microbienne de la Rhizosphère et d'Environnements Extrêmes (LEMIRE), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), 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)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Biologie végétale et microbiologie environnementale - UMR7265 (BVME), Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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 Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-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)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Computer science, lcsh:Evolution, Sequence alignment, Sequence space, 03 medical and health sciences, 0302 clinical medicine, Genetics, lcsh:QH359-425, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, mutual information, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Original Research, 0303 health sciences, Sequence, sequence alignment scores, business.industry, Karlin-Altchul theorem, sequence space, Pattern recognition, Mutual information, Data science, Computer Science Applications, Distribution (mathematics), Face (geometry), Generalized extreme value distribution, Probability distribution, Artificial intelligence, business, 030217 neurology & neurosurgery
Abstract: Alignment algorithms are powerful tools for searching for homologous proteins in databases, providing a score for each sequence present in the database. It has been well known for 20 years that the shape of the score distribution looks like an extreme value distribution. The extremely large number of times biologists face this class of distributions raises the question of the evolutionary origin of this probability law. We investigated the possibility of deriving the main properties of sequence alignment score distributions from a basic evolutionary process: a duplication-divergence protein evolution process in a sequence space. Firstly, the distribution of sequences in this space was defined with respect to the genetic distance between sequences. Secondly, we derived a basic relation between the genetic distance and the alignment score. We obtained a novel score probability distribution which is qualitatively very similar to that of Karlin-Altschul but performing better than all other previous model.
Published: 2011
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12. The cyst-dividing bacterium Ramlibacter tataouinensis TTB310 genome reveals a well-stocked toolbox for adaptation to a desert environment

Author: Valérie Barbe, Pedro M. Coutinho, Yves Quentin, Philippe Noirot, Thierry Heulin, Michael Dubow, Bernard Henrissat, Mireille Ansaldi, Gilles De Luca, Philippe Ortet, Cécile Jourlin-Castelli, Olivier Bastien, Romé Voulhoux, Vincent Méjean, Sylvain Fochesato, Jean Weissenbach, Béatrice Py, Frédéric Barras, Eric Maréchal, Irina Mihalcescu, André Verméglio, Wafa Achouak, Alain Filloux, Mohamed Barakat, Gwennaele Fichant, Laboratoire d'Ecologie Microbienne de la Rhizosphère et d'Environnements Extrêmes (LEMIRE), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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), Biologie végétale et microbiologie environnementale - UMR7265 (BVME), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Ministry of Higher Education and Research, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: bacteria, Ramlibacter tataouinensis, extreme environment adaptation, desiccation tolerance, cell cycle, cyst division, oxidative stress tolerance, DNA repair, carbohydrate metabolism, enzyme, fatty acid biosynthesis, membrane glycerolipid, envelope transport systems, genome sequencing, phylogeny, IV PILI, Light, Cell division, TWITCHING MOTILITY, CIRCADIAN CLOCK, Genome, Desiccation tolerance, Cell Movement, Microbial Physiology, TATAHOUINE METEORITE, Betaproteobacteria, Genetics, 0303 health sciences, Multidisciplinary, biology, Strain (chemistry), Hydrolysis, Fatty Acids, Polysaccharides, Bacterial, STRUCTURAL INSIGHTS, Genomics, Adaptation, Physiological, Circadian Rhythm, Multidisciplinary Sciences, Protein Transport, ESCHERICHIA-COLI, Science & Technology - Other Topics, Medicine, Desert Climate, Cell Division, Research Article, Signal Transduction, PROTEIN SECRETION, DNA, Bacterial, General Science & Technology, Membrane Fluidity, Science, SIGNAL-TRANSDUCTION, Genome Complexity, Microbiology, WATER CHANNEL, Microbial Ecology, Comamonadaceae, Membrane Lipids, 03 medical and health sciences, Osmotic Pressure, MD Multidisciplinary, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biology, Cell Shape, 030304 developmental biology, Science & Technology, Bacterial Evolution, 030306 microbiology, BIOFILM FORMATION, Cell Membrane, Computational Biology, Trehalose, Bacteriology, Sequence Analysis, DNA, biology.organism_classification, Oxidative Stress, Genome Expression Analysis, Extracellular Space, Desiccation, Genome, Bacterial
Abstract: International audience; Ramlibacter tataouinensis TTB310(T) (strain TTB310), a betaproteobacterium isolated from a semi-arid region of South Tunisia (Tataouine), is characterized by the presence of both spherical and rod-shaped cells in pure culture. Cell division of strain TTB310 occurs by the binary fission of spherical "cyst-like" cells ("cyst-cyst" division). The rod-shaped cells formed at the periphery of a colony (consisting mainly of cysts) are highly motile and colonize a new environment, where they form a new colony by reversion to cyst-like cells. This unique cell cycle of strain TTB310, with desiccation tolerant cyst-like cells capable of division and desiccation sensitive motile rods capable of dissemination, appears to be a novel adaptation for life in a hot and dry desert environment. In order to gain insights into strain TTB310's underlying genetic repertoire and possible mechanisms responsible for its unusual lifestyle, the genome of strain TTB310 was completely sequenced and subsequently annotated. The complete genome consists of a single circular chromosome of 4,070,194 bp with an average G+C content of 70.0%, the highest among the Betaproteobacteria sequenced to date, with total of 3,899 predicted coding sequences covering 92% of the genome. We found that strain TTB310 has developed a highly complex network of two-component systems, which may utilize responses to light and perhaps a rudimentary circadian hourglass to anticipate water availability at the dew time in the middle/end of the desert winter nights and thus direct the growth window to cyclic water availability times. Other interesting features of the strain TTB310 genome that appear to be important for desiccation tolerance, including intermediary metabolism compounds such as trehalose or polyhydroxyalkanoate, and signal transduction pathways, are presented and discussed.
Published: 2011
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13. Identification of plant-like galactolipids in Chromera velia, a photosynthetic relative of malaria parasites

Author: Cyrille Y. Botté, Jan Janouškovec, Thusita Rupasinghe, Eric Maréchal, Geoffrey I. McFadden, Ross L. Coppel, Paul K. Crellin, Patrick J. Keeling, Yoshiki Yamaryo-Botté, Malcolm J. McConville, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), School of Botany [Melbourne], Faculty of Science [Melbourne], University of Melbourne-University of Melbourne, Department of Microbiology [Monash University, Australia], School of Biomedical Sciences [Monash University, Clayton], Monash University [Clayton]-Monash University [Clayton], Botany Department, University of British Columbia (UBC), University of Melbourne, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Botany [Vancouver] (UBC Botany), European Research Council, National Health and Medical Research Council of Australia, CNRS, Agence Nationale de la Recherche, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0106 biological sciences, Plasmodium, Plastid localization, Plastid Evolution, Protozoan Proteins, Chromera velia, MESH: Amino Acid Sequence, photosynthetic eukaryotes, 01 natural sciences, Biochemistry, MGDG, Plastids, MESH: Protozoan Proteins, MESH: Evolution, Molecular, 0303 health sciences, biology, Endosymbiosis, food and beverages, Galactolipids, MESH: Plastids, Lipids, Chromera, 3. Good health, apicomplexa, galactosyltransferase, galactolipid, Toxoplasma, DGDG, Evolution, Molecular Sequence Data, MESH: Apicomplexa, Galactolipid/Galactosyltransferase, malaria, human parasite, Chloroplast, Models, Biological, Glycerolipid, Evolution, Molecular, Apicomplexa, Membrane Lipids, 03 medical and health sciences, Mass Spectrometry (MS), lipid, digalactosyldiacylglycerol, Apicoplast, plastid localization, parasitic diseases, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Plastid, Molecular Biology, 030304 developmental biology, MESH: Molecular Sequence Data, fungi, MESH: Models, Biological, Plasmodium falciparum, Cell Biology, monogalactosyldiacyglycerol, biology.organism_classification, enzyme, MESH: Galactolipids, biosynthesis, Molecular, Models, Biological, 010606 plant biology & botany
Abstract: International audience; Apicomplexa are protist parasites that include Plasmodium spp., the causative agents of malaria, and Toxoplasma gondii, responsible for toxoplasmosis. Most Apicomplexa possess a relict plastid, the apicoplast, which was acquired by secondary endosymbiosis of a red alga. Despite being nonphotosynthetic, the apicoplast is otherwise metabolically similar to algal and plant plastids and is essential for parasite survival. Previous studies of Toxoplasma gondii identified membrane lipids with some structural features of plastid galactolipids, the major plastid lipid class. However, direct evidence for the plant-like enzymes responsible for galactolipid synthesis in Apicomplexan parasites has not been obtained. Chromera velia is an Apicomplexan relative recently discovered in Australian corals. C. velia retains a photosynthetic plastid, providing a unique model to study the evolution of the apicoplast. Here, we report the unambiguous presence of plant-like monogalactosyldiacylglycerol and digalactosyldiacylglycerol in C. velia and localize digalactosyldiacylglycerol to the plastid. We also provide evidence for a plant-like biosynthesis pathway and identify candidate galactosyltranferases responsible for galactolipid synthesis. Our study provides new insights in the evolution of these important enzymes in plastid-containing eukaryotes and will help reconstruct the evolution of glycerolipid metabolism in important parasites such as Plasmodium and Toxoplasma.
Published: 2011
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14. Adaptation of Alternaria brassicicola to the plant host : studies of molecular pathway involved in the protection of the pathogenic fungal in front of the Brassicaceae indolic phytoalexin

Author: Joubert, Aymeric
Subjects: SDV:BC, SDV:BBM, compensatory mechanism, phytoalexin, camalexin, brassinin, Alternaria brassicicola, black spot, pouvoir pathogène, détournement des défenses, phytoalexines, camalexine, brassinine, UPR, CWI, HOG
Abstract: Alternaria brassicicola is a necrotrophic fungal pathogen responsible for the black spotdisease of Brassicaceae that causes major damages in fields. During host infection, A.brassicicola is exposed to high levels of defence compounds, such as the indolicphytoalexins called camalexin and brassinin. Previous studies showed that thesecompounds probably cause damage to fungal membranes and activate a compensatorymechanism in fungal cells aimed at preserving membrane integrity. The aim of this thesisconsists in investigating the molecular basis of this mechanism. The results show that theunfolded protein response (UPR) and two MAPK signalling pathways, the cell wallintegrity (CWI) and the high osmolarity glycerol (HOG) were activated in A. brassicicolain response to phytoalexin exposure. Mutant strains lacking functional MAP kinases orAbHacA, the major UPR transcription regulator, showed in vitro hypersusceptibility tocamalexin and brassinin. Replacement mutants exhibited a loss or an attenuation of thevirulence on host plants that may partially result from their inability to cope with defencemetabolites such as indolic phytoalexins. This study constitutes the first evidence that aphytoalexin activates fungal MAP kinases and UPR, and that outputs of activated pathwayscontribute to protecting the fungus against antimicrobial plant metabolites. A functionalmodel of fungal signalling pathways regulated by camalexin is proposed and leads toconsider new promising strategies for disease control., Alternaria brassicicola est un champignon nécrotrophe responsable du « black spot » desBrassicaceae, causant d’importants dégâts culturaux. Lors de l’infection, les Brassicaceaesynthétisent divers composés de défense tels que les phytoalexines indoliques camalexineet brassinine. Une étude préalable avait suggéré une action de ces molécules sur l’intégritéde la membrane fongique et la mise en place chez le champignon d’un mécanismeadaptatif de type compensatoire visant à renforcer son intégrité cellulaire. L’objectif de lathèse est d’identifier les composantes moléculaires régulant l’induction de ce mécanisme.Les travaux réalisés montrent que les voies de signalisation HOG, CWI, et UPR impliquéesrespectivement dans la régulation de l’osmose cellulaire, la biosynthèse de la paroi et laréponse au stress de sécrétion sont activées chez A. brassicicola lors de l’exposition auxphytoalexines. Le phénotypage de mutants déficients pour des composantes clés de cestrois voies de signalisation montre qu’ils sont plus sensibles aux phytoalexines etprésentent une baisse de leur agressivité in planta (AbSlt2Δ pour la voie CWI, AbHog1Δpour la voie HOG) ou une perte de virulence (AbhacAΔ pour la voie UPR). Cette étudeillustre le rôle crucial des voies de signalisation dans l’adaptation d’un champignonphytopathogène aux stress liés à la colonisation de son hôte et donc dans la réussite ducycle infectieux. Ce rôle clé en fait de bons candidats comme cibles pour la définition destratégies de lutte contre l’alternariose.
Published: 2011

