Descriptor: "MESH : Gene Expression Profiling" - Searchworks@Jio Institute Digital Library Search Results

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54 results on '"MESH : Gene Expression Profiling"'

1. Comparative Transcriptomic Analysis of Salt Adaptation in Roots of Contrasting Medicago truncatula Genotypes

Author: Véronique Gruber, Jean-Laurent Ichanté, Axel de Zélicourt, Laura de Lorenzo, Benoit Alunni, Sandrine Imbeaud, Hervé Delacroix, Sandrine Blanchet, Carole Laffont, Mounawer Badri, Anouck Diet, Julie Plet, Esther M. González, Florian Frugier, Ons Zahaf, Martin Crespi, Ana Zabalza, 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 des sciences du végétal (ISV), Centre National de la Recherche Scientifique (CNRS), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11), 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 des sciences du végétal ( ISV ), Centre National de la Recherche Scientifique ( CNRS ), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de génétique moléculaire ( CGM ), and Université Paris-Sud - Paris 11 ( UP11 )
Subjects: 0106 biological sciences, [ SDV.BV ] Life Sciences [q-bio]/Vegetal Biology, MESH : Molecular Sequence Data, MESH : Plant Roots, MESH: Plant Roots, MESH : Genotype, Plant Science, Sodium Chloride, 01 natural sciences, Plant Roots, Transcriptome, MESH: Genotype, Gene Expression Regulation, Plant, MESH: Medicago truncatula, MESH : Adaptation, Physiological, Plant Proteins, 2. Zero hunger, Abiotic component, chemistry.chemical_classification, 0303 health sciences, MESH: Plant Proteins, food and beverages, Adaptation, Physiological, Medicago truncatula, MESH : Sodium Chloride, Soil salinity, MESH: Sodium Chloride, Genotype, Molecular Sequence Data, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, Auxin, MESH : Plant Proteins, Botany, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MESH: Gene Expression Regulation, Plant, Gene, Molecular Biology, 030304 developmental biology, MESH: Molecular Sequence Data, Abiotic stress, MESH : Gene Expression Profiling, MESH : Medicago truncatula, Gene Expression Profiling, fungi, 15. Life on land, biology.organism_classification, MESH: Adaptation, Physiological, chemistry, Adaptation, MESH : Gene Expression Regulation, Plant, 010606 plant biology & botany
Abstract: International audience; Evolutionary diversity can be driven by the interaction of plants with different environments. Molecular bases involved in ecological adaptations to abiotic constraints can be explored using genomic tools. Legumes are major crops worldwide and soil salinity is a main stress affecting yield in these plants. We analyzed in the Medicago truncatula legume the root transcriptome of two genotypes having contrasting responses to salt stress: TN1.11, sampled in a salty Tunisian soil, and the reference Jemalong A17 genotype. TN1.11 plants show increased root growth under salt stress as well as a differential accumulation of sodium ions when compared to A17. Transcriptomic analysis revealed specific gene clusters preferentially regulated by salt in root apices of TN1.11, notably those related to the auxin pathway and to changes in histone variant isoforms. Many genes encoding transcription factors (TFs) were also differentially regulated between the two genotypes in response to salt. Among those selected for functional studies, overexpression in roots of the A17 genotype of the bHLH-type TF most differentially regulated between genotypes improved significantly root growth under salt stress. Despite the global complexity of the differential transcriptional responses, we propose that an increase in this bHLH TF expression may be linked to the adaptation of M. truncatula to saline soil environments.
Published: 2012
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2. Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFβ signaling pathways

Author: Hélène Gilgenkrantz, Cédric Coulouarn, Sébastien Jacques, Anne Audebourg, Catherine Cavard, Florent Dumont, Christine Perret, Pierre-Alexandre Just, Bruno Clément, Benoit Terris, Laura Rubbia-Brandt, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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), Microenvironnement et remodelage, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: MESH: Signal Transduction, Cancer Research, Pathology, MESH : Liver Neoplasms, Cellular differentiation, MESH: beta Catenin, ddc:616.07, Cholangiocarcinoma/etiology/pathology, Cholangiocarcinoma, 0302 clinical medicine, Transforming Growth Factor beta, MESH: Liver Neoplasms, MESH: Carcinoma, Hepatocellular, Wnt Signaling Pathway, beta Catenin, Hepatocyte differentiation, MESH : Prognosis, Tissue microarray, Neoplastic Stem Cells/pathology, Liver Neoplasms, MESH : Extracellular Matrix, MESH: Wnt Signaling Pathway, Wnt signaling pathway, Cell Differentiation, General Medicine, Prognosis, Extracellular Matrix, 3. Good health, Transforming Growth Factor beta/physiology, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030211 gastroenterology & hepatology, Wnt Signaling Pathway/physiology, Stem cell, MESH: Tissue Array Analysis, MESH : Cell Differentiation, Signal Transduction, MESH : Carcinoma, Hepatocellular, MESH: Cell Differentiation, medicine.medical_specialty, Carcinoma, Hepatocellular, MESH : Wnt Signaling Pathway, Beta Catenin/physiology, MESH: Extracellular Matrix, Biology, MESH: Prognosis, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : Neoplastic Stem Cells, medicine, Extracellular Matrix/physiology, Humans, Progenitor cell, MESH: Transforming Growth Factor beta, Progenitor, MESH : Signal Transduction, MESH: Humans, Carcinoma, Hepatocellular/etiology/pathology, Signal Transduction/physiology, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, Liver Neoplasms/etiology/pathology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Cholangiocarcinoma, MESH : beta Catenin, MESH: Cholangiocarcinoma, MESH: Neoplastic Stem Cells, Gene expression profiling, Bile Ducts, Intrahepatic, MESH : Transforming Growth Factor beta, Bile Duct Neoplasms, Tissue Array Analysis, MESH : Tissue Array Analysis
Abstract: International audience; Intrahepatic malignant tumours include hepatocellular carcinomas (HCC), cholangiocarcinomas (CC) and combined hepatocholangiocarcinomas (cHCC-CC), a group of rare and poorly characterized tumours that exhibit both biliary and hepatocytic differentiation. The aim of the study was to characterize the molecular pathways specifically associated with cHCC-CC pathogenesis. We performed a genome-wide transcriptional analysis of 20 histologically defined cHCC-CC and compared them with a series of typical HCC and of CC. Data were analysed by gene set enrichment and integrative genomics and results were further validated in situ by tissue microarray using an independent series of 152 tumours. We report that cHCC-CC exhibit stem/progenitor features, a down-regulation of the hepatocyte differentiation program and a commitment to the biliary lineage. TGFβ and Wnt/β-catenin were identified as the two major signalling pathways activated in cHCC-CC. A β-catenin signature distinct from that observed in well-differentiated HCC with mutant β-catenin was found in cHCC-CC. This signature was associated with microenvironment remodelling and TGFβ activation. Furthermore, integrative genomics revealed that cHCC-CC share characteristics of poorly differentiated HCC with stem cell traits and poor prognosis. The common traits displayed by CC, cHCC-CC and some HCC suggest that these tumours could originate from stem/progenitor cell(s) and raised the hypothesis of a potential continuum between intrahepatic CC, cHCC-CC and poorly differentiated HCC.
Published: 2012
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3. miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

Author: Khalil Arar, Christina Laurini, Michèle Sabbah, Laurent Vallar, Michèle Moes, Charles-Henri Lecellier, Evelyne Friederich, A. Le Bechec, Guillaume Vetter, Anne Saumet, Charles Theillet, Le Ster, Yves, Cytoskeleton and Cell Plasticity Lab, Université du Luxembourg (Uni.lu), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche Publique- Santé, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sigma-Aldrich - Evry GENEPOLE, Sigma-Aldrich, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Fond National de la Recherche (FNR) du Luxembourg, (BIOSAN), the Fondation Luxembourgeoise Contre le Cancer, Human Frontier Science Program (RGP0058/2005), INSERM and CNRS, France. A. Saumet is a recipient of a fellowship from the Ministère de la Culture, de l'Enseignement Supérieur et de la Recherche, Luxembourg (BFR 08/046). M. Moes and A. Le Béchec are supported by AFR grants from the Fond National de la Recherche, Luxembourg., CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université du Luxembourg ( Uni.lu ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: SNAI1, Cancer Research, MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Cell Dedifferentiation, Gene Expression, MESH : Breast Neoplasms, Biochemistry, biophysics & molecular biology [F05] [Life sciences], Validation Studies as Topic, MESH : RNA, Small Interfering, medicine.disease_cause, Bioinformatics, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Metastasis, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Validation Studies as Topic, EMT/miR-661/ SNAI1/StarD10/Nectin-1/breast cancer cell invasion, MESH: RNA, Small Interfering, Tumor Cells, Cultured, MESH : Female, RNA, Small Interfering, Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], Oligonucleotide Array Sequence Analysis, 0303 health sciences, EMT, MESH: Transcription Factors, MESH: Gene Expression Regulation, Neoplastic, MESH : Epithelial Cells, Gene Expression Regulation, Neoplastic, MESH : Oligonucleotide Array Sequence Analysis, MESH: Epithelial Cells, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, Female, Breast disease, StarD10, Nectin-1, MESH: Gene Expression, MESH : Gene Expression Regulation, Neoplastic, Nectins, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, MESH : Cell Adhesion Molecules, MESH: Gene Expression Profiling, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, Genetics, medicine, Humans, Gene silencing, Neoplasm Invasiveness, RNA, Messenger, MESH: Tumor Cells, Cultured, Epithelial–mesenchymal transition, Molecular Biology, MESH: RNA, Messenger, 030304 developmental biology, breast cancer cell invasion, MESH: Validation Studies as Topic, MESH: Humans, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, Cancer, Epithelial Cells, Mesenchymal Stem Cells, MESH: Neoplasm Invasiveness, Cell Dedifferentiation, Phosphoproteins, medicine.disease, MESH: Cell Dedifferentiation, miR-661, MESH : Gene Expression, MESH : MicroRNAs, MicroRNAs, Retraction Note, MESH: Mesenchymal Stem Cells, MESH: Oligonucleotide Array Sequence Analysis, Cancer research, Snail Family Transcription Factors, MESH : Phosphoproteins, MESH : Mesenchymal Stem Cells, Carcinogenesis, Cell Adhesion Molecules, MESH: MicroRNAs, MESH: Female, MESH: Breast Neoplasms, Transcription Factors
Abstract: 4; International audience; Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3'-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.
Published: 2010
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4. EFD Is an ERF Transcription Factor Involved in the Control of Nodule Number and Differentiation inMedicago truncatula

Author: Françoise de Billy, Andreas Niebel, Tatiana Vernié, Christian Rogers, Florian Frugier, Giles E. D. Oldroyd, Julie Plet, Jean-Philippe Combier, Pascal Gamas, Sandra Moreau, Laboratoire des interactions plantes micro-organismes ( LIPMO ), Institut National de la Recherche Agronomique ( INRA ) -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 ), Institut des sciences du végétal ( ISV ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des interactions plantes micro-organismes (LIPM), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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), Institut des sciences du végétal (ISV), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: MESH: Signal Transduction, 0106 biological sciences, [ SDV.BV ] Life Sciences [q-bio]/Vegetal Biology, Cytokinins, MESH : Molecular Sequence Data, MESH : Transcription Factors, MESH: Feedback, Physiological, Regulator, MESH : Gene Deletion, Plant Science, Plant Root Nodulation, 01 natural sciences, Nod factor, chemistry.chemical_compound, MESH : Nitrogen Fixation, MESH: Phylogeny, MESH: Medicago truncatula, Research Articles, Phylogeny, Plant Proteins, Regulator gene, Feedback, Physiological, MESH : Cell Nucleus, 0303 health sciences, MESH: Plant Proteins, food and beverages, MESH: Transcription Factors, MESH : Feedback, Physiological, MESH : Cytokinins, Medicago truncatula, Cell biology, MESH: Root Nodules, Plant, Multigene Family, Cytokinin, RNA Interference, MESH: Cytokinins, Root Nodules, Plant, MESH: Plant Root Nodulation, Signal Transduction, MESH: Cell Nucleus, MESH: Ethylenes, Molecular Sequence Data, MESH: RNA Interference, MESH : Multigene Family, Biology, MESH: Nitrogen Fixation, MESH: Gene Expression Profiling, MESH : Root Nodules, Plant, 03 medical and health sciences, Nitrogen Fixation, MESH : Plant Proteins, Botany, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Transcription factor, 030304 developmental biology, Cell Nucleus, MESH : Signal Transduction, MESH: Molecular Sequence Data, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Medicago truncatula, fungi, MESH : Phylogeny, MESH : Sinorhizobium meliloti, Cell Biology, Ethylenes, Meristem, biology.organism_classification, Response regulator, chemistry, MESH: Gene Deletion, MESH: Multigene Family, MESH : RNA Interference, MESH: Sinorhizobium meliloti, MESH : Plant Root Nodulation, Gene Deletion, MESH : Ethylenes, Sinorhizobium meliloti, Transcription Factors, 010606 plant biology & botany
Abstract: Mechanisms regulating legume root nodule development are still poorly understood, and very few regulatory genes have been cloned and characterized. Here, we describe EFD (for ethylene response factor required for nodule differentiation), a gene that is upregulated during nodulation in Medicago truncatula. The EFD transcription factor belongs to the ethylene response factor (ERF) group V, which contains ERN1, 2, and 3, three ERFs involved in Nod factor signaling. The role of EFD in the regulation of nodulation was examined through the characterization of a null deletion mutant (efd-1), RNA interference, and overexpression studies. These studies revealed that EFD is a negative regulator of root nodulation and infection by Rhizobium and that EFD is required for the formation of functional nitrogen-fixing nodules. EFD appears to be involved in the plant and bacteroid differentiation processes taking place beneath the nodule meristem. We also showed that EFD activated Mt RR4, a cytokinin primary response gene that encodes a type-A response regulator. We propose that EFD induction of Mt RR4 leads to the inhibition of cytokinin signaling, with two consequences: the suppression of new nodule initiation and the activation of differentiation as cells leave the nodule meristem. Our work thus reveals a key regulator linking early and late stages of nodulation and suggests that the regulation of the cytokinin pathway is important both for nodule initiation and development.
Published: 2008
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5. The strong induction of metallothionein gene following cadmium exposure transiently affects the expression of many genes in Eisenia fetida: A trade-off mechanism?

Author: Sébastien Lemière, R. Leroux, F. Brulle, Alain Leprêtre, Guillaume Mitta, Franck Vandenbulcke, Laboratoire d'Ecologie Numérique et d'Ecotoxicologie, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Parasitologie fonctionnelle et évolutive [2003-2006] (PFE), Centre National de la Recherche Scientifique (CNRS)-Université de Perpignan Via Domitia (UPVD), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée (DAPNIA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique ( CNRS ), Parasitologie fonctionnelle et évolutive ( PFE ), Université de Perpignan Via Domitia ( UPVD ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Astrophysique, de physique des Particules, de physique Nucléaire et de l'Instrumentation Associée ( DAPNIA ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), and Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : RNA, Messenger, Physiology, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Toxicology, 01 natural sciences, Biochemistry, MESH : Soil Pollutants, Soil Pollutants, Metallothionein, MESH: Animals, MESH : Copper, MESH : Cadmium, Regulation of gene expression, 0303 health sciences, MESH : Gene Expression Regulation, Effector, MESH: Cyclophilin A, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: Oligochaeta, General Medicine, MESH: Gene Expression Regulation, MESH: Copper, [ SDV.BID.EVO ] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH : Oligochaeta, Cyclophilin A, Cadmium, Eisenia fetida, MESH: Cadmium, MESH : Cyclophilin A, Biology, Superoxide dismutase, MESH: Gene Expression Profiling, 03 medical and health sciences, Heat shock protein, Animals, RNA, Messenger, Oligochaeta, Protein kinase C, MESH: RNA, Messenger, 030304 developmental biology, 0105 earth and related environmental sciences, MESH: Soil Pollutants, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Metallothionein, MESH: Biological Markers, Cell Biology, biology.organism_classification, MESH : Metallothionein, MESH : Biological Markers, Gene expression profiling, Gene Expression Regulation, 13. Climate action, biology.protein, MESH : Animals, Biomarkers, Copper
Abstract: Metal pollution causes disturbances at various levels of biological organization in most species. Important physiological functions could be affected in the exposed individuals and among the main physiological functions, immunity may provide one (or more) effector(s) whose expression can be directly affected by a metal exposure in various macroinvertebrates. Protein expressions were studied in order to test them as molecular biomarkers of metal exposure in Eisenia fetida. Selected effectors were calmodulin, heat shock proteins, superoxide dismutase, catalase, metallothionein, beta-adrenergic receptor kinase, pyruvate carboxylase, transcriptionally controlled tumor protein, protein kinase C, ubiquitin and cyclophilin-A. The level of expression of each gene was analysed in whole organism following exposures to cadmium in soil using real-time PCR. Metallothionein, transcriptionally controlled tumor protein and cyclophilin-A expression were also measured following copper exposures in soil because these genes seemed to be sensitive to copper. This work enabled to distinguish metallothionein and cyclophilin-A among the 15 selected effectors. A strong decrease of the number of transcripts was also detected for most effectors soon after the exposure to cadmium suggesting that a trade-off mechanism occurs.
Published: 2007
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6. Expression colique de l’interféron-γ et de l’interleukine-10 au cours de la maladie de Crohn et de la rectocolite ulcéro-hémorragique

Author: A. Sassi, Lamia Kallel, M. Ben Ahmed, Samir Boubaker, Hechmi Louzir, Béchir Zouari, Azza Filali, Jalel Boubaker, Service de gastroentérologie A, Hôpital de La Rabta Tunis, Laboratoire de Transmission, Contrôle et Immunobiologie des Infections ( LR11IPT02 ), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Institut Pasteur de Tunis, Département de médecine préventive et de statistiques, Faculté de Médecine de Tunis, Hôpital La Rabta [Tunis], Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Réseau International des Instituts Pasteur (RIIP)
Subjects: MESH: Interleukin-10, MESH : RNA, Messenger, [SDV]Life Sciences [q-bio], MESH: Down-Regulation, MESH : Down-Regulation, MESH: Biopsy, 0302 clinical medicine, MESH : Child, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Child, Gamma interferon, Medicine, MESH : Female, MESH : Colonoscopy, 0303 health sciences, MESH: Middle Aged, MESH : Immunity, Mucosal, MESH : RNA, Ribosomal, MESH : Reverse Transcriptase Polymerase Chain Reaction, General Medicine, MESH : Adult, MESH : Colitis, Ulcerative, MESH: Case-Control Studies, MESH: Colonoscopy, MESH: Intestinal Mucosa, MESH : Severity of Illness Index, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030211 gastroenterology & hepatology, MESH : Case-Control Studies, MESH: Gene Expression, MESH: Interferon-gamma, MESH : Male, MESH: Colitis, Ulcerative, MESH : Crohn Disease, MESH : Intestinal Mucosa, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH: Severity of Illness Index, MESH : Adolescent, MESH : Interleukin-10, MESH : Middle Aged, MESH: Colon, MESH : Interferon-gamma, MESH: RNA, Messenger, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Crohn Disease, [ SDV ] Life Sciences [q-bio], Crohn disease, business.industry, MESH: Transcription, Genetic, MESH : Gene Expression Profiling, MESH : Humans, MESH : Transcription, Genetic, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Colon, Molecular biology, MESH: Male, MESH : Gene Expression, MESH: Immunity, Mucosal, MESH : Biopsy, MESH: RNA, Ribosomal, business, MESH: Female
Abstract: Resume Objectif Le but de ce travail etait d’explorer l’expression colique de l’INF-γ et de l’IL-10 chez des patients atteints de maladie de Crohn (MC) ou de rectocolite ulcero-hemorragique (RCH). Methodes Quatorze patients atteints de MC et 11 atteints de RCH ont ete inclus, ainsi que 7 sujets temoins. L’etude de l’expression colique de l’INF-γ et de l’IL-10 a ete realisee sur des biopsies de colon sain et malade, en utilisant la technique de transcription inverse et d’amplification genique (RT-PCR) en temps reel (Taqman). Les resultats ont ete exprimes sous forme de rapport entre la quantite d’ARN messager (ARNm) de la cytokine et celle d’une molecule de reference, l’ARN ribosomal 18S, puis multiplie par 10 8 . Resultats En cas de maladie de Crohn, le colon exprimait plus d’INF-γ et d’IL-10 par rapport aux temoins (medianes respectives : 23,03 vs 1,87, p = 0,042 et 20,61 vs 2,13, p = 0,08). Une puissante correlation positive a ete trouvee entre l’expression colique de l’IL-10 et celle de l’INF-γ au cours de la MC (r = 0,9, p Au niveau des sites lesionnels de RCH, l’expression de l’INF-γ ainsi que celle de l’IL-10 etaient comparables a celles observees chez les temoins (7,18 vs 2,18, p = 0,36 et 3,66 vs 1,87, p = 0,44). Conclusion Au cours de la maladie de Crohn, l’expression de l’IL-10 et celle de l’INF-γ etaient plus elevees que chez les temoins et etroitement correlees.
Published: 2005
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7. GoArrays: highly dynamic and efficient microarray probe design

Author: Pierre Peyret, David E. Hill, Cécile Militon, Sébastien Rimour, 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 d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), This work was supported by a grant from the CNRS ‘puces à ADN'. S.R. and C.M. were supported by a grant from ‘Ministère de l'éducation, de la recherche et de la technologie'., Technische Hoschschule, University of Applied Sciences [Darmstadt], Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN), Conception, Ingénierie et Développement de l'Aliment et du Médicament (CIDAM), Université d'Auvergne - Clermont-Ferrand I (UdA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes ( LIMOS ), Centre National de la Recherche Scientifique ( CNRS ) -Sigma CLERMONT ( Sigma CLERMONT ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Transcription Factors, probe design, Microarray, MESH: Oligonucleotide Probes, MESH : Equipment Design, Quantitative Biology - Quantitative Methods, Biochemistry, Software, MESH: Animals, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Biopuces ADN, Quantitative Methods (q-bio.QM), MESH : Algorithms, MESH : Encephalitozoon cuniculi, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, biology, Biological modeling, Equipment Design, MESH: Transcription Factors, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH : Oligonucleotide Array Sequence Analysis, Computational Mathematics, Computational Theory and Mathematics, Computer-Aided Design, Software design, MESH : Software, MESH: Encephalitozoon cuniculi, DNA microarray, Encephalitozoon cuniculi, Algorithms, algorithme, Statistics and Probability, MESH : Computer-Aided Design, MESH: Algorithms, Computational biology, génomique, Intracellular pathogen, MESH: Gene Expression Profiling, MESH: Software, 03 medical and health sciences, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Animals, microbiologie, Molecular Biology, 030304 developmental biology, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, 030306 microbiology, Oligonucleotide, business.industry, Gene Expression Profiling, MESH : Gene Expression Profiling, transcriptomique, MESH: Computer-Aided Design, biology.organism_classification, MESH : Oligonucleotide Probes, FOS: Biological sciences, MESH: Oligonucleotide Array Sequence Analysis, MESH : Animals, DNA microarrays, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Oligonucleotide Probes, business, Transcription Factors, MESH: Equipment Design
Abstract: Motivation: The use of oligonucleotide microarray technology requires a very detailed attention to the design of specific probes spotted on the solid phase. These problems are far from being commonplace since they refer to complex physicochemical constraints. Whereas there are more and more publicly available programs for microarray oligonucleotide design, most of them use the same algorithm or criteria to design oligos, with only little variation. Results: We show that classical approaches used in oligo design software may be inefficient under certain experimental conditions, especially when dealing with complex target mixtures. Indeed, our biological model is a human obligate parasite, the microsporidia Encephalitozoon cuniculi. Targets that are extracted from biological samples are composed of a mixture of pathogen transcripts and host cell transcripts. We propose a new approach to design oligonucleotides which combines good specificity with a potentially high sensitivity. This approach is original in the biological point of view as well as in the algorithmic point of view. We also present an experimental validation of this new strategy by comparing results obtained with standard oligos and with our composite oligos. A specific E.cuniculi microarray will overcome the difficulty to discriminate the parasite mRNAs from the host cell mRNAs demonstrating the power of the microarray approach to elucidate the lifestyle of an intracellular pathogen using mix mRNAs. Availability: Our method is implemented in the GoArrays software, available at http://www.isima.fr/bioinfo/goarrays/ Contact: rimour@isima.fr for computing part, and pierre.peyret@univ-bpclermont.fr for collaborative projects.
Published: 2004
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8. Single-cell analysis of thymocyte differentiation: identification of transcription factor interactions and a major stochastic component in αβ-lineage commitment