15. How Fitch-Margoliash Algorithm can Benefit from Multi Dimensional Scaling

Author: Delphine Grando, Sylvain Lespinats, Olivier Bastien, Eric Maréchal, Mohamed-Ali Hakimi, Olivier Tenaillon, Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Agence Nationale de la Recherche, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Computer science, lcsh:Evolution, 02 engineering and technology, Least squares, Field (computer science), Sammon mapping, 03 medical and health sciences, Fitch-Margoliash, Multi Dimensional Scaling, Least Square methods, Sammon's mapping, molecular phylogeny, SDV:BBM, lcsh:QH359-425, 0202 electrical engineering, electronic engineering, information engineering, Genetics, Point (geometry), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Multidimensional scaling, Limit (mathematics), Ecology, Evolution, Behavior and Systematics, Original Research, 030304 developmental biology, 0303 health sciences, Dimensionality reduction, Computer Science Applications, Tree (data structure), Sammon’s mapping, 020201 artificial intelligence & image processing, Algorithm
Abstract: Whatever the phylogenetic method, genetic sequences are often described as strings of characters, thus molecular sequences can be viewed as elements of a multi-dimensional space. As a consequence, studying motion in this space (ie, the evolutionary process) must deal with the amazing features of high-dimensional spaces like concentration of measured phenomenon. To study how these features might influence phylogeny reconstructions, we examined a particular popular method: the Fitch-Margoliash algorithm, which belongs to the Least Squares methods. We show that the Least Squares methods are closely related to Multi Dimensional Scaling. Indeed, criteria for Fitch-Margoliash and Sammon's mapping are somewhat similar. However, the prolific research in Multi Dimensional Scaling has definitely allowed outclassing Sammon's mapping. Least Square methods for tree reconstruction can now take advantage of these improvements. However, “false neighborhood” and “tears” are the two main risks in dimensionality reduction field: “false neighborhood” corresponds to a widely separated data in the original space that are found close in representation space, and neighbor data that are displayed in remote positions constitute a “tear”. To address this problem, we took advantage of the concepts of “continuity” and “trustworthiness” in the tree reconstruction field, which limit the risk of “false neighborhood” and “tears”. We also point out the concentration of measured phenomenon as a source of error and introduce here new criteria to build phylogenies with improved preservation of distances and robustness. The authors and the Evolutionary Bioinformatics Journal dedicate this article to the memory of Professor W.M. Fitch (1929–2011).
Published: 2011
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16. Activation of the chloroplast monogalactosyldiacylglycerol synthase MGD1 by phosphatidic acid and phosphatidylglycerol

Author: Yoshiki Yamaryo, Eric Maréchal, Maryse A. Block, Emmanuelle Dubots, Christelle Breton, Magali Audry, Hiroyuki Ohta, Olivier Bastien, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Center for Biological Resources and Informatics, and Research Center for the Evolving Earth and Planets, Tokyo Institute of Technology [Tokyo] (TITECH), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), inconnu, and Inconnu
Subjects: 0106 biological sciences, Chloroplasts, enzymatic activity, Arabidopsis, plant, monogalactosyldiacylglycerol, MESH: Galactosyltransferases, 01 natural sciences, Biochemistry, Chloroplast membrane, MGDG, chemistry.chemical_compound, Spinacia oleracea, MESH: Arabidopsis, membrane, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Phosphatidic Acids, MESH: Spinacia oleracea, food and beverages, Phosphatidylglycerols, Phosphatidic acid, Galactosyltransferases, Lipids, Chloroplast, MESH: Plant Leaves, Monogalactosyldiacylglycerol synthase, DGDG, MESH: Enzyme Activation, Galactolipid, Phosphatidic Acids, MESH: Arabidopsis Proteins, Biology, 03 medical and health sciences, lipids biosynthesis, chloroplast, digalactosyldiacylglycerol, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, phosphatidylglycerol, MESH: Phosphatidylglycerols, Molecular Biology, phospholipids, 030304 developmental biology, Diacylglycerol kinase, Phosphatidylglycerol, MESH: Phospholipids, metabolism, galactolipids, MGDG synthase, Arabidopsis Proteins, Enzyme Activation, Galactolipids, Phospholipids, Plant Leaves, MESH: Chloroplasts, Cell Biology, MESH: Galactolipids, chemistry, Membrane biogenesis, biology.protein, 010606 plant biology & botany
Abstract: International audience; One of the major characteristics of chloroplast membranes is their enrichment in galactoglycerolipids, monogalactosyldiacylglycerol (MGDG), and digalactosyldiacylglycerol (DGDG), whereas phospholipids are poorly represented, mainly as phosphatidylglycerol (PG). All these lipids are synthesized in the chloroplast envelope, but galactolipid synthesis is also partially dependent on phospholipid synthesis localized in non-plastidial membranes. MGDG synthesis was previously shown essential for chloroplast development. In this report, we analyze the regulation of MGDG synthesis by phosphatidic acid (PA), which is a general precursor in the synthesis of all glycerolipids and is also a signaling molecule in plants. We demonstrate that under physiological conditions, MGDG synthesis is not active when the MGDG synthase enzyme is supplied with its substrates only, i.e. diacylglycerol and UDP-gal. In contrast, PA activates the enzyme when supplied. This is shown in leaf homogenates, in the chloroplast envelope, as well as on the recombinant MGDG synthase, MGD1. PG can also activate the enzyme, but comparison of PA and PG effects on MGD1 activity indicates that PA and PG proceed through different mechanisms, which are further differentiated by enzymatic analysis of point-mutated recombinant MGD1s. Activation of MGD1 by PA and PG is proposed as an important mechanism coupling phospholipid and galactolipid syntheses in plants.
Published: 2010
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17. Assessing Functional Annotation Transfers with Inter-Species Conserved Coexpression: Application to Plasmodium Falciparum

Author: Eric Maréchal, Laurent Brehelin, Isabelle Florent, Olivier Gascuel, Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: lcsh:QH426-470, lcsh:Biotechnology, Plasmodium falciparum, Protozoan Proteins, malaria, Ribosome biogenesis, Saccharomyces cerevisiae, 03 medical and health sciences, Annotation, probabilistic model, 0302 clinical medicine, Ribosomal protein, lcsh:TP248.13-248.65, Human parasite, Apicomplexa, sequences homology, gene expression, annotation transfer, ontology, SDV:BBM, Melanogaster, Genetics, Cluster Analysis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, Conserved Sequence, 030304 developmental biology, 0303 health sciences, biology, Models, Genetic, Gene Expression Profiling, Computational Biology, Gene Annotation, Sequence Analysis, DNA, biology.organism_classification, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, lcsh:Genetics, DNA microarray, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome, Protozoan, 030217 neurology & neurosurgery, Algorithms, Biotechnology, Research Article
Abstract: Background Plasmodium falciparum is the main causative agent of malaria. Of the 5 484 predicted genes of P. falciparum, about 57% do not have sufficient sequence similarity to characterized genes in other species to warrant functional assignments. Non-homology methods are thus needed to obtain functional clues for these uncharacterized genes. Gene expression data have been widely used in the recent years to help functional annotation in an intra-species way via the so-called Guilt By Association (GBA) principle. Results We propose a new method that uses gene expression data to assess inter-species annotation transfers. Our approach starts from a set of likely orthologs between a reference species (here S. cerevisiae and D. melanogaster) and a query species (P. falciparum). It aims at identifying clusters of coexpressed genes in the query species whose coexpression has been conserved in the reference species. These conserved clusters of coexpressed genes are then used to assess annotation transfers between genes with low sequence similarity, enabling reliable transfers of annotations from the reference to the query species. The approach was used with transcriptomic data sets of P. falciparum, S. cerevisiae and D. melanogaster, and enabled us to propose with high confidence new/refined annotations for several dozens hypothetical/putative P. falciparum genes. Notably, we revised the annotation of genes involved in ribosomal proteins and ribosome biogenesis and assembly, thus highlighting several potential drug targets. Conclusions Our approach uses both sequence similarity and gene expression data to help inter-species gene annotation transfers. Experiments show that this strategy improves the accuracy achieved when using solely sequence similarity and outperforms the accuracy of the GBA approach. In addition, our experiments with P. falciparum show that it can infer a function for numerous hypothetical genes.
Published: 2010
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18. Trace elements in glucometabolic disorders: an update

Author: Jean-Robert Rapin, Nicolas Wiernsperger, Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB), BMC, Ed., Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Review, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, medicine, Internal Medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, Biochemical reactions, Glucose homeostasis, In patient, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Beneficial effects, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:RC620-627, 030304 developmental biology, 0303 health sciences, business.industry, medicine.disease, 3. Good health, Trace (semiology), lcsh:Nutritional diseases. Deficiency diseases, business
Abstract: International audience; Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed.
Published: 2010
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19. Bioinformatic strategies to provide functional clues to the unknown genes in Plasmodium falciparum genome