Author: Sophie Ezine, Benedita Rocha, Serge M. Candéias, Amine Boudil, Agnès Legrand, Lamia Skhiri, Laetitia Gautreau-Rolland, Marie Bedora-Faure, Valérie Pasqualetto, Différenciation et physiologie des lymphocytes T (U1020), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie et Biologie des Métaux ( LCBM - UMR 5249 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Paris Descartes - Paris 5 ( UPD5 ), Différenciation et physiologie des lymphocytes T ( U1020 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique (CNRS)-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), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: MESH : Cell Line, MESH : Transcription Factors, Cellular differentiation, lcsh:Medicine, MESH : Thymocytes, Mice, 0302 clinical medicine, Single-cell analysis, Gene expression, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, lcsh:Science, 0303 health sciences, Multidisciplinary, Thymocytes, GATA3, Cell Differentiation, MESH: Transcription Factors, medicine.anatomical_structure, MESH : Single-Cell Analysis, MESH: Stochastic Processes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Single-Cell Analysis, MESH : Cell Differentiation, Research Article, MESH: Cell Differentiation, MESH: Thymocytes, T cell, MESH : Cell Lineage, MESH : Stochastic Processes, Biology, Cell Line, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Mice, medicine, Animals, Cell Lineage, Transcription factor, MESH: Mice, 030304 developmental biology, Stochastic Processes, MESH : Gene Expression Profiling, Gene Expression Profiling, lcsh:R, MESH: Cell Lineage, Molecular biology, MESH: Cell Line, Gene expression profiling, Cell culture, lcsh:Q, MESH : Animals, 030215 immunology, Transcription Factors, MESH: Single-Cell Analysis
Abstract: International audience; T cell commitment and $\alpha\beta$/$\gamma\delta$ lineage specification in the thymus involves interactions between many different genes. Characterization of these interactions thus requires a multiparameter analysis of individual thymocytes. We developed two efficient single-cell methods: (i) the quantitative evaluation of the co-expression levels of nine different genes, with a plating efficiency of 99-100% and a detection limit of 2 mRNA molecules/cell; and (ii) single-cell differentiation cultures, in the presence of OP9 cells transfected with the thymus Notch1 ligand DeltaL4. We show that during T cell commitment, Gata3 has a fundamental, dose-dependent role in maintaining Notch1 expression, with thymocytes becoming T-cell-committed when they co-express Notch1, Gata3 and Bc11b. Of the transcription factor expression patterns studied here, only that of Bcl11b was suggestive of a role in Pu1 down-regulation. Individual thymocytes became $\alpha\beta$$\gamma\delta$-lineage-committed at very different stages (from the TN2a stage onwards). However, 20% of TN3 cells are not $\alpha\beta$/$\gamma\delta$ lineage committed and TN4 cells comprise two main subpopulations with different degrees of maturity. The existence of a correlation between differentiation potential and expression of the pre-TCR showed that 83% of $\alpha\beta$-committed cells do not express the pre-TCR and revealed a major stochastic component in $\alpha\beta$-lineage specification.
Published: 2013
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9. Investigation of secreted protein transcripts as early biomarkers for type 1 diabetes in the mouse model

Author: Edouard Yeramian, Fredj Tekaia, Evie Melanitou, Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur [Paris], Génétique Moléculaire des Levures, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bioinformatique Structurale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), FT acknowledges financial support from the Institut Pasteur (PTR 370)., EM thanks Dr. Geneviève Milon for constant support and encouraging discussions., Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunophysiologie et Parasitisme, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and EM thanks Dr. Geneviève Milon for constant support and encour- aging discussions.FT acknowledges financial support from the Institut Pasteur (PTR 370).
Subjects: MESH: Mice, Inbred NOD, MESH : Transcriptome, Autoimmunity, Disease, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, Bioinformatics, Transcriptome, MESH : Diabetes Mellitus, Type 1, Mice, 0302 clinical medicine, Mice, Inbred NOD, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cluster Analysis, MESH: Animals, MESH : Biomarkers, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Secretome, 0303 health sciences, MESH : Gene Expression Regulation, Diabetes, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Gene Expression Regulation, Transmembrane protein, Correspondence analysis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Pancreas, MESH: Diabetes Mellitus, Type 1, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Mice, Genetics, medicine, MESH : Cluster Analysis, Animals, Humans, Gene, MESH: Mice, 030304 developmental biology, Type 1 diabetes, MESH: Humans, MESH : Mice, Inbred NOD, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH: Transcriptome, MESH : Humans, Autoantibody, medicine.disease, MESH : Disease Models, Animal, MESH: Cluster Analysis, Disease Models, Animal, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Diabetes Mellitus, Type 1, Gene Expression Regulation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Immunology, MESH: Biomarkers, MESH : Animals, MESH: Disease Models, Animal, Biomarkers
Abstract: International audience; Type 1 diabetes (T1D) represents a serious health burden in the world, complicated by the fact that disease onset can be preceded by a long time period without evident clinical signs. It would be then of critical importance to detect the disease in its early stages. In this direction, we seek here to identify early preinflammatory markers for autoimmune diabetes, mining our previously reported transcriptome data relevant to distinct early sub-phenotypes in the NOD mouse, associated with early insulin autoantibodies (E-IAA). More specifically we focus on secreted or transmembrane protein transcripts, identifying in this category 71 differentially expressed transcripts which are regulated at the early preinflammatory stages of T1D in the pancreatic lymph nodes (PLN). Following the expression patterns of these 71 transcripts, correspondence analysis (a multivariate analysis method) reveals a clear-cut segregation of the individual samples according to the early subphenotype used. Thus the 71 transcripts coding for secreted proteins constitute a candidate-set of predictive biomarkers for the development of autoimmune damage of the β cells of the pancreas. The majority of these genes have human orthologs and accordingly they represent potential candidate biomarkers for the human disease. In addition, for predictive purposes, the analysis reveals the possibility to reduce significantly the size of the candidate-set in practice, with various genes displaying identical expression profiles.
Published: 2013
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10. Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma cell motility, associated with metastasis

Author: B. Duthey, François Bertucci, David Jérémie Birnbaum, Thérèse Gargi, Danièle Salaün, Ali Badache, Olivier Tredan, Pascal Finetti, Nathalie Bendriss-Vermare, J. Gillibert-Duplantier, Vanja Sisirak, Le myofibroblaste hépatique : différenciation, rôles physiopathologiques, apoptose, Institut National de la Santé et de la Recherche Médicale ( INSERM ), E14, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), E11, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Carcinoma, Cancer Research, Small interfering RNA, MESH : Pleural Neoplasms, MESH: Matrix Metalloproteinases, Receptor, ErbB-2, MESH : Receptors, Cell Surface, MESH : Breast Neoplasms, MESH : RNA, Small Interfering, Receptor tyrosine kinase, Metastasis, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Receptor, erbB-2, Cell Movement, MESH: RNA, Small Interfering, MESH: Up-Regulation, MESH: Peritoneal Neoplasms, MESH : Cell Movement, RNA, Small Interfering, skin and connective tissue diseases, MESH: Cell Movement, MESH : Up-Regulation, Peritoneal Neoplasms, MESH: Receptors, Cell Surface, 0303 health sciences, Gene knockdown, biology, MESH : Carcinoma, MESH: Gene Expression Regulation, Neoplastic, Metastatic breast cancer, 3. Good health, Cell biology, Up-Regulation, Gene Expression Regulation, Neoplastic, MESH: Receptor, erbB-2, 030220 oncology & carcinogenesis, MESH: Cell Line, Tumor, MESH : Gene Expression Regulation, Neoplastic, Pleural Neoplasms, Motility, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Receptors, Cell Surface, MESH: Pleural Neoplasms, MESH : Matrix Metalloproteinases, 03 medical and health sciences, MESH: Gene Expression Profiling, Breast cancer, MESH : Peritoneal Neoplasms, Cell Line, Tumor, MESH: Antibodies, Blocking, Genetics, medicine, Humans, Antibodies, Blocking, Molecular Biology, neoplasms, 030304 developmental biology, MESH: Humans, MESH : Antibodies, Blocking, MESH : Cell Line, Tumor, Gene Expression Profiling, MESH : Gene Expression Profiling, Carcinoma, MESH : Humans, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Matrix Metalloproteinases, Cell culture, biology.protein, MESH: Breast Neoplasms
Abstract: International audience; Overexpression of the ErbB2 receptor tyrosine kinase in breast cancer contributes to tumor development and is associated with poor prognosis. However, the mechanism by which ErbB2 might contribute to metastasis is not well defined. To identify genes that mediate ErbB2-driven cell motility, we performed differential gene expression analysis of ErbB2-expressing migrating breast cancer cells vs mutant ErbB2-expressing non-migrating cells. Among the genes that were specifically induced in migrating cells were known transcriptional targets of ErbB2, such as matrix metalloproteinases, and novel ErbB2 targets. Contribution of selected candidate genes to ErbB2-driven cell motility was tested by small interfering RNA targeting. Knockdown of the soluble form of ST2 (sST2), also called interleukin-1 receptor-like 1, one of the most robustly induced genes, decreased ErbB2-induced cell motility in two different cell lines. In response to ErbB2 activation, sST2 protein expression and secretion were increased. Moreover, recombinant sST2 associated with the plasma membrane and sST2-blocking antibodies reduced ErbB2-induced motility. Interestingly, cells from metastatic breast tumors secreted higher levels of sST2 than primary tumor cells. Finally, sST2 was found at high levels in the serum of metastatic breast cancer patients. Our data suggest that sST2 contributes to breast cancer cell motility and that sST2 secretion is associated with metastasis.
Published: 2012
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11. A cell-contact-regulated operon is involved in genetic variability in Neisseria meningitidis

Author: Xavier Nassif, Eric Frapy, Dominique Schneider, Anne Jamet, Patricia Martin, Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Universite Paris Descartes, INSERM, Region Ile-De-France, Foundation pour la Recherche Medicale, Centre Régional de Pharmacovigilance ( CRPV ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Operon, Operon, TOPOISOMERASES, Cell, Neisseria meningitidis, medicine.disease_cause, Bacterial Adhesion, MESH : Host-Pathogen Interactions, Genetics, 0303 health sciences, Mutation, MESH: Gene Expression Regulation, Bacterial, SEROGROUP-A, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], General Medicine, GENOME, [ SDV.BID.EVO ] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine.anatomical_structure, Interaction with host, Meningococcus, ESCHERICHIA-COLI, Host-Pathogen Interactions, MESH : Gene Expression Regulation, Bacterial, MESH: Operon, PHASE VARIATION, OUTER-MEMBRANE PROTEIN, MESH : Bacterial Adhesion, Biology, Microbiology, MESH: Neisseria meningitidis, 03 medical and health sciences, MESH: Gene Expression Profiling, Downregulation and upregulation, medicine, HIGH MUTATION-RATES, Humans, Genetic variability, MESH: Bacterial Adhesion, Molecular Biology, Gene, 030304 developmental biology, MESH: Humans, MESH : Neisseria meningitidis, 030306 microbiology, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH: Host-Pathogen Interactions, Gene Expression Regulation, Bacterial, EVOLUTION, bacteria, HOST-CELLS, SYSTEM
Abstract: International audience; The ability of Neisseria meningitidis to establish efficient interaction with host cells is crucial for its survival. We recently demonstrated that an entire operon containing genes NMA1802 to NMA1806 was overexpressed during the early stage of the colonization process. In this work, we investigated whether upregulation of the expression of this operon facilitated the ability of N. meningitidis to adapt to growth on host cells. Using a strain displaying an inducible operon, we demonstrated that the NMA1802-NMA1806 cell-contact-regulated operon could potentially improve the adaptability of meningococcus during growth on the cell surface through enhanced generation of variants.
Published: 2012
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12. TranscriptomeBrowser 3.0 : introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks

Author: Narayanan B. Perumal, Jean Imbert, Cyrille Lepoivre, Denis Puthier, Fabrice Lopez, Aurélie Bergon, Catherine Nguyen, Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Transcriptomic Genomic Marseille-Luminy (TGML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Translational Science, Eli Lilly and Company, Ecole Supérieure d'Ingénieurs de Luminy (ESIL), Université de la Méditerranée - Aix-Marseille 2, This work was supported by the Institut National de la Santé et de la Recherche Médicale (Inserm), the Canceropôle PACA and Marseille-Nice Genopole®. Authors acknowledge financial support from the EU ERASysBio Plus ModHeart project. Fabrice Lopez was supported by a fellowship from the EU STREP grant Diamonds and through funding from the IntegraTCell project (ANR, National Research Agency)., ANR-06-BYOS-0006,IntegraTcells,Analyse et Modélisation Intégrative du Développement des Lymphocytes T(2006), European Project: 32785,ERASYSBIO, BMC, Ed., Biologie systémique (BIOSYS) - Analyse et Modélisation Intégrative du Développement des Lymphocytes T - - IntegraTcells2006 - ANR-06-BYOS-0006 - BIOSYS - VALID, Systems Sciences - ERASYSBIO - 32785 - OLD, Technologies avancées pour le génôme et la clinique ( TAGC ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and ANR-06-BYOS-0006,IntegraTcells,Analyse et Modélisation Intégrative du Développement des Lymphocytes T ( 2006 )
Subjects: Gene regulatory network, Biological database, computer.software_genre, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Proteins, Mice, User-Computer Interface, MESH : Thymocytes, Software, MESH : Dogs, Structural Biology, Databases, Genetic, Gene Regulatory Networks, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], lcsh:QH301-705.5, Oligonucleotide Array Sequence Analysis, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, Thymocytes, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH : Rats, Applied Mathematics, 030302 biochemistry & molecular biology, Cell Differentiation, Genomics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH : Oligonucleotide Array Sequence Analysis, Knowledge base, lcsh:R858-859.7, Graph (abstract data type), [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Data mining, MESH : Software, MESH : Cell Differentiation, Biology, lcsh:Computer applications to medicine. Medical informatics, Set (abstract data type), 03 medical and health sciences, Dogs, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Mice, MESH : User-Computer Interface, Animals, Humans, Plug-in, MESH : Databases, Genetic, Molecular Biology, 030304 developmental biology, business.industry, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Genomics, MESH : Humans, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Proteins, Rats, Visualization, lcsh:Biology (General), MESH : Gene Regulatory Networks, MESH : Animals, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer
Abstract: Background Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. Results We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i) predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices), (ii) potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii) regulatory interactions curated from the literature, (iv) predicted post-transcriptional regulation by micro-RNA, (v) protein kinase-substrate interactions and (vi) physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration of heterogeneous biological information and is a productive avenue in generating new hypotheses. The second objective of InteractomeBrowser is to fill the gap between interaction databases and dynamic modeling. It is thus compatible with the network analysis software Cytoscape and with the Gene Interaction Network simulation software (GINsim). We provide examples underlying the benefits of this visualization tool for large gene set analysis related to thymocyte differentiation. Conclusions The InteractomeBrowser plugin is a powerful tool to get quick access to a knowledge database that includes both predicted and validated molecular interactions. InteractomeBrowser is available through the TranscriptomeBrowser framework and can be found at: http://tagc.univ-mrs.fr/tbrowser/. Our database is updated on a regular basis.
Published: 2012
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13. Aldosterone-producing adenoma formation in the adrenal cortex involves expression of stem/progenitor cell markers

Author: Enzo Lalli, Mathilde Sibony, Xavier Jeunemaitre, Sheerazed Boulkroun, José-Felipe Golib-Dzib, Arndt Benecke, Pierre-François Plouin, Tchao Meatchi, Benoit Samson-Couterie, Maria-Christina Zennaro, Laurence Amar, Estelle Louiset, Hervé Lefebvre, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut des Hautes Etudes Scientifiques (IHES), IHES, Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-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), Université Côte d'Azur (UCA), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, 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), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut des Hautes Etudes Scientifiques ( IHES ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Différenciation et communication neuronale et neuroendocrine ( DC2N ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), UNIROUEN - UFR Santé, Normandie Université ( NU ) -Normandie Université ( NU ), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] ( IRI ), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université Côte d'Azur ( UCA ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Hautes Études Scientifiques (IHES), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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: Aldosterone synthase, MESH: Hypertension, MESH : Adrenal Cortex, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adrenal Glands, MESH : Cell Proliferation, Sonic hedgehog, MESH: Adrenal Glands, Aldosterone, 0303 health sciences, biology, Adrenal cortex, Stem Cells, MESH : Hypertension, medicine.anatomical_structure, Hypertension, MESH : Stem Cells, Zona Glomerulosa, Stem cell, Adenoma, medicine.medical_specialty, MESH: Zona Glomerulosa, education, 030209 endocrinology & metabolism, MESH: Stem Cells, In Vitro Techniques, MESH : Adrenal Glands, 03 medical and health sciences, MESH: Gene Expression Profiling, Zona fasciculata, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, MESH: Cell Proliferation, medicine, Humans, Progenitor cell, Cell Proliferation, 030304 developmental biology, MESH: Adenoma, MESH: Humans, MESH : Aldosterone, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, MESH: Biological Markers, MESH: Aldosterone, MESH : Biological Markers, MESH : Adenoma, chemistry, Zona glomerulosa, Adrenal Cortex, biology.protein, MESH: Adrenal Cortex, MESH : Zona Glomerulosa, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Aldosterone producing adenoma (APA) is the most common form of surgically curable hypertension. To further understand mechanisms involved in APA formation, we investigated the expression of molecules linked to adrenal stem/precursor cells [β-catenin, Sonic hedgehog (Shh), CD56], and nuclear receptors that play key roles in adrenocortical development and function steroidogenic factor 1, dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) in six control adrenal glands and 14 adrenals with APA and compared their expression with that of specific markers of zona glomerulosa (ZG) [CYP11B2, Disabled 2 (Dab2)]. Both Dab2 and CD56 were expressed in ZG. Although Dab2 associates uniquely with differentiated ZG cells and its expression is lost when cells transdifferentiate to zona fasciculata (ZF) cells, CD56 was also expressed in ZF and in aldosterone-producing cell clusters, confirming that these structures possess an intermediate phenotype between ZG and ZF cells. Shh was barely detectable in cells located to the outer part of the ZG in the control adrenal; in contrast, its expression was detected in the entire APA and was dramatically increased in the hyperplastic peritumoral ZG. Transcriptome profiling revealed differential expression of components of Shh signaling pathway in a subgroup of APA. Similarly, Wnt/β-catenin signaling was activated in the majority of APA as well as in the entire peritumoral adrenal cortex; however, no mutation was identified in the CTNNB1 gene that could account for β-catenin activation. Our data suggest that both APA and adjacent ZG present characteristics of stem/precursor cells; the reexpression of genes involved in fetal adrenal development could underlie excessive ZG cell proliferation and APA formation.
Published: 2011
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14. An Expressed Sequence Tag collection from the male antennae of the Noctuid moth Spodoptera littoralis: a resource for olfactory and pheromone detection research

Author: Christelle Monsempes, Fabrice Legeai, Julie Poulain, Marie-Christine François, Christine Merlin, Nicolas Montagné, Frédérick Gavory, Sébastien Malpel, Martine Maïbèche-Coisne, Emmanuelle Jacquin-Joly, François Cousserans, Biologie des organismes et des populations appliquées à la protection des plantes (BIO3P), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Développement et Communication Chimique chez les Insectes (DCCI), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Physiologie de l'Insecte : Signalisation et Communication (PISC), Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-AgroParisTech, Biologie Intégrative et Virologie des Insectes [Univ. de Montpellier II] (BIVI), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), 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), Universite Pierre et Marie Curie (UPMC) ANR-07-NEURO-037-01 ANR-09-BLAN0239-01, Jacquin Joly, Emmanuelle, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), 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 National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biologie des organismes et des populations appliquées à la protection des plantes ( BIO3P ), Institut National de la Recherche Agronomique ( INRA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST, Biological systems and models, bioinformatics and sequences ( SYMBIOSE ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), 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 ), Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Physiologie de l'Insecte : Signalisation et Communication ( PISC ), Institut National de la Recherche Agronomique ( INRA ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -AgroParisTech, Biologie Intégrative et Virologie des Insectes [Univ. de Montpellier II] ( BIVI ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ), Genoscope - Centre national de séquençage [Evry] ( GENOSCOPE ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), 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), and Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, MESH: Sequence Analysis, DNA, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Arthropod Antennae, détection olfactive, MESH : Molecular Sequence Annotation, Genes, Insect, Insect, MESH: Genes, Insect, MESH : Pheromones, Pheromones, 0302 clinical medicine, Arthropod Antennae, Databases, Genetic, MESH: Smell, MESH: Animals, MESH: Phylogeny, Phylogeny, MESH: Databases, Genetic, media_common, Expressed Sequence Tags, 0303 health sciences, Expressed sequence tag, MESH: Pheromones, noctuelle, MESH: Spodoptera, MESH : Expressed Sequence Tags, MESH : Genes, Insect, food and beverages, Smell, Sex pheromone, Pheromone, Biotechnology, Research Article, papillon de nuit, lcsh:QH426-470, MESH : Male, lcsh:Biotechnology, media_common.quotation_subject, Gene prediction, Olfaction, Computational biology, MESH: Molecular Sequence Annotation, Biology, Spodoptera, MESH : Spodoptera, MESH: Expressed Sequence Tags, 03 medical and health sciences, MESH: Gene Expression Profiling, lcsh:TP248.13-248.65, Botany, MESH: Gene Library, Genetics, Animals, MESH : Databases, Genetic, Spodoptera littoralis, 030304 developmental biology, Gene Library, MESH: Arthropod Antennae, MESH : Gene Expression Profiling, Gene Expression Profiling, séquence génomique, fungi, MESH : Phylogeny, Molecular Sequence Annotation, Sequence Analysis, DNA, MESH : Gene Library, biology.organism_classification, MESH: Male, lcsh:Genetics, MESH : Smell, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, MESH : Sequence Analysis, DNA
Abstract: Background Nocturnal insects such as moths are ideal models to study the molecular bases of olfaction that they use, among examples, for the detection of mating partners and host plants. Knowing how an odour generates a neuronal signal in insect antennae is crucial for understanding the physiological bases of olfaction, and also could lead to the identification of original targets for the development of olfactory-based control strategies against herbivorous moth pests. Here, we describe an Expressed Sequence Tag (EST) project to characterize the antennal transcriptome of the noctuid pest model, Spodoptera littoralis, and to identify candidate genes involved in odour/pheromone detection. Results By targeting cDNAs from male antennae, we biased gene discovery towards genes potentially involved in male olfaction, including pheromone reception. A total of 20760 ESTs were obtained from a normalized library and were assembled in 9033 unigenes. 6530 were annotated based on BLAST analyses and gene prediction software identified 6738 ORFs. The unigenes were compared to the Bombyx mori proteome and to ESTs derived from Lepidoptera transcriptome projects. We identified a large number of candidate genes involved in odour and pheromone detection and turnover, including 31 candidate chemosensory receptor genes, but also genes potentially involved in olfactory modulation. Conclusions Our project has generated a large collection of antennal transcripts from a Lepidoptera. The normalization process, allowing enrichment in low abundant genes, proved to be particularly relevant to identify chemosensory receptors in a species for which no genomic data are available. Our results also suggest that olfactory modulation can take place at the level of the antennae itself. These EST resources will be invaluable for exploring the mechanisms of olfaction and pheromone detection in S. littoralis, and for ultimately identifying original targets to fight against moth herbivorous pests.
Published: 2011
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15. Importance of pre-analytical steps for transcriptome and RT-qPCR analyses in the context of the phase II randomised multicentre trial REMAGUS02 of neoadjuvant chemotherapy in breast cancer patients