Author: Laurent Brehelin, Eric Maréchal, Isabelle Florent, Olivier Gascuel, Muséum national d'Histoire naturelle (MNHN), Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche ANR-06-CIS6-MDCA-14-01, Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Méthodes et Algorithmes pour la Bioinformatique (MAB), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Plasmodium, Transcription, Genetic, Proteome, Genes, Protozoan, Proteomics, 01 natural sciences, Genome, novel mining methods, Gene Expression Regulation, Fungal, annotations, Malaria, Falciparum, 0303 health sciences, biology, bioinformatics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Fungal, Protozoan, DECIPHER, Transcription, Falciparum, medicine.medical_specialty, Veterinary (miscellaneous), Plasmodium falciparum, malaria, Computational biology, Saccharomyces cerevisiae, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Genetic, Molecular genetics, gene annotations, SDV:BBM, medicine, Animals, Humans, lcsh:RC109-216, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, 030304 developmental biology, Base Sequence, Computational Biology, Gene Annotation, data mining, biology.organism_classification, Human parasite, Gene Expression Regulation, Genes, Insect Science, genome, Malaria, Animal Science and Zoology, Parasitology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome, Protozoan, 010606 plant biology & botany
Abstract: The fight against Plasmodium falciparum, the species responsible for 90% of the lethal forms of human malaria, took a new direction with the publication of its genome in 2002. However, the hopes that the genome should help bringing to the foreground the expected new "vaccines candidates" or "targets of new medicines" were disappointed by the low number of genes that could be functionally annotated--less than 40% upon the genome publication, just over 50% eight years later. This 10% gain of knowledge was made possible by the efforts of the entire scientific community in many directions which include: the production of transcriptomic and proteomic profiles at various stages of the parasite development and in response to drug or stress treatments; the proteomic study of subcellular compartments; the sequencing of numerous Plasmodium related species (allowing whole genome comparisons) and the sequencing of numerous P. falciparum strains (allowing investigations of gene polymorphism). In parallel with this production of experimental biological data, the development of original mining tools adapted to the P falciparum specificities quickly appeared as a priority, as the performances of "classical" bioinformatic tools, used successfully for other genomes, had limited efficacy. This was the aim of the PlasmoExplore project launched in 2007. This brief review does not cover all efforts made by the international community to decipher the P falciparum genome but focuses on improvements and novel mining methods investigated by the PlasmoExplore consortium, and some of the lessons we could learn from these efforts., La lutte contre Plasmodium falciparum, l’espèce responsable de 90 % des formes mortelles du paludisme chez l’Homme, a pris une nouvelle direction avec la publication de son génome en 2002. Cependant, les espoirs de faire émerger de nouveaux « candidats de vaccins » ou des « cibles de nouveaux médicaments » ont été déçus par le faible nombre de gènes qui ont pu être annotés sur le plan fonctionnel – moins de 40 % au moment de la publication de son génome, juste au-delà de 50 % huit ans plus tard. Ce gain de 10 % de connaissances (parfois imprécises) résulte des efforts menés par toute la communauté scientifique dans plusieurs directions dont : la production de profils transcriptomiques et protéomiques au cours du développement du parasite et en réponse à des traitements médicamenteux ou stressants ; l’étude protéomique de compartiments subcellulaires ; le séquençage d’une diversité d’espèces proches du genre Plasmodium et dans le genre Plasmodium (permettant des comparaisons au niveau de génome entiers) et le séquençage de nombreuses souches de P. falciparum (permettant d’accéder au polymorphisme des gènes). En parallèle de cette production de données biologiques expérimentales, le développement d’outils bioinformatiques originaux adaptés aux spécificités de P. falciparum est rapidement apparu comme une priorité, face aux limitations rencontrées avec les outils classiques, utilisés pourtant avec succès sur d’autres génomes. C’est ce défi que le consortium PlasmoExplore, lancé en 2007, s’est proposé de relever. Cette revue ne couvre pas tous les efforts réalisés par la communauté internationale pour décrypter le génome de P. falciparum, mais se focalise sur les améliorations aux méthodes classiques et les développements de méthodes originales nouvelles que le consortium PlasmoExplore a mis en œuvre, ainsi que les leçons que l’on peut tirer de tels efforts.
Published: 2010
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20. Melanoma Cells Treated with GGTI and IFN-gamma Allow Murine Vaccination and Enhance Cytotoxic Response against Human Melanoma Cells

Author: Gilles Favre, Anne-Françoise Tilkin-Mariamé, Christine Pich, Raphael Moriez, Philippe Rochaix, Guillaume Sarrabayrouse, Virginie Armand-Labit, Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Institut Claudius Regaud, Neuro-Gastroentérologie et Nutrition (NGN), Ecole supérieure d'agriculture de Purpan (ESAP)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), This work was supported by the ‘‘Institut National de la Sante et de la Recherche Medicale' and by grants from ‘‘La Ligue contre le Cancer, Region Midi Pyrenees' and from the ‘‘Institut Claudius Regaud', Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Institut National de la Recherche Agronomique (INRA)-Ecole supérieure d'agriculture de Purpan (ESAP), and Autard, Delphine
Subjects: Cytotoxicity, Immunologic, T-Lymphocytes, Melanoma, Experimental, lcsh:Medicine, Oncology/Skin Cancers, Jurkat cells, Jurkat Cells, Mice, Interleukin 21, 0302 clinical medicine, Cytotoxic T cell, lcsh:Science, Melanoma, 0303 health sciences, Multidisciplinary, biology, Vaccination, Flow Cytometry, Up-Regulation, 3. Good health, 030220 oncology & carcinogenesis, Benzamides, Immunology/Antigen Processing and Recognition, Cytokines, Female, Research Article, Blotting, Western, Interferon-gamma, 03 medical and health sciences, Immune system, Antigen, Cell Line, Tumor, SDV:BBM, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, CD86, CD40, lcsh:R, Histocompatibility Antigens Class I, Coculture Techniques, Mice, Inbred C57BL, Immunology/Immune Response, Immunology, Leukocytes, Mononuclear, Cancer research, biology.protein, lcsh:Q, B7-2 Antigen, CD8, Pharmacology/Drug Development
Abstract: International audience; BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I) and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298) stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL), we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC) revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i) activation of CD8 T lymphocytes (CD8+/CD69+); ii) proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+); iii) secretion of hIFN-gamma; and iv) anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.
Published: 2010
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21. The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver

Author: Grégory Chevillard, Valérie Nicolas-Francès, Stéphane Mandard, F. Hansmannel, Frank J. Gonzalez, J. A. Bonzo, Thierry Pineau, Stephen A. Duncan, Michele A. Battle, Pascal G.P. Martin, J. Chamouton, Norbert Latruffe, Marie Claude Clémencet, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Lady Davis Institute for Medical Research [Montréal], McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Laboratoire de Pharmacologie et Toxicologie, UR66, INRA, Institut National de la Recherche Agronomique (INRA), The Ministry of Research, National Education and Technology, the Regional Council of Burgundy, the GDR-CNRS no2583 on peroxisome, the French Ministry of Research, National Education and Technology., McGill University-Jewish General Hospital, Mandard, Stéphane, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, National Cancer Institute ( NIH ), Lady Davis Institute for Medical Research, McGill University, and Institut National de la Recherche Agronomique ( INRA )
Subjects: Article Subject, Response element, Peroxisome proliferator-activated receptor, Biology, 03 medical and health sciences, Transactivation, 0302 clinical medicine, Drug Discovery, Gene expression, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, Pharmacology (medical), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:QH301-705.5, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, chemistry.chemical_classification, Genetics, Endocrinology and metabolism, 0303 health sciences, Thiolase, Intron, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell biology, lcsh:Biology (General), Nuclear receptor, chemistry, 030220 oncology & carcinogenesis, Endocrinologie et métabolisme, Research Article
Abstract: PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal3-keto-acyl-CoA thiolase B(Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of theThbgene, by which PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXRα. RT-PCR performed with RNA from liver-specific HNF4α-null mice confirmed the involvement of HNF4α in the PPARα-regulated induction ofThbby Wy14,643. Overall, we conclude that HNF4α enhances the PPARα-mediated activation ofThbgene expression in part through interaction with the obligate PPARα partner, RXRα.
Published: 2010
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22. Rodent and nonrodent malaria parasites differ in their phospholipid metabolic pathways

Author: Henri Vial, Sandrine Déchamps, Eric Maréchal, Marjorie Maynadier, Sharon Wein, Laila Gannoun-Zaki, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Dynamique moléculaire des interactions membranaires (DMIM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: MESH: Signal Transduction, Plasmodium, Plasmodium vinckei, Plasmodium berghei, Phosphatidylethanolamine N-Methyltransferase, MESH: Amino Acid Sequence, Biochemistry, Serine, chemistry.chemical_compound, Mice, Endocrinology, MESH: Animals, MESH: Phylogeny, Phylogeny, 0303 health sciences, biology, 030302 biochemistry & molecular biology, Phosphatidylserine, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Phosphatidylethanolamine N-methyltransferase, Phosphatidylcholines, Female, serine decarboxylase, Metabolic Networks and Pathways, Research Article, Signal Transduction, phosphatidylserine, Plasmodium falciparum, Molecular Sequence Data, MESH: Malaria, malaria, MESH: Sequence Alignment, MESH: Phosphatidylethanolamines, QD415-436, 03 medical and health sciences, lipid, parasitic diseases, SDV:BBM, Animals, huma parasite, metabolism, phospholipid, biosynthesis, metabolic pathway, phosphatidylcholine, phosphatidylethanolamine, enzyme, phosphoethanolamine N-methyltransferase, Amino Acid Sequence, Malaria, Phosphatidylethanolamines, Sequence Alignment, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Serine, MESH: Mice, 030304 developmental biology, Phosphatidylethanolamine, MESH: Molecular Sequence Data, MESH: Plasmodium, Cell Biology, MESH: Phosphatidylcholines, biology.organism_classification, chemistry, MESH: Metabolic Networks and Pathways, MESH: Phosphatidylethanolamine N-Methyltransferase, phospholipid biosynthesis, MESH: Female
Abstract: International audience; Malaria, a disease affecting humans and other animals, is caused by a protist of the genus Plasmodium. At the intraerythrocytic stage, the parasite synthesizes a high amount of phospholipids through a bewildering number of pathways. In the human Plasmodium falciparum species, a plant-like pathway that relies on serine decarboxylase and phosphoethanolamine N-methyltransferase activities diverts host serine to provide additional phosphatidylcholine and phosphatidylethanolamine to the parasite. This feature of parasitic dependence toward its host was investigated in other Plasmodium species. In silico analyses led to the identification of phosphoethanolamine N-methyltransferase gene orthologs in primate and bird parasite genomes. However, the gene was not detected in the rodent P. berghei, P. yoelii, and P. chabaudi species. Biochemical experiments with labeled choline, ethanolamine, and serine showed marked differences in biosynthetic pathways when comparing rodent P. berghei and P. vinckei, and human P. falciparum species. Notably, in both rodent parasites, ethanolamine and serine were not significantly incorporated into phosphatidylcholine, indicating the absence of phosphoethanolamine N-methyltransferase activity. To our knowledge, this is the first study to highlight a crucial difference in phospholipid metabolism between Plasmodium species. The findings should facilitate efforts to develop more rational approaches to identify and evaluate new targets for antimalarial therapy.
Published: 2009
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23. Exact distribution of a pattern in a set of random sequences generated by a Markov source: applications to biological data

Author: Anne-Claude Camproux, Gregory Nuel, Leslie Regad, Juliette Martin, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique génomique et moléculaire ((U 726)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Molécules Thérapeutiques in silico (MTI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Statistique et Génome ( SG ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Bioinformatique génomique et moléculaire, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Molécules Thérapeutique in silico, Recherche de molécules à visée thérapeutique par approches In Silico ( MTI ), Unité Mathématique, Informatique et Génome ( MIG ), Institut National de la Recherche Agronomique ( INRA ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Unité Mathématique Informatique et Génome (MIG), BMC, Ed., and Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Theoretical computer science, lcsh:QH426-470, Computer science, Markov model, 01 natural sciences, Set (abstract data type), 010104 statistics & probability, 03 medical and health sciences, Structural Biology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, Upstream (networking), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 0101 mathematics, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:QH301-705.5, 030304 developmental biology, 0303 health sciences, Biological data, Markov chain, Variable-order Markov model, Applied Mathematics, Research, Random sequence, lcsh:Genetics, Computational Theory and Mathematics, lcsh:Biology (General), Large set (Ramsey theory), Algorithm
Abstract: Background In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.). Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models. Results The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence. Conclusions Our algorithms prove to be effective and able to handle real data sets with multiple sequences, as well as biological patterns of interest, even when the latter display a high complexity (PROSITE signatures for example). In addition, these exact algorithms allow us to avoid the edge effect observed under the single sequence approximation, which leads to erroneous results, especially when the marginal distribution of the model displays a slow convergence toward the stationary distribution. We end up with a discussion on our method and on its potential improvements.
Published: 2009
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24. Lactococcus lactis, an alternative system for functional expression of peripheral and intrinsic Arabidopsis membrane proteins

Author: Lucas Moyet, Norbert Rolland, Jacques Joyard, Annie Frelet-Barrand, Aurélien Deniaud, Sylvain Boutigny, Daniel Salvi, Pierre Richaud, Daphné Seigneurin-Berny, Eva Pebay-Peyroula, Florent Bernaudat, Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Echanges Membranaires et Signalisation (LEMS), Université de la Méditerranée - Aix-Marseille 2-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: DNA, Complementary, Arabidopsis thaliana, Biochemistry/Membrane Proteins and Energy Transduction, Science, Genetic Vectors, Molecular Sequence Data, plant, membrane protein, expression system, recombinant protein, bacteria, Lactococcus lactis, Heterologous, Plant Biology/Plant Biochemistry and Physiology, 03 medical and health sciences, Open Reading Frames, Arabidopsis, Gene expression, SDV:BBM, Biotechnology/Applied Microbiology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Expression vector, biology, Base Sequence, 030306 microbiology, cDNA library, Arabidopsis Proteins, biology.organism_classification, Biochemistry, Membrane protein, Medicine, Electrophoresis, Polyacrylamide Gel, Heterologous expression, Biotechnology/Bioengineering, Research Article
Abstract: International audience; BACKGROUND: Despite their functional and biotechnological importance, the study of membrane proteins remains difficult due to their hydrophobicity and their low natural abundance in cells. Furthermore, into established heterologous systems, these proteins are frequently only produced at very low levels, toxic and mis- or unfolded. Lactococcus lactis, a gram-positive lactic bacterium, has been traditionally used in food fermentations. This expression system is also widely used in biotechnology for large-scale production of heterologous proteins. Various expression vectors, based either on constitutive or inducible promoters, are available for this system. While previously used to produce bacterial and eukaryotic membrane proteins, the ability of this system to produce plant membrane proteins was until now not tested. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to test the expression, in Lactococcus lactis, of either peripheral or intrinsic Arabidopsis membrane proteins that could not be produced, or in too low amount, using more classical heterologous expression systems. In an effort to easily transfer genes from Gateway-based Arabidopsis cDNA libraries to the L. lactis expression vector pNZ8148, we first established a cloning strategy compatible with Gateway entry vectors. Interestingly, the six tested Arabidopsis membrane proteins could be produced, in Lactococcus lactis, at levels compatible with further biochemical analyses. We then successfully developed solubilization and purification processes for three of these proteins. Finally, we questioned the functionality of a peripheral and an intrinsic membrane protein, and demonstrated that both proteins were active when produced in this system. CONCLUSIONS/SIGNIFICANCE: Altogether, these data suggest that Lactococcus lactis might be an attractive system for the efficient and functional production of difficult plant membrane proteins.
Published: 2009
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25. Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes

Author: Cécile Neuvéglise, Rym Kachouri-Lafond, Joël Acker, Christian Marck, Claude Gaillardin, Christophe Ozanne, Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Microbiologie et Génétique Moléculaire (MGM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Molecular Sequence Data, Gene Dosage, Gene Expression, Yarrowia, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Genome, RNA polymerase III, Evolution, Molecular, 03 medical and health sciences, 5S ribosomal RNA, RNA, Transfer, Transcription Factor TFIIIA, SDV:BBM, Genetics, RNA Precursors, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Internal transcribed spacer, Gene, Molecular Biology, 030304 developmental biology, SDV:BC, 0303 health sciences, Base Sequence, 030302 biochemistry & molecular biology, RNA, Ribosomal, 5S, Genetic Variation, Promoter, Genes, rRNA, Ribosomal RNA, RNA, Transfer, Trp, Phenotype, Gene Fusion, Genome, Fungal
Abstract: International audience; In eukaryotes, genes transcribed by RNA polymerase III (Pol III) carry their own internal promoters and as such, are transcribed as individual units. Indeed, a very few cases of dicistronic Pol III genes are yet known. In contrast to other hemiascomycetes, 5S rRNA genes of Yarrowia lipolytica are not embedded into the tandemly repeated rDNA units, but appear scattered throughout the genome. We report here an unprecedented genomic organization: 48 over the 108 copies of the 5S rRNA genes are located 3' of tRNA genes. We show that these peculiar tRNA-5S rRNA dicistronic genes are expressed in vitro and in vivo as Pol III transcriptional fusions without the need of the 5S rRNA gene-specific factor TFIIIA, the deletion of which displays a viable phenotype. We also report the existence of a novel putative non-coding Pol III RNA of unknown function about 70 nucleotide-long (RUF70), the 13 genes of which are devoid of internal Pol III promoters and located 3' of the 13 copies of the tDNA-Trp (CCA). All genes embedded in the various dicistronic genes, fused 5S rRNA genes, RUF70 genes and their leader tRNA genes appear to be efficiently transcribed and their products correctly processed in vivo.
Published: 2008
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26. Subcellular localization and dynamics of a digalactolipid-like epitope in Toxoplasma gondii

Author: Ruth Welti, Henri J. Vial, Nadia Saidani, Marie-France Cesbron-Delauw, Ernest Mui, Corinne Mercier, Giorgis Isaac, Eric Maréchal, Cyrille Y. Botté, Mónica Mondragón, Ricardo Mondragón, Rima McLeod, Jean-François Dubremetz, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Departamento de Bioquimica, CINVESTAV del IPN, Kansas Lipidomics Research Center, Division of Biology, Kansas State University, Departments of Ophthalmology and Visual Sciences, University of Chicago, ANR PlasmoExplore,ANR PlasmoExplore, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-06-MDCA-0014,PlasmoExplore,Fouille des données génomiques de Plasmodium falciparum pour prédire la fonction des gènes orphelins et identifier de nouvelles cibles thérapeutiques(2006), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Chloroplasts, Intracellular Space, Biochemistry, Cell membrane, Epitopes, Immunolabeling, Endocrinology, Spinacia oleracea, subcellular localization, Microscopy, Immunoelectron, membrane, mass spectrometry, 0303 health sciences, epitope, 030302 biochemistry & molecular biology, 3. Good health, Cell biology, medicine.anatomical_structure, membrane domains, inner membrane complex, Rabbits, Toxoplasma, human parasite, Apicomplexa, Toxoplasma gondii, apicoplast, lipid, digalactolipid, digalactosyldiacylglycerol, immunolabelling, immunofluorescence, immunoelectron microscopy, Immunoelectron microscopy, QD415-436, Biology, Antibodies, Cell Line, 03 medical and health sciences, parasitic diseases, medicine, SDV:BBM, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, digalactosyldiacylglcycerol, 030304 developmental biology, Apicoplast, Inner membrane complex, galactolipids, Cell Membrane, Cell Biology, Subcellular localization, biology.organism_classification, Actins, Rats
Abstract: Toxoplasma gondii is a unicellular parasite characterized by unique extracellular and intracellular membrane compartments. The lipid composition of subcellular membranes has not been determined, limiting our understanding of lipid homeostasis, control, and trafficking, a series of processes involved in pathogenesis. In addition to a mitochondrion, Toxoplasma contains a plastid called the apicoplast. The occurrence of a plastid raised the question of the presence of chloroplast galactolipids. Using three independent rabbit and rat antibodies against digalactosyldiacylglycerol (DGDG) from plant chloroplasts, we detected a class of Toxoplasma lipids harboring a digalactolipid-like epitope (DGLE). Immunolabeling characterization supports the notion that the DGLE polar head is similar to that of DGDG. Mass spectrometry analyses indicated that dihexosyl lipids having various hydrophobic moieties (ceramide, diacylglycerol, and acylalkylglycerol) might react with anti-DGDG, but we cannot exclude the possibility that more complex dihexosyl-terminated lipids might also be immunolabeled. DGLE localization was analyzed by immunofluorescence and immunoelectron microscopy and confirmed by subcellular fractionation. No immunolabeling of the apicoplast could be observed. DGLE was scattered in pellicle membrane domains in extracellular tachyzoites and was relocalized to the anterior tip of the cell upon invasion in an actin-dependent manner, providing insights on a possible role in pathogenetic processes. DGLE was detected in other Apicomplexa (i.e., Neospora, Plasmodium, Babesia, and Cryptosporidium).
Published: 2008
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27. DNA physical properties determine nucleosome occupancy from yeast to fly

Author: Claude Thermes, Yves d'Aubenton-Carafa, Vincent Miele, Thierry Grange, Cédric Vaillant, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Agence Nationale de la Recherche, ACI, Centre National de la Recherche Scientifique, French Ministère de l'Education et de la Recherche, ANR: 06-PCVI-2006, NT05-1_41977,06-PCVI-2006, NT05-1_41977, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and ANR-06-PCVI-0006,CMIDT,Controlled Membrane Interaction and Destabilisation for DNA Transfer(2006)
Subjects: Models, Molecular, chemistry.chemical_compound, 0302 clinical medicine, Models, Yeasts, MESH: Animals, MESH: Models, Genetic, Promoter Regions, Genetic, Genetics, 0303 health sciences, biology, MESH: Yeasts, MESH: Genomics, MESH: DNA, Genomics, MESH: Saccharomyces cerevisiae, MESH: Gene Expression Regulation, Chromatin, Nucleosomes, DNA-Binding Proteins, MESH: Promoter Regions (Genetics), Histone, Drosophila melanogaster, Fungal, MESH: Nucleic Acid Conformation, Thermodynamics, Promoter Regions (Genetics), MESH: Thermodynamics, MESH: Models, Molecular, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Genes, Fungal, Computational biology, Saccharomyces cerevisiae, DNA-binding protein, MESH: Drosophila melanogaster, 03 medical and health sciences, Genetic, MESH: Nucleosomes, SDV:BBM, Nucleosome, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Models, Genetic, Eukaryotic transcription, Molecular, Promoter, DNA, Linker DNA, chemistry, Gene Expression Regulation, Genes, Nucleic Acid Conformation, biology.protein, MESH: Genes, Fungal, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins
Abstract: Epigénome er paléogénomie; International audience; Nucleosome positioning plays an essential role in cellular processes by modulating accessibility of DNA to proteins. Here, using only sequence-dependent DNA flexibility and intrinsic curvature, we predict the nucleosome occupancy along the genomes of Saccharomyces cerevisiae and Drosophila melanogaster and demonstrate the predictive power and universality of our model through its correlation with experimentally determined nucleosome occupancy data. In yeast promoter regions, the computed average nucleosome occupancy closely superimposes with experimental data, exhibiting a
Published: 2008
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28. A pig multi-tissue normalised cDNA library: large-scale sequencing, cluster analysis and 9K micro-array resource generation