Author: Véronique Scott, Nicolas Servant, David Gentien, Michel Marty, Philippe Bertheau, Frédérique Spyratos, Patricia de Cremoux, Fabien Valet, Brigitte Sigal-Zafrani, Catherine Barbaroux, Jacqueline Lehmann-Che, Marie-Christine Mathieu, Sophie Vacher, Carine Tran-Perennou, Bernard Asselain, Jean-Marc Guinebretière, BMC, Ed., Département de Biologie des Tumeurs, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biostatistiques, Département de Recherche Translationnelle, Département de biochimie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de recherche translationnelle, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Génétique Oncologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'anatomo-pathologie [Paris], Département de pathologie, Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Centre des Innovations Thérapeutiques en Oncologie et Hématologie, This work was supported by academic grants (PHRC AOM/2OO2/02117) and industrial grants from Pfizer inc., Roche, Sanofi-Aventis.ISRCTN10059974., INSTITUT CURIE, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Département de recherche translationnelle, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut Gustave Roussy ( IGR ), INSTITUT CURIE-Hôpital René HUGUENIN (Saint-Cloud), MINES ParisTech - École nationale supérieure des mines de Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Oncology, Cancer Research, medicine.medical_treatment, quality criteria, MESH : Breast Neoplasms, Bioinformatics, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Transcriptome, 0302 clinical medicine, Reference genes, MESH: Reverse Transcriptase Polymerase Chain Reaction, Cluster Analysis, Medicine, MESH : Female, Neoadjuvant therapy, 0303 health sciences, neoadjuvant setting, Reverse Transcriptase Polymerase Chain Reaction, MESH: Research Design, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Chemotherapy, Adjuvant, MESH: Gene Expression Regulation, Neoplastic, MESH : Research Design, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoadjuvant Therapy, 3. Good health, Gene Expression Regulation, Neoplastic, MESH: Reproducibility of Results, MESH : Antineoplastic Agents, Chemotherapy, Adjuvant, Research Design, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Research Article, medicine.medical_specialty, MESH : Gene Expression Regulation, Neoplastic, MESH: Neoadjuvant Therapy, Antineoplastic Agents, Breast Neoplasms, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, RNA integrity number, lcsh:RC254-282, 03 medical and health sciences, MESH: Gene Expression Profiling, Breast cancer, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Genetics, Humans, MESH : Cluster Analysis, 030304 developmental biology, MESH: Humans, business.industry, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Reproducibility of Results, MESH : Humans, RT-qPCR, Reproducibility of Results, RNA, medicine.disease, MESH: Cluster Analysis, Gene expression profiling, MESH: Antineoplastic Agents, business, MESH : Neoadjuvant Therapy, transcriptome, MESH: Female, MESH: Breast Neoplasms
Abstract: Background Identification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial. Methods This study was conducted on RNA from initial biopsies, in a prospective trial of neoadjuvant chemotherapy in 327 patients with inoperable breast cancer. Four independent centres included patients and samples. Human U133 GeneChips plus 2.0 arrays for transcriptome analysis and quantitative RT-qPCR of 45 target genes and 6 reference genes were analysed on total RNA. Results Thirty seven samples were excluded because i) they contained less than 30% malignant cells, or ii) they provided RNA Integrity Number (RIN) of poor quality. Among the 290 remaining cases, taking into account strict quality control criteria initially defined to ensure good quality of sampling, 78% and 82% samples were eligible for transcriptome and RT-qPCR analyses, respectively. For RT-qPCR, efficiency was corrected by using standard curves for each gene and each plate. It was greater than 90% for all genes. Clustering analysis highlighted relevant breast cancer phenotypes for both techniques (ER+, PR+, HER2+, triple negative). Interestingly, clustering on trancriptome data also demonstrated a "centre effect", probably due to the sampling or extraction methods used in on of the centres. Conversely, the calibration of RT-qPCR analysis led to the centre effect withdrawing, allowing multicentre analysis of gene transcripts with high accuracy. Conclusions Our data showed that strict quality criteria for RNA integrity assessment and well calibrated and standardized RT-qPCR allows multicentre analysis of genes transcripts with high accuracy in the clinical context. More stringent criteria are needed for transcriptome analysis for clinical applications.
Published: 2011
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16. Processing ChIP-chip data: from the scanner to the browser

Author: Cauchy, Pierre, Benoukraf, Touati, Ferrier, Pierre, Technologies avancées pour le génôme et la clinique ( TAGC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Quality Control, Chromatin Immunoprecipitation, Statistics as Topic, MESH : Statistics as Topic, MESH: Quality Control, MESH: Gene Expression Profiling, MESH: Software, MESH : Chromatin Immunoprecipitation, MESH : Coloring Agents, Animals, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Coloring Agents, MESH: Statistics as Topic, Oligonucleotide Array Sequence Analysis, Repetitive Sequences, Nucleic Acid, MESH: Chromatin Immunoprecipitation, MESH: Humans, MESH: Repetitive Sequences, Nucleic Acid, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH : Quality Control, MESH : Repetitive Sequences, Nucleic Acid, MESH : Oligonucleotide Array Sequence Analysis, MESH: Oligonucleotide Array Sequence Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Animals, MESH : Software, Software, MESH: Coloring Agents
Abstract: International audience; High-density tiling microarrays are increasingly used in combination with chromatin immunoprecipitation (ChIP) assays to delineate the regulation of gene expression. Besides the technical challenges inherent to such complex biological assays, a critical, often daunting issue is the correct interpretation of the sheer amount of raw data generated by utilizing computational methods. Here, we go through the main steps of this intricate process, including optimized chromatin immunoprecipitation on chip (ChIP-chip) data normalization, peak detection, as well as quality control reports. We also describe convenient standalone software suites, including our own, CoCAS, which works on the latest generation of Agilent high-density arrays, allows dye-swap, replicate correlation, and easy connection with genome browsers for results interpretation, or with, e.g., other peak detection algorithms. Overall, the guidelines described herein provide an effective introduction to ChIP-chip technology and analysis.
Published: 2011
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17. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101

Author: Stéphanie Herveau, Stéphane Dalle, Pablo Umana, Lina Reslan, Timothee Besseyre de Horts, Frank Herting, Thomas Friess, Charles Dumontet, Christian Klein, Adriana Plesa, Equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-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), Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hematology Laboratory, Hospices Civils de Lyon, Institut de Mathématiques de Bourgogne [Dijon] (IMB), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Mathématiques de Bourgogne [Dijon] ( IMB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre de Recherche en Cancérologie de Lyon ( CRCL )
Subjects: Cancer Research, Follicular lymphoma, MESH: Antigens, CD20, Mice, SCID, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Mice, MESH: Lymphoma, Follicular, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, MESH : Female, MESH: Animals, MESH: Mice, SCID, Cytotoxicity, Lymphoma, Follicular, MESH : Cyclophosphamide, CD20, 0303 health sciences, Antibodies, Monoclonal, 3. Good health, Oncology, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, Monoclonal, Rituximab, Female, Antibody, MESH: Dose-Response Relationship, Immunologic, medicine.drug, MESH: Xenograft Model Antitumor Assays, MESH: Cell Line, Tumor, medicine.drug_class, Dose-Response Relationship, Immunologic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH : Xenograft Model Antitumor Assays, Monoclonal antibody, Antibodies, Monoclonal, Humanized, MESH : Antibodies, Monoclonal, Humanized, 03 medical and health sciences, MESH: Gene Expression Profiling, Antigen, MESH : Antigens, CD20, Cell Line, Tumor, MESH : Mice, medicine, Animals, Humans, Cyclophosphamide, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH : Cell Line, Tumor, Gene Expression Profiling, MESH : Lymphoma, Follicular, MESH : Gene Expression Profiling, MESH : Humans, MESH: Cyclophosphamide, medicine.disease, Antigens, CD20, Xenograft Model Antitumor Assays, MESH : Mice, SCID, MESH : Antibodies, Monoclonal, Murine-Derived, MESH : Dose-Response Relationship, Immunologic, MESH: Antibodies, Monoclonal, Humanized, MESH: Antibodies, Monoclonal, Murine-Derived, biology.protein, MESH : Animals, MESH: Female
Abstract: GA101 is a novel glycoengineered Type II CD20 monoclonal antibody. When compared with rituximab, it mediates less complement-dependent cytotoxicity (CDC). As expected for a Type II antibody, GA101 appears not to act through CDC and is more potent than the Type I antibody rituximab in inducing cell death via nonclassical induction of apoptosis cytotoxicity, with more direct cytotoxicity and more antibody-dependent cell-mediated cytotoxicity. We evaluated the antitumor activity of GA101 against the human-transformed follicular lymphoma RL model in vivo in severe combined immunodeficient mice (SCID) mice. GA101 induced stronger inhibition of tumor growth than rituximab. Combination of GA101 with cyclophosphamide in vivo confirmed the superiority of GA101 over rituximab. Neutralizing the complement system with cobra venom factor partially impaired the antitumor activity of rituximab, but had no impact on the efficacy of GA101. In vitro GA101 more potently induced cell death of RL cells than rituximab. The expression of a limited number of genes was found to be induced by both antibodies after exposure in vitro. Among these, early growth response 1 and activation transcription factor 3 were confirmed to be increased at the protein level, suggesting a possible role of these proteins in the apoptotic signalling of anti-CD20 antibodies. These data imply that GA101 is superior to rituximab not only as a single agent, but also in combination with chemotherapy. These data suggest the presence of novel signalization pathways activated after exposure to anti-CD20 antibodies. Mol Cancer Ther; 10(1); 178–85. ©2011 AACR.
Published: 2011
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18. Cellular transcriptional profiling in human lung epithelial cells infected by different subtypes of influenza A viruses reveals an overall down-regulation of the host p53 pathway

Author: Catherine Nguyen, Laurence Josset, Jean-Christophe Bourdon, Bruno Lina, Jean-Jacques Diaz, Olivier Ferraris, Virginie Marcel, Olivier Terrier, Julien Textoris, Manuel Rosa-Calatrava, Gaëlle Cartet, Division of Medical Sciences, University of Dundee-Centre for Oncology and Molecular Medicine, Virologie et pathologie humaine ( VirPath ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Laboratoire de Virologie Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon ( HCL ), Technologies avancées pour le génôme et la clinique ( TAGC ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), This work was supported by University Claude Bernard of Lyon, the Civil hospitals of Lyon, the AVIESAN alliance and by a grant of the 'Programme de Recherche A (H1N1)' co-ordinated by the Institut de Microbiologie et Maladies Infectieuses (INSERM)., Virologie et pathologie humaine (VirPath), Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and BMC, Ed.
Subjects: MESH: Signal Transduction, MESH : Cell Line, MESH : Blotting, Western, medicine.disease_cause, MESH: Down-Regulation, Transcriptome, MESH : Down-Regulation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, Gene expression, Influenza A virus, MESH : Influenza, Human, MESH: Tumor Suppressor Protein p53, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH: Influenza, Human, MESH : Reverse Transcriptase Polymerase Chain Reaction, 3. Good health, MESH : Epithelial Cells, MESH : Influenza A virus, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, MESH: Epithelial Cells, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Signal Transduction, Blotting, Western, MESH: Influenza A virus, Down-Regulation, Biology, Cell Line, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, MESH: Gene Expression Profiling, Virology, Influenza, Human, medicine, Humans, MESH: Blotting, Western, lcsh:RC109-216, Gene, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, 030306 microbiology, Gene Expression Profiling, Research, MESH : Gene Expression Profiling, MESH : Humans, Epithelial Cells, Influenza A virus subtype H5N1, MESH: Cell Line, Gene expression profiling, MESH : Tumor Suppressor Protein p53, Viral replication, Cell culture, Tumor Suppressor Protein p53
Abstract: BackgroundInfluenza viruses can modulate and hijack several cellular signalling pathways to efficiently support their replication. We recently investigated and compared the cellular gene expression profiles of human lung A549 cells infected by five different subtypes of human and avian influenza viruses (Jossetet al.Plos One 2010). Using these transcriptomic data, we have focused our analysis on the modulation of the p53 pathway in response to influenza infection.ResultsOur results were supported by both RT-qPCR and western blot analyses and reveal multiple alterations of the p53 pathway during infection. A down-regulation of mRNA expression was observed for the main regulators of p53 protein stability during infection by the complete set of viruses tested, and a significant decrease in p53 mRNA expression was also observed in H5N1 infected cells. In addition, several p53 target genes were also down-regulated by these influenza viruses and the expression of their product reduced.ConclusionsOur data reveal that influenza viruses cause an overall down-regulation of the host p53 pathway and highlight this pathway and p53 protein itself as important viral targets in the altering of apoptotic processes and in cell-cycle regulation.
Published: 2011
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19. Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species

Author: Rachel Guiton, Karine Crozat, Yannick O. Alexandre, Marc Dalod, Vanessa Contreras, Michel Bonneau, Thibault Andrieu, Thien-Phong Vu Manh, Isabelle Schwartz-Cornil, Mathieu Epardaud, Ariel Savina, Nicolas Bertho, Jayne Hope, Luc Jouneau, Céline Urien, Sebastian Amigorena, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Immunologie de Marseille Luminy (CIML - INSERM U631 - CNRS UMR 6102), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Energie Atomique, Di- vision of Immuno-Virology, Direction des Sciences du Vivant, Institut des Maladies Emergentes et des The´rapies Innovantes, Fontenay-aux-Rose, Institute for Animal Health, Compton, Institut Curie, PSL Research University, INSERM U932., Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute for Animal Health (IAH), Biotechnology and Biological Sciences Research Council, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Imagerie Interventionnelle (CR2I), Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Maladies Emergentes et des Thérapies Innovantes ( IMETI ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institute for Animal Health ( IAH ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Imagerie Interventionnelle ( CR2I ), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biotechnology and Biological Sciences Research Council (BBSRC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5)
Subjects: [SDV]Life Sciences [q-bio], Conserved sequence, Immune tolerance, Interleukin 22, Mice, 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Animals, Domestic, Cells, Cultured, Conserved Sequence, Skin, 0303 health sciences, Cultured, MESH: Conserved Sequence, MESH: Dendritic Cells, MESH : Immune Tolerance, hemic and immune systems, Phenotype, Cell biology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymph, MESH: Cells, Cultured, MESH: Lymph, XCR1, MESH: Immune Tolerance, Cells, CD8 Antigens, Dipeptidyl Peptidase 4, Immunology, chemical and pharmacologic phenomena, Biology, MESH : Lymph, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Skin, Species Specificity, MESH : Conserved Sequence, MESH : Mice, MESH : Sheep, Domestic, MESH : Cells, Cultured, MESH : Skin, Immune Tolerance, MESH : Species Specificity, MESH: Species Specificity, Animals, Humans, Antigens, Gene, MESH: Mice, Sheep, Domestic, 030304 developmental biology, Sheep, MESH: Humans, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, CD8, Dendritic cell, Dendritic Cells, MESH: Dipeptidyl Peptidase 4, MESH : Dendritic Cells, MESH : Dipeptidyl Peptidase 4, MESH : Animals, MESH: Antigens, CD8, MESH: Sheep, Domestic, MESH : Antigens, CD8, MESH: Female, 030215 immunology
Abstract: International audience; The mouse lymphoid organ-resident CD8alpha(+) dendritic cell (DC) subset is specialized in Ag presentation to CD8(+) T cells. Recent evidence shows that mouse nonlymphoid tissue CD103(+) DCs and human blood DC Ag 3(+) DCs share similarities with CD8alpha(+) DCs. We address here whether the organization of DC subsets is conserved across mammals in terms of gene expression signatures, phenotypic characteristics, and functional specialization, independently of the tissue of origin. We study the DC subsets that migrate from the skin in the ovine species that, like all domestic animals, belongs to the Laurasiatheria, a distinct phylogenetic clade from the supraprimates (human/mouse). We demonstrate that the minor sheep CD26(+) skin lymph DC subset shares significant transcriptomic similarities with mouse CD8alpha(+) and human blood DC Ag 3(+) DCs. This allowed the identification of a common set of phenotypic characteristics for CD8alpha-like DCs in the three mammalian species (i.e., SIRP(lo), CADM1(hi), CLEC9A(hi), CD205(hi), XCR1(hi)). Compared to CD26(-) DCs, the sheep CD26(+) DCs show 1) potent stimulation of allogeneic naive CD8(+) T cells with high selective induction of the Ifngamma and Il22 genes; 2) dominant efficacy in activating specific CD8(+) T cells against exogenous soluble Ag; and 3) selective expression of functional pathways associated with high capacity for Ag cross-presentation. Our results unravel a unifying definition of the CD8alpha(+)-like DCs across mammalian species and identify molecular candidates that could be used for the design of vaccines applying to mammals in general.
Published: 2010
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20. Dlx homeobox gene family expression in osteoclasts

Author: Dominique Heymann, Frédéric Lézot, Alba Bolaños, Beatriz Castaneda, D. Hotton, Ariane Berdal, Bethan Thomas, Agamemnon E. Grigoriadis, G.F. Carles, Claudine Blin-Wakkach, Paul T. Sharpe, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique, physiopathologie et ingénierie du tissu osseux ( GéPITOS ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH : Cell Line, MESH : Transcription Factors, Physiology, Cellular differentiation, Clinical Biochemistry, Osteoclasts, Mandible, Mice, 0302 clinical medicine, MESH : Acid Phosphatase, Osteogenesis, MESH: Osteoclasts, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Gene Expression Regulation, Developmental, MESH : Osteogenesis, MESH: Animals, MESH : Homeodomain Proteins, MESH : Matrix Metalloproteinase 9, MESH: Osteogenesis, Tartrate-resistant acid phosphatase, Regulation of gene expression, MESH : Isoenzymes, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, DLX2, MESH : Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Developmental, Cell Differentiation, MESH: Transcription Factors, DLX6, MESH : beta-Galactosidase, DLX5, Isoenzymes, MESH: beta-Galactosidase, Matrix Metalloproteinase 9, Multigene Family, 030220 oncology & carcinogenesis, MESH: Isoenzymes, MESH : Cell Differentiation, MESH: Cell Differentiation, musculoskeletal diseases, MESH : Mandible, MESH : Male, Acid Phosphatase, MESH : Multigene Family, MESH: Mandible, Biology, Cell Line, MESH: Acid Phosphatase, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH: Homeodomain Proteins, MESH : Mice, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Homeodomain Proteins, Tartrate-Resistant Acid Phosphatase, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Matrix Metalloproteinase 9, Cell Biology, beta-Galactosidase, Molecular biology, MESH: Male, MESH: Cell Line, Gene expression profiling, MESH : Osteoclasts, MESH: Multigene Family, Homeobox, MESH : Animals, MESH : Gene Expression Regulation, Developmental, Transcription Factors
Abstract: International audience; Skeletal growth and homeostasis require the finely orchestrated secretion of mineralized tissue matrices by highly specialized cells, balanced with their degradation by osteoclasts. Time- and site-specific expression of Dlx and Msx homeobox genes in the cells secreting these matrices have been identified as important elements in the regulation of skeletal morphology. Such specific expression patterns have also been reported in osteoclasts for Msx genes. The aim of the present study was to establish the expression patterns of Dlx genes in osteoclasts and identify their function in regulating skeletal morphology. The expression patterns of all Dlx genes were examined during the whole osteoclastogenesis using different in vitro models. The results revealed that Dlx1 and Dlx2 are the only Dlx family members with a possible function in osteoclastogenesis as well as in mature osteoclasts. Dlx5 and Dlx6 were detected in the cultures but appear to be markers of monocytes and their derivatives. In vivo, Dlx2 expression in osteoclasts was examined using a Dlx2/LacZ transgenic mouse. Dlx2 is expressed in a subpopulation of osteoclasts in association with tooth, brain, nerve, and bone marrow volumetric growths. Altogether the present data suggest a role for Dlx2 in regulation of skeletal morphogenesis via functions within osteoclasts.
Published: 2010
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21. In situ protein expression in tumour spheres: development of an immunostaining protocol for confocal microscopy

Author: Bruno Saubaméa, Dominique Bellet, Virginie Dangles-Marie, Louis-Bastien Weiswald, Sophie Richon, Jean-Marc Guinebretière, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), Service de Pathologie, Hôpital René HUGUENIN (Saint-Cloud)-INSTITUT CURIE, Service de Médecine Nucléaire, INSTITUT CURIE-Hôpital René HUGUENIN (Saint-Cloud), Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique ( NAVVEC (UM 81) ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), This work was supported by Ligue Contre le Cancer, Comité Ile-de-France (Grant RS 06/75-71, RS 07/75-45), Institut National du Cancer et Cancérôpole Ile de France ('COLOMETASTEM' and 'CSC cross platform network' projects), Philippe and Denis Bloch Cancer Research Grant, Patrick Roy Translational Medicine Grant, Sally Paget-Brown Translational Research Grant, Geneviève and Jean-Paul Driot Transformative Research grant. LBW was supported by a predoctoral fellowship from the Association d'Aide à la Recherche Cancérologique de Saint-Cloud and from The Association pour la Recherche sur le Cance, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique (NAVVEC - UM 81 (UMR 8206/ U705)), Université Paris Diderot - Paris 7 (UPD7)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Hôpital René HUGUENIN (Saint-Cloud)-Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Cancer Research, MESH : Immunohistochemistry, Cell, MESH: Flow Cytometry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, 0302 clinical medicine, law, Neoplasms, Image Processing, Computer-Assisted, MESH: Microscopy, Confocal, MESH: Neoplasms, AC133 Antigen, MESH: Antigens, CD, 0303 health sciences, Microscopy, Confocal, medicine.diagnostic_test, biology, MESH: Peptides, MESH : Peptides, MESH: Gene Expression Regulation, Neoplastic, Flow Cytometry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, MESH: Image Processing, Computer-Assisted, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Technical Advance, Oncology, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, MESH : Image Processing, Computer-Assisted, MESH: Cell Line, Tumor, MESH : Flow Cytometry, MESH : Gene Expression Regulation, Neoplastic, Confocal, MESH: Glycoproteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Flow cytometry, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : Neoplastic Stem Cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, CD, Cancer stem cell, Confocal microscopy, Cell Line, Tumor, MESH : Antigens, CD, Genetics, medicine, Humans, MESH : Microscopy, Confocal, Glycoproteins, 030304 developmental biology, MESH: Humans, MESH : Cell Line, Tumor, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, CD44, MESH: Immunohistochemistry, MESH: Neoplastic Stem Cells, MESH : Neoplasms, MESH : Glycoproteins, Molecular biology, Cell culture, biology.protein, Peptides, Immunostaining
Abstract: Background Multicellular tumour sphere models have been shown to closely mimic phenotype characteristics of in vivo solid tumours, or to allow in vitro propagation of cancer stem cells (CSCs). CSCs are usually characterized by the expression of specific membrane markers using flow cytometry (FC) after enzymatic dissociation. Consequently, the spatial location of positive cells within spheres is not documented. Confocal microscopy is the best technique for the imaging of thick biological specimens after multi-labelling but suffers from poor antibody penetration. Thus, we describe here a new protocol for in situ confocal imaging of protein expression in intact spheroids. Methods Protein expression in whole spheroids (150 μm in diameter) from two human colon cancer cell lines, HT29 and CT320X6, has been investigated with confocal immunostaining, then compared with profiles obtained through paraffin immunohistochemistry (pIHC) and FC. Target antigens, relevant for colon cancer and with different expression patterns, have been studied. Results We first demonstrate that our procedure overcomes the well-known problem of antibody penetration in compact structures by performing immunostaining of EpCAM, a membrane protein expressed by all cells within our spheroids. EpCAM expression is detected in all cells, even the deepest ones. Likewise, antibody access is confirmed with CK20 and CD44 immunostaining. Confocal imaging shows that 100% of cells express β-catenin, mainly present in the plasma membrane with also cytoplasmic and nuclear staining, in agreement with FC and pIHC data. pIHC and confocal imaging show similar CA 19-9 cytoplasmic and membranar expression profile in a cell subpopulation. CA 19-9+ cell count confirms confocal imaging as a highly sensitive method (75%, 62% and 51%, for FC, confocal imaging and pIHC, respectively). Finally, confocal imaging reveals that the weak expression of CD133, a putative colon CSC marker, is restricted to the luminal cell surface of colorectal cancer acini, with CD133+ cellular debris into glandular lumina. Conclusion The present protocol enables in situ visualization of protein expression in compact three-dimensional models by whole mount confocal imaging, allowing the accurate localization and quantification of cells expressing specific markers. It should prove useful to study rare events like CSCs within tumour spheres.
Published: 2010
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22. Localizing potentially active post-transcriptional regulations in the Ewing's sarcoma gene regulatory network