Author: Marcelo B. Soares, Karine Hugot, Gwenola Tosser-Klopp, Maria de Fatima Bonaldo, Agnès Bonnet, François Hatey, Francis Benne, Eddie Iannuccelli, Laboratoire de Génétique Cellulaire (LGC), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire de radiobiologie et d'étude du génome (LREG), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Children's Memorial Research Center, Northwestern University, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: Swine, Transcriptome, 0302 clinical medicine, OVARIAN-FOLLICLES, Cluster Analysis, EXPRESSION PATTERNS, MESH: Animals, PORCINE SKELETAL-MUSCLE, GENE DISCOVERY, TAGS ESTS, IDENTIFICATION, CONSTRUCTION, DATABASE, PROJECT, RETINA, Animals, Computational Biology, Expressed Sequence Tags, Gene Expression Profiling, Gene Library, Oligonucleotide Array Sequence Analysis, Sequence Analysis, MESH: Swine, Genetics, 0303 health sciences, Expressed sequence tag, Contig, 030220 oncology & carcinogenesis, DNA microarray, Biotechnology, Research Article, MESH: Computational Biology, lcsh:QH426-470, Sequence analysis, lcsh:Biotechnology, Biology, MESH: Expressed Sequence Tags, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Sequence Analysis, Complementary DNA, lcsh:TP248.13-248.65, MESH: Gene Library, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, cDNA library, MESH: Cluster Analysis, lcsh:Genetics, MESH: Oligonucleotide Array Sequence Analysis, Large-Scale Sequencing
Abstract: Background Domestic animal breeding and product quality improvement require the control of reproduction, nutrition, health and welfare in these animals. It is thus necessary to improve our knowledge of the major physiological functions and their interactions. This would be greatly enhanced by the availability of expressed gene sequences in the databases and by cDNA arrays allowing the transcriptome analysis of any function. The objective within the AGENAE French program was to initiate a high-throughput cDNA sequencing program of a 38-tissue normalised library and generate a diverse microarray for transcriptome analysis in pig species. Results We constructed a multi-tissue cDNA library, which was normalised and subtracted to reduce the redundancy of the clones. Expressed Sequence Tags were produced and 24449 high-quality sequences were released in EMBL database. The assembly of all the public ESTs (available through SIGENAE website) resulted in 40786 contigs and 54653 singletons. At least one Agenae sequence is present in 11969 contigs (12.5%) and in 9291 of the deeper-than-one-contigs (22.8%). Sequence analysis showed that both normalisation and subtraction processes were successful and that the initial tissue complexity was maintained in the final libraries. A 9K nylon cDNA microarray was produced and is available through CRB-GADIE. It will allow high sensitivity transcriptome analyses in pigs. Conclusion In the present work, a pig multi-tissue cDNA library was constructed and a 9K cDNA microarray designed. It contributes to the Expressed Sequence Tags pig data, and offers a valuable tool for transcriptome analysis.
Published: 2008
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29. Comparative secretome analyses of two Trichoderma reesei RUT-C30 and CL847 hypersecretory strains

Author: Frédéric Monot, Gwénaël Jan, Sabrina Lignon, Daniel Mollé, Marcel Asther, Antoine Margeot, Jean Claude Sigoillot, Alain Dolla, Hughes Mathis, Isabelle Herpoël-Gimbert, Interactions et Modulateurs de Réponses (IMR), Centre National de la Recherche Scientifique (CNRS), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: MALDI-TOF, lcsh:Biotechnology, Lignocellulosic biomass, Cellulase, Management, Monitoring, Policy and Law, complex mixtures, 7. Clean energy, Applied Microbiology and Biotechnology, lcsh:Fuel, 03 medical and health sciences, lcsh:TP315-360, Bioenergy, lcsh:TP248.13-248.65, Lc ms ms, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Food science, LC-MS/MS, BIOTECHNOLOGIE, PROTEOME, Trichoderma reesei, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, biology, 030306 microbiology, Renewable Energy, Sustainability and the Environment, business.industry, Research, food and beverages, biology.organism_classification, Biotechnology, enzyme, General Energy, Biofuel, protéine, biology.protein, business
Abstract: Background Due to its capacity to produce large amounts of cellulases, Trichoderma reesei is increasingly been researched in various fields of white biotechnology, especially in biofuel production from lignocellulosic biomass. The commercial enzyme mixtures produced at industrial scales are not well characterized, and their proteinaceous components are poorly identified and quantified. The development of proteomic methods has made it possible to comprehensively overview the enzymes involved in lignocellulosic biomass degradation which are secreted under various environmental conditions. Results The protein composition of the secretome produced by industrial T. reesei (strain CL847) grown on a medium promoting the production of both cellulases and hemicellulases was explored using two-dimensional electrophoresis and MALDI-TOF or LC-MS/MS protein identification. A total of 22 protein species were identified. As expected, most of them are potentially involved in biomass degradation. The 2D map obtained was then used to compare the secretomes produced by CL847 and another efficient cellulolytic T. reesei strain, Rut-C30, the reference cellulase-overproducing strain using lactose as carbon source and inducer of cellulases. Conclusion This study provides the most complete mapping of the proteins secreted by T. reesei to date. We report on the first use of proteomics to compare secretome composition between two cellulase-overproducing strains Rut-C30 and CL847 grown under similar conditions. Comparison of protein patterns in both strains highlighted many unexpected differences between cellulase cocktails. The results demonstrate that 2D electrophoresis is a promising tool for studying cellulase production profiles, whether for industrial characterization of an entire secretome or for a more fundamental study on cellulase expression at genome-wide scale.
Published: 2008
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30. Analyzing stochastic transcription to elucidate the nucleoid's organization

Author: Alain Hénaut, Alessandra Riva, Angélique Chéron, Anne-Sophie Carpentier, Frédérique Barloy-Hubler, Systématique, adaptation, évolution (SAE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Rival, Alain, Soluscience, Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and Leballeur, Philippe
Subjects: Transcription, Genetic, lcsh:QH426-470, lcsh:Biotechnology, Intracellular Space, Bacillus subtilis, Models, Biological, 03 medical and health sciences, chemistry.chemical_compound, Transcription (biology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:TP248.13-248.65, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, SDV:BBM, Nucleoid, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Replicon, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Sinorhizobium meliloti, Stochastic Processes, biology, 030302 biochemistry & molecular biology, Gene Expression Regulation, Bacterial, biology.organism_classification, lcsh:Genetics, chemistry, Evolutionary biology, DNA microarray, DNA, Research Article, Biotechnology
Abstract: Background The processes of gene transcription, translation, as well as the reactions taking place between gene products, are subject to stochastic fluctuations. These stochastic events are being increasingly examined as it emerges that they can be crucial in the cell's survival. In a previous study we had examined the transcription patterns of two bacterial species (Escherichia coli and Bacillus subtilis) to elucidate the nucleoid's organization. The basic idea is that genes that share transcription patterns, must share some sort of spatial relationship, even if they are not close to each other on the chromosome. We had found that picking any gene at random, its transcription will be correlated with genes at well-defined short – as well as long-range distances, leaving the explanation of the latter an open question. In this paper we study the transcription correlations when the only transcription taking place is stochastic, in other words, no active or "deterministic" transcription takes place. To this purpose we use transcription data of Sinorhizobium meliloti. Results Even when only stochastic transcription takes place, the co-expression of genes varies as a function of the distance between genes: we observe again the short-range as well as the regular, long-range correlation patterns. Conclusion We explain these latter with a model based on the physical constraints acting on the DNA, forcing it into a conformation of groups of a few successive large and transcribed loops, which are evenly spaced along the chromosome and separated by small, non-transcribed loops. We discuss the question about the link between shared transcription patterns and physiological relationship and come to the conclusion that when genes are distantly placed along the chromosome, the transcription correlation does not imply a physiological relationship.
Published: 2008
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31. Organization of cellulose synthase complexes involved in primary cell wall synthesis in Arabidopsis thaliana

Author: François Parcy, Samantha Vernhettes, Herman Höfte, Thierry Desprez, Martine Gonneau, Michal Juraniec, Zaneta Pochylova, Elizabeth Faris Crowell, Hélène Jouy, Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Department of Plant Biotechnology, Plant Breeding and Acclimatization Institute, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0106 biological sciences, Arabidopsis thaliana, MESH: Plant Shoots, Arabidopsis, CESA, MESH: Plant Roots, plant, MESH: Protein Isoforms, cellulose synthase, 01 natural sciences, Plant Roots, Bimolecular fluorescence complementation, chemistry.chemical_compound, Gene Expression Regulation, Plant, catalytic subunit, MESH: Genes, Plant, Protein Isoforms, MESH: Arabidopsis, MESH: Cellulose, MESH: Models, Genetic, 0303 health sciences, Multidisciplinary, biology, ATP synthase, Cell wall, isoform, Biological Sciences, ARABIDOPSIS THALIANA, PROTEIN, CELLULOSE, MUTANT, cellulose, MESH: Microfibrils, Biochemistry, Glucosyltransferases, Plant Shoots, Gene isoform, MESH: Arabidopsis Proteins, Genes, Plant, 03 medical and health sciences, MESH: Cell Wall, Cellulose synthase complex, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cellulose, MESH: Gene Expression Regulation, Plant, 030304 developmental biology, MESH: Glucosyltransferases, Models, Genetic, Arabidopsis Proteins, biology.organism_classification, biosynthesis, enzyme, gene expression, Cell Wall, Gene Expression Regulation, Plant, Genes, Microfibrils, Models, Genetic, chemistry, biology.protein, Biophysics, 010606 plant biology & botany
Abstract: In all land plants, cellulose is synthesized from hexameric plasma membrane complexes. Indirect evidence suggests that in vascular plants the complexes involved in primary wall synthesis contain three distinct cellulose synthase catalytic subunits (CESAs). In this study, we show that CESA3 and CESA6 fused to GFP are expressed in the same cells and at the same time in the hypocotyl of etiolated seedlings and migrate with comparable velocities along linear trajectories at the cell surface. We also show that CESA3 and CESA6 can be coimmunoprecipitated from detergent-solubilized extracts, their protein levels decrease in mutants for either CESA3 , CESA6 , or CESA1 and CESA3, CESA6 and also CESA1 can physically interact in vivo as shown by bimolecular fluorescence complementation. We also demonstrate that CESA6-related CESA5 and CESA2 are partially, but not completely, redundant with CESA6 and most likely compete with CESA6 for the same position in the cellulose synthesis complex. Using promoter-β-glucuronidase fusions we show that CESA5 , CESA6 , and CESA2 have distinct overlapping expression patterns in hypocotyl and root corresponding to different stages of cellular development. Together, these data provide evidence for the existence of binding sites for three distinct CESA subunits in primary wall cellulose synthase complexes, with two positions being invariably occupied by CESA1 and CESA3, whereas at least three isoforms compete for the third position. Participation of the latter three isoforms might fine-tune the CESA complexes for the deposition of microfibrils at distinct cellular growth stages.
Published: 2007
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32. A tale of two oxidation states: bacterial colonization of arsenic-rich environments

Author: Caroline Dossat, Barbara Schoepp, Jean Weissenbach, Yuko Makita, Valérie Barbe, Patricia Siguier, Béatrice Segurens, Michael Chandler, Wolfgang Nitschke, Sophie Mangenot, Zoé Rouy, Stéphanie Weiss, David Vallenet, Benoit Cournoyer, Diliana D. Simeonova, Philippe Ortet, Antoine Danchin, Florence Arsène-Ploetze, Sandrine Koechler, Christine Carapito, Mohamed Barakat, Evelyne Krin, Didier Lièvremont, Daniel Muller, Emmanuelle Leize, Simon Duval, Philippe N. Bertin, Marie-Claire Lett, Nicolas Perdrial, Michaël Heymann, Stéphane Cruveiller, Aurélie Lieutaud, Violaine Bonnefoy, Evelyne Turlin, Claudine Médigue, Emmanuel Talla, Alain Van Dorsselaer, Génétique moléculaire, génomique, microbiologie (GMGM), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire d'Ecologie Microbienne de la Rhizosphère et d'Environnements Extrêmes (LEMIRE), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Génétique des Génomes Bactériens, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de géochimie de la surface (CGS), Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut national des sciences de l'Univers (INSU - CNRS), Structure et évolution des génomes (SEG), CNS-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Génétique moléculaire, génomique, microbiologie ( GMGM ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Genoscope - Centre national de séquençage [Evry] ( GENOSCOPE ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire d'Ecologie Microbienne de la Rhizosphère et d'Environnements Extrêmes ( LEMIRE ), Université de la Méditerranée - Aix-Marseille 2-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de chimie bactérienne ( LCB ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pluridisciplinaire Hubert Curien ( IPHC ), Laboratoire de microbiologie et génétique moléculaires ( LMGM ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de géochimie de la surface ( CGS ), Institut national des sciences de l'Univers ( INSU - CNRS ) -Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Structure et évolution des génomes ( SEG ), and CNS-Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Oxidation-Reduction, Cancer Research, Drug Resistance, MESH : Models, Biological, QH426-470, MESH : Carbon, MESH : Drug Resistance, Bacterial, MESH: Genome, Bacterial, Arsenic, Bacteria, Biodegradation, Environmental, Carbon, Bacterial, Energy Metabolism, Genome, Metals, Models, Biological, Oxidation-Reduction, Phylogeny, MESH: Biodegradation, Environmental, 0302 clinical medicine, Herminiimonas arsenicoxydans, MESH: Phylogeny, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), 0303 health sciences, Ecology, MESH: Energy Metabolism, MESH : Arsenic, 6. Clean water, Biodegradation, Environmental, Research Article, inorganic chemicals, MESH : Biodegradation, Environmental, MESH : Genome, Bacterial, Energy metabolism, chemistry.chemical_element, MESH: Carbon, Biology, Genomic databases, Microbiology, Models, Biological, 03 medical and health sciences, Bacterial colonization, Bioremediation, Drug Resistance, Bacterial, MESH: Arsenic, MESH: Drug Resistance, Bacterial, SDV:BBM, Genetics, MESH : Bacteria, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH : Oxidation-Reduction, MESH: Metals, 030306 microbiology, MESH : Metals, MESH: Models, Biological, MESH : Phylogeny, Computational Biology, Oxidation reduction, Genetics and Genomics, biology.organism_classification, Archaea, MESH : Energy Metabolism, Eubacteria, MESH: Bacteria, Positive chemotaxis, chemistry, 13. Climate action, Genome, Bacterial, 030217 neurology & neurosurgery
Abstract: Microbial biotransformations have a major impact on contamination by toxic elements, which threatens public health in developing and industrial countries. Finding a means of preserving natural environments—including ground and surface waters—from arsenic constitutes a major challenge facing modern society. Although this metalloid is ubiquitous on Earth, thus far no bacterium thriving in arsenic-contaminated environments has been fully characterized. In-depth exploration of the genome of the β-proteobacterium Herminiimonas arsenicoxydans with regard to physiology, genetics, and proteomics, revealed that it possesses heretofore unsuspected mechanisms for coping with arsenic. Aside from multiple biochemical processes such as arsenic oxidation, reduction, and efflux, H. arsenicoxydans also exhibits positive chemotaxis and motility towards arsenic and metalloid scavenging by exopolysaccharides. These observations demonstrate the existence of a novel strategy to efficiently colonize arsenic-rich environments, which extends beyond oxidoreduction reactions. Such a microbial mechanism of detoxification, which is possibly exploitable for bioremediation applications of contaminated sites, may have played a crucial role in the occupation of ancient ecological niches on earth., Author Summary Microorganisms play a crucial role in nutrient biogeochemical cycles. Arsenic is found throughout the environment from both natural and anthropogenic sources. Its inorganic forms are highly toxic and impair the physiology of most higher organisms. Arsenic contamination of groundwater supplies is giving rise to increasingly severe human health problems in both developing and industrial countries. In the present work, we investigated the metabolism of this metalloid in Herminiimonas arsenicoxydans, a representative organism of a novel bacterial genus widespread in aquatic environments. Examination of the genome sequence and experimental evidence revealed that it is remarkably capable of coping with arsenic. Our observations support the existence of multiple strategies allowing arsenic-metabolizing microbes to efficiently colonize toxic environments. In particular, arsenic oxidation and scavenging may have played a crucial role in the development of early stages of life on Earth. Such mechanisms may one day be exploited as part of a potential bioremediation strategy in toxic environments.
Published: 2007
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33. Cytosolic HPPK/DHPS from Arabidopsis thaliana: A specific role in stress response

Author: Storozhenko, Sergei, Navarette, Oscar, Ravanel, Stéphane, de Brouwer, Veerle, Chaerle, Peter, Zhang, Guo-Fang, Bastien, Olivier, Lambert, Willy, Rébeillé, Fabrice, van Der Straeten, Dominique, Unit of Plant Hormone Signalling and Bioimaging, Department of Molecular Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Laboratory of Toxicology, State University of Ghent, Ghent University [Belgium] (UGENT), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: tetrahydrofolate biosynthesis, plant, Arabidopsis thaliana, vitamin B9, folate, enzyme, bifunctional enzyme, 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase, dihydropteroate synthase, subcellular localization, cytosol, gene expression, stress, salt stress, oxidative stress, osmotic stress, seed development, seed germination, parasitic diseases, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; In plants, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8- dihydropteroate synthase (mitHPPK/DHPS) is a bifunctional mitochondrial enzyme, which catalyses the first two consecutive steps of tetrahydrofolate biosynthesis. Mining the Arabidopsis genome database has revealed a second gene encoding a protein that lacks a potential transit peptide, suggesting a cytosolic localization of the isoenzyme (cytHPPK/DHPS). When the N-terminal part of the cytHPPK/DHPS was fused to GFP, the fusion protein appeared only in the cytosol, confirming the above prediction. Functionality of cytHPPK/DHPS was addressed by two parallel approaches: first, the cytHPPK/DHPS was able to rescue yeast mutants lacking corresponding activities; second, recombinant cytHPPK/DHPS expressed and purified from E. coli displayed both HPPK and DHPS activities in vitro. In contrast to mitHPPK/DHPS, which was ubiquitously expressed, the cytHPPK/DHPS gene was exclusively expressed in reproductive tissue, more precisely in developing seeds as revealed by histochemical analysis of a transgenic cytHPPK/DHPS promoter-GUS line. In addition, it was observed that expression of cytHPPK/DHPS mRNA was induced by salt stress, suggesting a potential role of the enzyme in stress response. This was supported by the phenotype of a T-DNA insertion mutant in the cytHPPK/DHPS gene, resulting in lower germination rates as compared to the wild type upon application of oxidative and osmotic stress.
Published: 2007
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34. Knock-out of the Mg protoporphyrin IX methyltransferase gene in Arabidopsis: Effects on chloroplast development and on chloroplast-to-nucleus signaling

Author: Pontier, Dominique, Albrieux, Catherine, Joyard, Jacques, Lagrange, Thierry, Block, Maryse, Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Chlorophyll, Chloroplasts, Arabidopsis thaliana, Arabidopsis, Protoporphyrins, plant, Gene Expression Regulation, Enzymologic, Article, Gene Expression Regulation, Plant, SDV:BBM, polycyclic compounds, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, gene, Cell Nucleus, chlorophyll biosynthesis, Photosystem I Protein Complex, plastid to nucleus signaling, nuclear gene repression, Mg chelatase, Photosystem II Protein Complex, Methyltransferases, chloroplast development, enzyme, Mg protoporphyrin IX methyltransferase, knock-out mutant, post-transcriptional regulation, Cytochrome b6f Complex, Gene Deletion, Signal Transduction
Abstract: Protoporphyrin IX is the last common intermediate between the heme and chlorophyll biosynthesis pathways. The addition of magnesium directs this molecule toward chlorophyll biosynthesis. The first step downstream from the branchpoint is catalyzed by the magnesium chelatase and is a highly regulated process. The corresponding product, magnesium protoporphyrin IX, has been proposed to play an important role as a signaling molecule implicated in plastid-to-nucleus communication. To get more information on the chlorophyll biosynthesis pathway and on magnesium protoporphyrin IX derivative functions, we have identified an magnesium protoporphyrin IX methyltransferase (CHLM) knock-out mutant in Arabidopsis in which the mutation induces a blockage downstream from magnesium protoporphyrin IX and an accumulation of this chlorophyll biosynthesis intermediate. Our results demonstrate that the CHLM gene is essential for the formation of chlorophyll and subsequently for the formation of photosystems I and II and cytochrome b6f complexes. Analysis of gene expression in the chlm mutant provides an independent indication that magnesium protoporphyrin IX is a negative effector of nuclear photosynthetic gene expression, as previously reported. Moreover, it suggests the possible implication of magnesium protoporphyrin IX methyl ester, the product of CHLM, in chloroplast-to-nucleus signaling. Finally, post-transcriptional up-regulation of the level of the CHLH subunit of the magnesium chelatase has been detected in the chlm mutant and most likely corresponds to specific accumulation of this protein inside plastids. This result suggests that the CHLH subunit might play an important regulatory role when the chlorophyll biosynthetic pathway is disrupted at this particular step.
Published: 2007
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35. Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?