Author: Ovidiu Radulescu, Bernard Delyon, Olivier Delattre, Tatiana Baumuratova, Anne Siegel, Didier Surdez, Gautier Stoll, Service de Biologie Systémique [Luxembourg], Université du Luxembourg (Uni.lu)-Faculté des Sciences, de la Technologie et de la Communication (FSTC), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, 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), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), ANR-06-BYOS-0004,SITCON,Modeling signal transduction induced by a chimeric oncogene(2006), Université du Luxembourg ( Uni.lu ) -Faculté des Sciences, de la Technologie et de la Communication (FSTC), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, 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 ), Biological systems and models, bioinformatics and sequences ( SYMBIOSE ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ), ANR-06-BYOS-0004,SITCON,Modeling signal transduction induced by a chimeric oncogene ( 2006 ), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, BMC, Ed., Biologie systémique (BIOSYS) - Modeling signal transduction induced by a chimeric oncogene - - SITCON2006 - ANR-06-BYOS-0004 - BIOSYS - VALID, and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 )
Subjects: Transcription, Genetic, MESH: Oncogenes, MESH: Insulin-Like Growth Factor I, Gene regulatory network, MESH : Insulin-Like Growth Factor I, Sarcoma ewing, MESH: Insulin-Like Growth Factor Binding Proteins, Multidisciplinaire, généralités & autres [F99] [Sciences du vivant], 0302 clinical medicine, Structural Biology, Gene Regulatory Networks, Insulin-Like Growth Factor I, MESH : Insulin-Like Growth Factor Binding Protein 3, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], lcsh:QH301-705.5, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Insulin-Like Growth Factor Binding Proteins/genetics, MESH: Gene Regulatory Networks, Genetics, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Proto-Oncogene Protein c-fli-1, Methodology Article, Applied Mathematics, MESH : Insulin-Like Growth Factor Binding Proteins, MESH: Insulin-Like Growth Factor Binding Protein 3, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH: Sarcoma, Ewing, Insulin-Like Growth Factor Binding Proteins, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, Modeling and Simulation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Software, [ INFO.INFO-IR ] Computer Science [cs]/Information Retrieval [cs.IR], MESH: Cell Line, Tumor, Systems biology, Sarcoma, Ewing, Computational biology, Multidisciplinary, general & others [F99] [Life sciences], Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Software, Qualitative analysis, Modelling and Simulation, Cell Line, Tumor, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Molecular Biology, 030304 developmental biology, MESH : Oncogenes, Oncogenes/genetics, Sarcoma, Ewing/genetics, MESH: Humans, Proto-Oncogene Protein c-fli-1, MESH : Cell Line, Tumor, Specific-information, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Transcription, Genetic, MESH : Humans, Experimental data, Ewing's sarcoma, MESH : Transcription, Genetic, Oncogenes, medicine.disease, MESH : Proto-Oncogene Protein c-fli-1, Gene expression profiling, Insulin-Like Growth Factor Binding Protein 3, MESH : Sarcoma, Ewing, lcsh:Biology (General), Proto-Oncogene Protein c-fli-1/genetics, MESH : Gene Regulatory Networks, [INFO.INFO-IR]Computer Science [cs]/Information Retrieval [cs.IR], [INFO.INFO-IR] Computer Science [cs]/Information Retrieval [cs.IR], Insulin-Like Growth Factor I/genetics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Software
Abstract: Background A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. Results We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted of post-processing the outputs of an open-source tool named BioQuali - an automatic constraint-based analysis mimicking biologist's local reasoning on a large scale. The post-processing relied on differences in the behavior of the transcriptional and post-translational levels in the network. As a case study, we analyzed a network representation of the genes and proteins controlled by an oncogene in the context of Ewing's sarcoma. The analysis allowed us to pinpoint active interactions specific to this cancer. We also identified the parts of the network which were incomplete and should be submitted for further investigation. Conclusions The proposed approach is effective for the qualitative analysis of cancer networks. It allows the integrative use of experimental data of various types in order to identify the specific information that should be considered a priority in the initial - and possibly very large - experimental dataset. Iteratively, new dataset can be introduced into the analysis to improve the network representation and make it more specific.
Published: 2010
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23. Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake

Author: Adriana Márquez-Quiñones, Dominique Langin, Karine Clément, Wim H. M. Saris, Teodora Handjieva-Darlenska, Marion Combes, Ping Wang, Andreas Pfeiffer, Dimitris K. Babalis, David M. Mutch, Thomas Meinert Larsen, Susan A. Jebb, Claus Holst, Edwin C. M. Mariman, Hubert Vidal, Arne Astrup, Nathalie Viguerie, Pavla Kalouskova, Balbine Roussel, Cyrille Debard, J. Alfredo Martínez, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Santé Publique et Informatique Médicale (SPIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Human Health and Nutritional Sciences, University of Guelph, 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), Department of Human Biology, Maastricht University [Maastricht], Institute of Preventive Medicine, Copenhagen University Hospitals, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Pharmacology and Toxicology, Medical Faculty, Medical University, Obesity Management Centre, Institute of Endocrinology, Human Nutrition Research, Elsie Widdowson Laboratory, Department of Internal Medicine, University Hospital of Heraklion, Department of Clinical Nutrition, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], European Community [FP6-513946], Institut National de la Sante et de la Recherche Medicale, Region Midi-Pyrenees, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Santé Publique et Informatique Médicale ( SPIM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Universidad de Navarra [Pamplona] ( UNAV ), Charité Universitäts Medizin Berlin, University of Copenhagen ( KU ), Centre de Recherche en Nutrition Humaine d'Ile-de-France ( CRNH-IDF ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut National Agronomique Paris-Grignon ( INA P-G ) -CETAF-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Paris 13 (UP13)-CETAF-Institut National Agronomique Paris-Grignon (INA P-G)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut de Veille Sanitaire (INVS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humane Biologie, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R1 - Metabolic Syndrome
Subjects: MESH: Treatment Failure, Blood Pressure, MESH: Energy Intake, Transcriptome, 0302 clinical medicine, HIGH-PROTEIN, Models, MESH: Models, Genetic, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, MESH: Treatment Outcome, 0303 health sciences, MACRONUTRIENT, Reducing, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Blood Pressure, MESH: Follow-Up Studies, LOW-FAT, Gene expression profiling, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, LOSS MAINTENANCE, MESH : Adipose Tissue, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Weight Loss, MESH : Treatment Failure, Genetic, Humans, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, Anthropometry, medicine.disease, Obesity, Endocrinology, MICROARRAY DATA, Energy intake, MESH: Female, Calorie, Time Factors, Medicine (miscellaneous), Adipose tissue, MESH : Models, Genetic, HUMAN OBESITY, Weight loss, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : RNA, MESH: Obesity, MESH : Female, Treatment Failure, MESH : Diet, Reducing, 2. Zero hunger, MESH: Diet, Reducing, Nutrition and Dietetics, Reverse Transcriptase Polymerase Chain Reaction, MESH : Adult, ADIPOCYTES, Glycemic index, Treatment Outcome, MESH : Obesity, Female, medicine.symptom, Dieting, MESH : Time Factors, Adult, 030209 endocrinology & metabolism, MESH : Treatment Outcome, Biology, DiOGenes, MESH: RNA, Internal medicine, Weight Loss, medicine, MESH : Blood Pressure, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, LOSS DIETS, Models, Genetic, Gene Expression Profiling, MESH: Time Factors, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, GLYCEMIC INDEX, RNA, MESH : Weight Loss, Energy Intake, Follow-Up Studies
Abstract: Background: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. Objective: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. Design: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. Conclusions: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control. This trial was registered at clinicaltrials.gov as NCT00390637. © 2010 American Society for Nutrition.
Published: 2010
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24. Identification of small RNAs in Francisella tularensis

Author: Guillaume Postic, Eric Frapy, Marion Dupuis, Alain Charbit, Jonathan Livny, Iharilalao Dubail, Karin L. Meibom, Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston] ( MGH ) -Massachusetts Institute of Technology ( MIT ), Channing Laboratories, Brigham and Women's Hospital [Boston], Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], and BMC, Ed.
Subjects: MESH : Molecular Sequence Data, MESH : DNA, Complementary, MESH : Nucleic Acid Conformation, Intracellular Space, MESH : Intracellular Space, MESH: Base Sequence, Genome, RNA Transport, Mice, MESH: RNA Transport, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, Cloning, Molecular, Francisella tularensis, MESH : RNA Transport, Oligonucleotide Array Sequence Analysis, MESH : Macrophages, Genetics, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, MESH : Francisella tularensis, Reverse Transcriptase Polymerase Chain Reaction, MESH : Blotting, Northern, MESH : Reverse Transcriptase Polymerase Chain Reaction, Bacterial vaccine, MESH: Reproducibility of Results, RNA, Bacterial, MESH : Oligonucleotide Array Sequence Analysis, MESH: Nucleic Acid Conformation, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Bacterial Vaccines, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Intracellular Space, DNA microarray, MESH : Mutation, MESH: RNA, Bacterial, Biotechnology, Research Article, MESH: Computational Biology, MESH : Gene Expression Regulation, Bacterial, DNA, Complementary, MESH: Mutation, lcsh:QH426-470, MESH : Cloning, Molecular, lcsh:Biotechnology, In silico, Molecular Sequence Data, Context (language use), Biology, Vaccines, Attenuated, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Francisella tularensis, lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Vaccines, Attenuated, MESH : Mice, Animals, MESH: Blotting, Northern, MESH: Cloning, Molecular, MESH : Vaccines, Attenuated, MESH: Mice, 030304 developmental biology, MESH: Molecular Sequence Data, Base Sequence, 030306 microbiology, Gene Expression Profiling, Macrophages, MESH : Reproducibility of Results, MESH : Gene Expression Profiling, RNA, Computational Biology, Reproducibility of Results, MESH: Macrophages, Gene Expression Regulation, Bacterial, MESH: DNA, Complementary, MESH : RNA, Bacterial, biology.organism_classification, Blotting, Northern, Gene expression profiling, MESH : Bacterial Vaccines, lcsh:Genetics, Mutation, MESH: Oligonucleotide Array Sequence Analysis, Nucleic Acid Conformation, MESH : Base Sequence, MESH : Animals, MESH: Bacterial Vaccines, MESH : Computational Biology
Abstract: Background Regulation of bacterial gene expression by small RNAs (sRNAs) have proved to be important for many biological processes. Francisella tularensis is a highly pathogenic Gram-negative bacterium that causes the disease tularaemia in humans and animals. Relatively little is known about the regulatory networks existing in this organism that allows it to survive in a wide array of environments and no sRNA regulators have been identified so far. Results We have used a combination of experimental assays and in silico prediction to identify sRNAs in F. tularensis strain LVS. Using a cDNA cloning and sequencing approach we have shown that F. tularensis expresses homologues of several sRNAs that are well-conserved among diverse bacteria. We have also discovered two abundant putative sRNAs that share no sequence similarity or conserved genomic context with any previously annotated regulatory transcripts. Deletion of either of these two loci led to significant changes in the expression of several mRNAs that likely include the cognate target(s) of these sRNAs. Deletion of these sRNAs did not, however, significantly alter F. tularensis growth under various stress conditions in vitro, its replication in murine cells, or its ability to induce disease in a mouse model of F. tularensis infection. We also conducted a genome-wide in silico search for intergenic loci that suggests F. tularensis encodes several other sRNAs in addition to the sRNAs found in our experimental screen. Conclusion Our findings suggest that F. tularensis encodes a significant number of non-coding regulatory RNAs, including members of well conserved families of structural and housekeeping RNAs and other poorly conserved transcripts that may have evolved more recently to help F. tularensis deal with the unique and diverse set of environments with which it must contend.
Published: 2010
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25. Expression profiling of prospero in the Drosophila larval chemosensory organ: Between growth and outgrowth