Author: Lyn-Marie Birkholtz, Olivier Bastien, Gordon Wells, Delphine Grando, Fourie Joubert, Vinod Kasam, Marc Zimmermann, Philippe Ortet, Nicolas Jacq, Nadia Saïdani, Sylvaine Roy, Martin Hofmann-Apitius, Vincent Breton, Abraham I Louw, Eric Maréchal, African Centre for Gene Technologies, Faculty of Natural and Agricultural Sciences-University of Pretoria [South Africa], Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Bioinformatics and Computational Biology Unit, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Physique Corpusculaire - Clermont-Ferrand (LPC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Fraunhofer Institute for Algorithms and Scientific Computing (Fraunhofer SCAI), Fraunhofer (Fraunhofer-Gesellschaft), Protéines de Protection des Végétaux (PPV), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Dynamique moléculaire des interactions membranaires (DMIM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Biologie-Informatique-Mathématique (LBIM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Fraunhofer Institute for Algorithms and Scientific Computing, Department of Bioinformatics, Laboratoire d'Ecophysiologie Moléculaire des Plantes (LEMP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2), Publica, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-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)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de physiologie cellulaire végétale ( LPCV ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Recherche Agronomique ( INRA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique Corpusculaire - Clermont-Ferrand ( LPC ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Ecophysiologie Végétale et de Microbiologie, Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Dynamique moléculaire des interactions membranaires ( DMIM ), Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Biologie-Informatique-Mathématique ( LBIM ), Faculty of Natural and Agricultural Sciences - University of Pretoria [South Africa], Université Joseph Fourier - Grenoble 1 (UJF) - Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF) - Institut National de la Recherche Agronomique (INRA) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP) - Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3) - Centre National de la Recherche Scientifique (CNRS), and Université Montpellier 2 - Sciences et Techniques (UM2) - Centre National de la Recherche Scientifique (CNRS)
Subjects: FOS: Computer and information sciences, Plasmodium, Knowledge space, Computer science, Data management, RC955-962, Protozoan Proteins, RC109-216, Review, Infectious and parasitic diseases, Ligands, Quantitative Biology - Quantitative Methods, drug target, Arctic medicine. Tropical medicine, Phylogeny, Quantitative Methods (q-bio.QM), [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, biology, 3. Good health, Infectious Diseases, Computer Science - Distributed, Parallel, and Cluster Computing, statistics, Bio-informatique, malaria, Plasmodium falciparum, genome, data mining, protein sequence comparison, molecular phylogeny, metabolic pathway, protein structure prediction, chemogenomics, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Bioinformatics, Context (language use), Computational biology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Antimalarials, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], SDV:BBM, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, lcsh:RC109-216, Quantitative Biology - Genomics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Genomics (q-bio.GN), 030306 microbiology, Drug candidate, business.industry, biology.organism_classification, medicine.disease, Chemical space, FOS: Biological sciences, Parasitology, Functional profiling, Distributed, Parallel, and Cluster Computing (cs.DC), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, Genome, Protozoan, Malaria
Abstract: The organization and mining of malaria genomic and post-genomic data is highly motivated by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should therefore be as reliable and versatile as possible. In this context, we examined five aspects of the organization and mining of malaria genomic and post-genomic data: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Progresses toward a grid-enabled chemogenomic knowledge space are discussed., Comment: 43 pages, 4 figures, to appear in Malaria Journal
Published: 2006
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36. Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine. Role of HNF4alpha, CREM, HNF1alpha, and C/EBPalpha

Author: Fabienne Rajas, Enzo Lalli, Carine Zitoun, Amandine Gautier-Stein, Gilles Mithieux, Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes (RMND), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR Laennec (IL), 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Nestlé, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Université de 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Loudig, Nadine
Subjects: Enzymologic, Male, Glucose uptake, Vasoactive intestinal peptide, MESH: Rats, Sprague-Dawley, MESH: Base Sequence, Biochemistry, Rats, Sprague-Dawley, 0302 clinical medicine, Transcriptional regulation, Cyclic AMP, MESH: CCAAT-Enhancer-Binding Protein-alpha, Glucose homeostasis, MESH: Animals, Hepatocyte Nuclear Factor 1-alpha, Intestinal Mucosa, MESH: Cyclic AMP, Cancer, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Gene Expression Regulation, Enzymologic, MESH: Vasoactive Intestinal Peptide, Intestines, Hepatocyte Nuclear Factor 4, Glucose-6-Phosphatase, MESH: Caco-2 Cells, MESH: Hepatocyte Nuclear Factor 4, Glucose 6-phosphatase, Vasoactive Intestinal Peptide, MESH: Intestines, Gene isoform, medicine.medical_specialty, MESH: Rats, Molecular Sequence Data, Médecine humaine et pathologie, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Cyclic AMP Response Element Modulator, Gene Expression Regulation, Enzymologic, Cyclic AMP Response Element Modulator, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, medicine, CCAAT-Enhancer-Binding Protein-alpha, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Hepatocyte Nuclear Factor 1-alpha, Protein kinase A, Base Sequence, Caco-2 Cells, Gene Expression Regulation, Rats, Sprague-Dawley, Molecular Biology, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Cell Biology, MESH: Glucose-6-Phosphatase, MESH: Male, Endocrinology, Gluconeogenesis, biology.protein, Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Gluconeogenesis is induced in both the liver and intestine by increased cAMP levels. However, hepatic and intestinal glucose production can have opposite effects on glucose homeostasis. Glucose release into the portal vein by the intestine increases glucose uptake and reduces food intake. In contrast, glucose production by the liver contributes to hyperglycemia in type II diabetes. Glucose-6-phosphatase (Glc6Pase) is the key enzyme of gluconeogenesis in both the liver and intestine. Here we specify the cAMP/protein kinase A regulation of the Glc6Pase gene in the intestine compared with the liver. Similarly to the liver, the molecular mechanism of cAMP/protein kinase A regulation involves cAMP-response element-binding protein, HNF4alpha, CAAT/enhancer-binding protein, and HNF1. In contrast to the situation in the liver, we find that different isoforms of CAAT/enhancer-binding protein and HNF1 contribute to the specific regulation of the Glc6Pase gene in the intestine. Moreover, we show that cAMP-response element binding modulator specifically contributes to the regulation of the Glc6Pase gene in the intestine but not in the liver. These results allow us to identify intestine-specific regulators of the Glc6Pase gene and to improve the understanding of the differences in the regulation of gluconeogenesis in the intestine compared with the liver.
Published: 2006
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37. Phosphorylation of microtubule-associated protein STOP by calmodulin kinase II

Author: Baratier, Julie, Peris, Leticia, Brocard, Jacques, Gory-Fauré, Sylvie, Dufour, Fabrice, Bosc, Christophe, Fourest-Lieuvin, Anne, Blanchoin, Laurent, Salin, Paul, Job, Didier, Andrieux, Annie, Organisation Fonctionnelle du Cytosquelette, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR27, Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Physio-pathologie des réseaux neuronaux du cycle veille-sommeil, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), This work was supported in part by grants from La Ligue Nationale contre le Cancer to D.J., Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: MESH: Protein Transport, MESH: Hippocampus, MESH: Neurons, MESH: Microscopy, Fluorescence, Actins, Animals, Brain, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinases, Calmodulin, Hippocampus, Mice, Microscopy, Fluorescence, Microtubule-Associated Proteins, Microtubules, Neurons, Phosphorylation, Protein Transport, Synapses, MESH: Actins, MESH: Synapses, MESH: Brain, SDV:BBM, MESH: Calcium-Calmodulin-Dependent Protein Kinases, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, MESH: Phosphorylation, MESH: Microtubules, MESH: Calmodulin, MESH: Microtubule-Associated Proteins, MESH: Calcium-Calmodulin-Dependent Protein Kinase Type 2
Abstract: International audience; STOP proteins are microtubule-associated, calmodulin-regulated proteins responsible for the high degree of stabilization displayed by neuronal microtubules. STOP suppression in mice induces synaptic defects affecting both short and long term synaptic plasticity in hippocampal neurons. Interestingly, STOP has been identified as a component of synaptic structures in neurons, despite the absence of microtubules in nerve terminals, indicating the existence of mechanisms able to induce a translocation of STOP from microtubules to synaptic compartments. Here we have tested STOP phosphorylation as a candidate mechanism for STOP relocalization. We show that, both in vitro and in vivo, STOP is phosphorylated by the multifunctional enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), which is a key enzyme for synaptic plasticity. This phosphorylation occurs on at least two independent sites. Phosphorylated forms of STOP do not bind microtubules in vitro and do not co-localize with microtubules in cultured differentiating neurons. Instead, phosphorylated STOP co-localizes with actin assemblies along neurites or at branching points. Correlatively, we find that STOP binds to actin in vitro. Finally, in differentiated neurons, phosphorylated STOP co-localizes with clusters of synaptic proteins, whereas unphosphorylated STOP does not. Thus, STOP phosphorylation by CaMKII may promote STOP translocation from microtubules to synaptic compartments where it may interact with actin, which could be important for STOP function in synaptic plasticity.
Published: 2006
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38. Characterization of a defensin from the oyster Crassostrea gigas. Recombinant production, folding, solution structure, antimicrobial activities, and gene expression

Author: Aumelas, André, Garnier, Julien, Fievet, Julie, Escoubas, Jean-Michel, Bulet, Philippe, Gonzalez, Marcelo, Lelong, Christophe, Favrel, Pascal, Bachère, Evelyne, Gueguen, Yannick, and Herpin, Amaury
Subjects: huître, fungi, Escherichia coli, amino acid sequence, animals, defensins, gene Expression, gram-negative bacteria, gram-positive bacteria, molecular sequence data, nuclear magnetic resonance, biomolecular, protein folding, protein structure, recombinant proteins, SDV:BBM, activité microbienne, crassostrea gigas, expression des gènes
Abstract: In invertebrates, defensins were found in arthropods and in the mussels. Here, we report for the first time the identification and characterization of a defensin (Cg-Def) from an oyster. Cg-def mRNA was isolated from Crassostrea gigas mantle using an expressed sequence tag approach. To gain insight into potential roles of Cg-Def in oyster immunity, we produced the recombinant peptide in Escherichia coli, characterized its antimicrobial activities, determined its solution structure by NMR spectroscopy, and quantified its gene expression in vivo following bacterial challenge of oysters. Recombinant Cg-Def was active in vitro against Gram-positive bacteria but showed no or limited activities against Gram-negative bacteria and fungi. The activity of Cg-Def was retained in vitro at a salt concentration similar to that of seawater. The Cg-Def structure shares the so-called cystine-stabilized alpha-beta motif (CS-alphabeta) with arthropod defensins but is characterized by the presence of an additional disulfide bond, as previously observed in the mussel defensin (MGD-1). Nevertheless, despite a similar global fold, the Cg-Def and MGD-1 structures mainly differ by the size of their loops and by the presence of two aspartic residues in Cg-Def. Distribution of Cg-def mRNA in various oyster tissues revealed that Cg-def is mainly expressed in mantle edge where it was detected by mass spectrometry analyses. Furthermore, we observed that the Cg-def messenger concentration was unchanged after bacterial challenge. Our results suggest that Cg-def gene is continuously expressed in the mantle and would play a key role in oyster by providing a first line of defense against pathogen colonization.
Published: 2006

39. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. : Vitamin E transport in enterocytes

Author: Reboul, Emmanuelle, Klein, Alexis, Bietrix, Florence, Gieize, Beatrice, Malezet-Desmoulins, Christiane, Schneider, Martina, Margotat, Alain, Lagrost, Laurent, Collet, Xavier, and Borel, Patrick
Subjects: SDV:BC, Endocrinology and metabolism, Endocrinologie et métabolisme, SDV:BBM, Absorption, Animals, Antigens, CD36, Binding, Competitive, Biological Transport, Caco-2 Cells, Cell Differentiation, Cholesterol, Dose-Response Relationship, Drug, Enterocytes, Epithelial Cells, Humans, Intestines, Lipids, Mice, Transgenic, Micelles
Abstract: Although cellular uptake of vitamin E was initially described as a passive process, recent studies in the liver and brain have shown that SR-BI (scavenger receptor class B type I) is involved in this phenomenon. As SR-BI is expressed at high levels in the intestine, the present study addressed the involvement of SR-BI in vitamin E trafficking across enterocytes. Apical uptake and efflux of the main dietary forms of vitamin E were examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium. (R,R,R)-gamma-tocopherol bioavailability was compared between wild-type mice and mice overexpressing SR-BI in the intestine. The effect of vitamin E on enterocyte SR-BI mRNA levels was measured by real-time quantitative reverse transcription-PCR. Concentration-dependent curves for vitamin E uptake were similar for (R,R,R)-alpha-, (R,R,R)-gamma-, and dl-alpha-tocopherol. (R,R,R)-alpha-tocopherol transport was dependent on incubation temperature, with a 60% reduction in absorption at 4 degrees C compared with 37 degrees C (p < 0.05). Vitamin E flux in enterocytes was directed from the apical to the basal side, with a relative 10-fold reduction in the transfer process when measured in the opposite direction (p < 0.05). Co-incubation with cholesterol, gamma-tocopherol, or lutein significantly impaired alpha-tocopherol absorption. Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 80% of vitamin E uptake and up to 30% of apical vitamin E efflux (p < 0.05), and similar results were obtained for (R,R,R)-gamma-tocopherol. SR-BI mRNA levels were not significantly modified after a 24-h incubation of Caco-2 cells with vitamin E. Finally, (R,R,R)-gamma-tocopherol bioavailability was 2.7-fold higher in mice overexpressing SR-BI than in wild-type mice (p < 0.05). The present data show for the first time that vitamin E intestinal absorption is, at least in part, mediated by SR-BI.
Published: 2006

40. Differential effect of HIV protease inhibitors on adipogenesis: intracellular ritonavir is not sufficient to inhibit differentiation

Author: Vernochet, C., Azoulay, S., Duval, D., Guedj, R., Cottrez, F., Vidal, H., Ailhaud, G., Dani, C., Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Molécules Bioactives et des Arômes (LCMBA), Interactions cellulaires en immunologie et immunopathologie, Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-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)-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), 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), Oillaux, Genevieve, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2005
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41. Extracellular DsbA-insensitive folding of Escherichia coli heat-stable enterotoxin STa in vitro

Author: Isabelle Batisson, Maurice Der Vartanian, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie, Institut National de la Recherche Agronomique (INRA), and Unité de Microbiologie (MIC)
Subjects: Protein Folding, Protein Conformation, Enterotoxin, MESH: Amino Acid Sequence, medicine.disease_cause, Biochemistry, law.invention, MESH: Genotype, Enterotoxins, MESH: Protein Conformation, law, Amino Acid Sequence, Bacterial Proteins, Bacterial Toxins, Cloning, Molecular, Disulfides, Escherichia coli, Genotype, Humans, Membrane Proteins, Molecular Sequence Data, Phenotype, Protein Disulfide-Isomerases, Recombinant Fusion Proteins, MESH: Enterotoxins, Heat-stable enterotoxin, Cloning, Molecular, MESH: Bacterial Proteins, 0303 health sciences, biology, MESH: Escherichia coli, Escherichia coli Proteins, Microbiology and Parasitology, Microbiologie et Parasitologie, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Recombinant DNA, MESH: Membrane Proteins, Signal peptide, MESH: Protein Folding, MESH: Phenotype, 03 medical and health sciences, medicine, SDV:BBM, MESH: Recombinant Fusion Proteins, MESH: Protein Disulfide-Isomerases, Secretion, MESH: Cloning, Molecular, MESH: Disulfides, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, 030306 microbiology, Cell Biology, Periplasmic space, DsbA, MESH: Bacterial Toxins, biology.protein
Abstract: International audience; To study the folding of human Escherichia coli heat-stable enterotoxin STh, we used the major protein subunit of CS31A fimbriae (ClpG) as a marker of STh secretion and a provider of a signal peptide. We established that STh genetically fused to the N or C terminus of ClpG was able to mobilize ClpG to the culture supernatant while still retaining full enterotoxicity. These features indicate that the STh activity was not altered by the chimeric structure and suggest that spatial conformation of STh in the fusion is close to that of the native toxin, thus permitting recognition and activation of the intestinal STh receptor in vivo. In contrast to other studies, we showed that disulfide bond formation did not occur in the periplasm through the DsbA pathway and that there was no correlation between DsbA and secretion, folding, or activity. This discrepancy was not attributable to the chimeric nature of STh since there was no effect of dsbA or dsbB mutations on secretion and activity of recombinant STh from which ClpG had been deleted. Periplasmic and lysate fractions of dsbA(+) and dsbA(-) cells did not have any STh activity. In addition, the STh chimera was exclusively found in an inactive reduced form intracellularly and in an active oxidized form extracellularly, irrespective of the dsbA background. Subsequently, a time course experiment in regard to the secretion of STh from both dsbA(+) and dsbA(-) cells indicated that the enterotoxin activity (proper folding) in the extracellular milieu increased with time. Overall, these findings provide evidence that STa toxins can be cell-released in an unfolded state before being completely disulfide-bonded outside the cell.
Published: 2000

42. Mécanismes de la perception gustative des lipides alimentaires

Author: Philippe Besnard, Dany Gaillard, Patricia Passilly-Degrace, Naim Akhtar Khan, Aziz Hichami, and Abdelghani El-Yassimi
Subjects: Philosophy, SDV:BBM, Gustatory system, General Medicine, Long chain, Humanities, General Biochemistry, Genetics and Molecular Biology
Abstract: > L’obesite constitue indeniablement un des problemes majeurs de sante publique de ce debut du XXIe siecle. Sa prevalence est en constante augmentation notamment chez les enfants. Ce constat n’est pas anodin car l’obesite est souvent associee a diverses pathologies graves (atteintes vasculaires, diabete de type 2, hypertension, cancer). L’opulence alimentaire, en nous permettant de satisfaire nos appetits specifiques, contribue a ce phenomene. C’est ainsi que dans le regime occidental, les lipides alimentaires representent pres de 40 % des apports caloriques journaliers alors que les recommandations nutritionnelles sont inferieures de 5 a 10 %. L’origine de cette attirance pour les corps gras, encore mal connue, est egalement observee chez la souris. Dans cette espece, on a longtemps pense que la perception oro-sensorielle des lipides alimentaires dependait uniquement de leurs proprietes olfactives et texturales. Cette vision quelque peu restrictive a recemment ete battue en breche par une serie d’experiences montrant que la gustation joue egalement un role important dans la preference spontanee pour les corps gras.
Published: 2008
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43. Understanding the regulation of aspartate metabolism using a model based on measured kinetic parameters

Author: Olivier Bastien, Athel Cornish-Bowden, Renaud Dumas, Mylène Robert-Genthon, María Luz Cárdenas, Gilles Curien, Laboratoire de physiologie cellulaire végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Chloroplasts, Arabidopsis thaliana, Arabidopsis, Aspartate metabolism, plant, 01 natural sciences, enzyme kinetics, Threonine, Amino Acids, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, aspartate, Mathematical model, Applied Mathematics, simulation, Recombinant Proteins, Computational Theory and Mathematics, Biochemistry, General Agricultural and Biological Sciences, Biological system, aminoacid, flux distribution, Information Systems, metabolism, metabolic pathway, mathematical model, allosteric regulation, threonine, Allosteric regulation, Biology, Kinetic energy, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, aspartate metabolism, SDV:BBM, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Computer Simulation, 030304 developmental biology, Aspartic Acid, General Immunology and Microbiology, Kinetic model, Reproducibility of Results, biology.organism_classification, Kinetics, Function (biology), 010606 plant biology & botany
Abstract: International audience; The aspartate-derived amino-acid pathway from plants is well suited for analysing the function of the allosteric network of interactions in branched pathways. For this purpose, a detailed kinetic model of the system in the plant model Arabidopsis was constructed on the basis of in vitro kinetic measurements. The data, assembled into a mathematical model, reproduce in vivo measurements and also provide non-intuitive predictions. A crucial result is the identification of allosteric interactions whose function is not to couple demand and supply but to maintain a high independence between fluxes in competing pathways. In addition, the model shows that enzyme isoforms are not functionally redundant, because they contribute unequally to the flux and its regulation. Another result is the identification of the threonine concentration as the most sensitive variable in the system, suggesting a regulatory role for threonine at a higher level of integration.
Published: 2009
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44. Genetic Evidence for a Link Between Glycolysis and DNA Replication

Author: Laurent Jannière, Danielle Canceill, Catherine Suski, Sophie Kanga, Bérengère Dalmais, Roxane Lestini, Anne-Françoise Monnier, Jérôme Chapuis, Alexander Bolotin, Marina Titok, Emmanuelle Le Chatelier, S. Dusko Ehrlich, 1Génétique Microbienne, INRA, Domaine de Vilvert, 78352 Jouy en Josas Cedex, Institut National de la Recherche Agronomique (INRA), Régulation de l'expression génétique chez les microorganismes (REGCM), Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), laboratoire de Virologie Immunologie Moléculaire, INRA, Jouy, and Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892))
Subjects: DNA Replication, dnaE, Science, Biology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, SDV:BBM, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Viability assay, Gene, Molecular Biology/DNA Replication, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Mutation, Multidisciplinary, DNA synthesis, 030306 microbiology, Microbiology and Parasitology, DNA replication, SDV:GEN, Microbiologie et Parasitologie, Genetics and Genomics/Chromosome Biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Biochemistry, Genes, Bacterial, Medicine, Microbiology/Microbial Physiology and Metabolism, Primase, Glycolysis, DNA, Research Article, Bacillus subtilis
Abstract: BackgroundA challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions.Methodology/principal findingsWe report here a tight link between glycolysis and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of glycolysis. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses.Conclusions/significanceOur findings provide the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous.
Published: 2007
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