Author: Laure Guenin, Mahatsangy Raharijaona, Rémi Houlgatte, Fawzia Baba-Aissa, Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris], Développement et Communication Chimique chez les Insectes (DCCI), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was funded by the Burgundy Regional Council and the Centre National de la Recherche Scientifique., Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ), BMC, Ed., Institut Pasteur [Paris] (IP), and Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Central Nervous System, MESH : Transcription Factors, MESH: Drosophila, OF-FUNCTION SCREEN, MUSCA-DOMESTICA L, HOUSE-FLY LARVA, FINE-STRUCTURE, AXON GUIDANCE, TRANSCRIPTION FACTOR, PATTERN-FORMATION, GENETIC-ANALYSIS, NERVOUS-SYSTEM, Genes, Insect, MESH: Genes, Insect, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Cluster Analysis, Drosophila Proteins, MESH: Animals, MESH: Nerve Tissue Proteins, MESH : Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, MESH : Central Nervous System, Microbiology and Parasitology, MESH : Genes, Insect, Gene Expression Regulation, Developmental, Nuclear Proteins, MESH: Transcription Factors, Null allele, Microbiologie et Parasitologie, MESH : Oligonucleotide Array Sequence Analysis, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Larva, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Drosophila, Drosophila Protein, Research Article, Biotechnology, lcsh:QH426-470, MESH: Drosophila Proteins, lcsh:Biotechnology, Nerve Tissue Proteins, Biotechnologies, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:TP248.13-248.65, Animals, MESH : Cluster Analysis, MESH: Central Nervous System, Allele, MESH : Drosophila, Alleles, 030304 developmental biology, MESH : Larva, Microarray analysis techniques, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Alleles, Wild type, MESH : Nuclear Proteins, Prospero, biology.organism_classification, MESH : Drosophila Proteins, MESH: Cluster Analysis, Gene expression profiling, lcsh:Genetics, MESH: Oligonucleotide Array Sequence Analysis, Homeobox, MESH : Animals, MESH : Gene Expression Regulation, Developmental, MESH : Alleles, MESH: Nuclear Proteins, MESH: Larva, 030217 neurology & neurosurgery, Transcription Factors
Abstract: BackgroundThe antenno-maxilary complex (AMC) forms the chemosensory system of theDrosophilalarva and is involved in gustatory and olfactory perception. We have previously shown that a mutant allele of the homeodomain transcription factor Prospero (prosVoila1,V1), presents several developmental defects including abnormal growth and altered taste responses. In addition, many neural tracts connecting the AMC to the central nervous system (CNS) were affected. Our earlier reports on larval AMC did not argue in favour of a role ofprosin cell fate decision, but strongly suggested thatproscould be involved in the control of other aspect of neuronal development. In order to identify these functions, we used microarray analysis of larval AMC and CNS tissue isolated from the wild type, and three other previously characterisedprosperoalleles, including theV1mutant, considered as a null allele for the AMC.ResultsA total of 17 samples were first analysed with hierarchical clustering. To determine those genes affected by loss ofprosfunction, we calculated a discriminating score reflecting the differential expression betweenV1mutant and otherprosalleles. We identified a total of 64 genes in the AMC. Additional manual annotation using all the computed information on the attributed role of these genes in theDrosophilalarvae nervous system, enabled us to identify one functional category of potential Prospero target genes known to be involved in neurite outgrowth, synaptic transmission and more specifically in neuronal connectivity remodelling. The second category of genes found to be differentially expressed between the null mutant AMC and the other alleles concerned the development of the sensory organs and more particularly the larval olfactory system. Surprisingly, a third category emerged from our analyses and suggests an association ofproswith the genes that regulate autophagy, growth and insulin pathways. Interestingly, EGFR and Notch pathways were represented in all of these three functional categories. We now propose that Pros could perform all of these different functions through the modulation of these two antagonistic and synergic pathways.ConclusionsThe current data contribute to the clarification of theprosperofunction in the larval AMC and show thatprosregulates different function in larvae as compared to those controlled by this gene in embryos. In the future, the possible mechanism by which Pros could achieve its function in the AMC will be explored in detail.
Published: 2010
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26. Analysis of gene transcription in sera during chronic hepatitis C infection

Author: Matthieu Carrière, Hervé Groux, Nadira Delhem, Olivier Moralès, Véronique Pancré, Philippe Podevin, Céline Miroux, Arnaud Carpentier, Filomena Conti, Yvon Calmus, Claude Auriault, Lynda Aoudjehane, Institut de Biologie de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire, UPRES 1833, Service de Chirurgie Digestive, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunosearch, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato Gastroentérologie, Centre Hospitalier Léon Binet, Virologie de l'hépatite C (EA 4474), Université Paris Descartes - Paris 5 (UPD5), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Cochin [AP-HP], Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Virologie de l'hépatite C ( EA 4474 ), Université Paris Descartes - Paris 5 ( UPD5 ), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : RNA, Messenger, Hepacivirus, Statistics as Topic, MESH : Statistics as Topic, MESH : Leukocytes, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, medicine.disease_cause, MESH : Hepacivirus, Pathogenesis, Liver disease, 0302 clinical medicine, Gene expression, Leukocytes, MESH : Serum, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Hepacivirus, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, MESH : Host-Pathogen Interactions, 0303 health sciences, MESH: Middle Aged, biology, MESH: Serum, Hepatitis C, Middle Aged, MESH : Adult, 3. Good health, MESH: Hepatitis C, Chronic, Infectious Diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Host-Pathogen Interactions, HCV, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Adult, medicine.medical_specialty, MESH : Hepatitis C, Chronic, Hepatitis C virus, MESH : Male, mRNA, liver, MESH: Leukocytes, 03 medical and health sciences, MESH: Gene Expression Profiling, Virology, Molecular genetics, medicine, Humans, MESH : Middle Aged, RNA, Messenger, MESH: Statistics as Topic, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH: Host-Pathogen Interactions, MESH : Liver, MESH: Adult, Hepatitis C, Chronic, medicine.disease, biology.organism_classification, Molecular biology, MESH: Male, Gene expression profiling, Immunology, PBMCs, transcriptome, serum, MESH: Female, MESH: Liver
Abstract: International audience; Alternative, non-invasive techniques are necessary to monitor the progression of liver disease during chronic hepatitis C. Firstly, because serum is the most accessible material for studies using qPCR in microplates, gene transcription was compared in 219 selected genes involved in the pathogenesis of hepatitis C virus (HCV) infection between sera, PBMCs and liver samples collected simultaneously from five patients infected chronically. Secondly, using sera, gene profiles were compared between HCV-infected patients (n = 10) and healthy controls (n = 10). In addition, the influence of alcohol intake was examined in patients infected with HCV genotype-1. Firstly, amplifiable mRNAs were obtained in all samples. After amplification, significant correlations were observed between: liver versus serum; liver versus PBMCs; and serum versus PBMCs (r(2) = 0.37, r(2) = 0.54, r(2) = 0.49, respectively). A comparison of gene transcription by gene involved in T- and B-cell markers, adhesion molecules, apoptosis, liver matrix turnover and inflammation, revealed comparable, significant correlations between serum and liver, (r(2) = 0.30, r(2) = 0.60, r(2) = 0.51, r(2) = 0.51, r(2) = 0.26, and r(2) = 0.61 respectively). Secondly, a quantitative analysis of gene expression in sera between genotype-1b-infected patients and healthy controls revealed that 41 genes involved closely in T-cell activation and apoptosis were over-expressed significantly in patients infected with HCV. In these patients, alcohol consumption was associated with an increased expression of six genes involved in the inflammatory response, together with a decrease of genes associated with dendritic cell function. It is concluded that in patients infected with HCV, serum can be used to evaluate expression of liver genes. Further prospective studies are clearly needed to validate the initial results and to define the relevant genes.
Published: 2009
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27. Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549

Author: Stéphane Bretagne, Anne-Pauline Bellanger, Ingrid Laurendeau, Laurence Millon, Ivan Bièche, Françoise Botterel, D Rivollet, Michel Vidaud, Khaled Khoufache, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Genetique Moleculaire des Cancers d'Origine Epitheliale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Service de parasitologie [Mondor], Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE
Subjects: MESH : Cell Line, MESH : Spores, Fungal, Necrosis, MESH : Respiratory Mucosa, MESH : Cytokines, Penicillium chrysogenum, Polymerase Chain Reaction, Aspergillus fumigatus, MESH: Respiratory Mucosa, MESH : Immunosuppressive Agents, skin and connective tissue diseases, MESH : Polymerase Chain Reaction, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, MESH: Cytokines, biology, Interleukin, General Medicine, Spores, Fungal, MESH : Epithelial Cells, MESH: Epithelial Cells, Cytokines, Steroids, Tumor necrosis factor alpha, MESH: Immunosuppressive Agents, medicine.symptom, MESH: Aspergillus fumigatus, MESH: Penicillium chrysogenum, Immunosuppressive Agents, Microbiology (medical), MESH : Penicillium chrysogenum, Inflammation, Respiratory Mucosa, Microbiology, Cell Line, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Spores, Fungal, medicine, Humans, Interleukin 8, 030304 developmental biology, A549 cell, MESH: Humans, 030306 microbiology, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, Epithelial Cells, MESH: Polymerase Chain Reaction, biology.organism_classification, MESH: Steroids, MESH: Cell Line, MESH : Aspergillus fumigatus, Respiratory epithelium, MESH : Steroids
Abstract: Inhalation of conidia is the main cause of invasive pulmonary aspergillosis (IPA) and the respiratory epithelium is the first line of defence. To explore the triggering factor for the inflammatory response toAspergillus fumigatus, the species mainly responsible for IPA, this study analysed the differential expression of three inflammatory genes in A549 cells after challenge with live and killed conidia. The influence of steroids, one of the main risk factors for developing IPA, was also investigated. Quantification of mRNAs of the inflammatory mediator genes encoding interleukin (IL)-8, tumour necrosis factor (TNF)-αand granulocyte–monocyte colony-stimulating factor (GM-CSF) was carried out using real-time PCR. Ingestion rates were studied for the conidia ofA. fumigatusandPenicillium chrysogenumusing a fluorescence brightener. Similar results were obtained for both species, with ingestion rates ranging from 35 to 40 %. Exposure of A549 cells to liveA. fumigatusconidia only induced a four- to fivefold increase in the mRNA levels of the three genes, starting 8 h after the initial contact. Both inactivation of liveA. fumigatusconidia and treatment by dexamethasone (10−7 M) prevented the overexpression of TNF-α, IL-8 and GM-CSF. Fungal growth, rather than conidia ingestion, appears to be the main stimulus for the production of inflammatory mediators by epithelial cells, and this production is inhibited by steroid therapy. These results underline the role that the epithelium plays in the innate response against IPA.
Published: 2009
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28. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours

Author: Camilla Pilati, Tina Izard, Charles Balabaud, Sandrine Imbeaud, Gabrielle Couchy, Paulette Bioulac-Sage, Karine Poussin, Jessica Zucman-Rossi, Mohamed Amessou, Sandra Rebouissou, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex Immuno-oncology, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Genexpress, Génomique Fonctionnelle et Biologie Systémique pour la Santé, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Department of Cancer Biology, The Scripps Research Institute [La Jolla, San Diego], Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, ARC, LNCC, Inca, fondation de france, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), The Scripps Research Institute, Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Zucman-Rossi, Jessica
Subjects: MESH: Inflammation, MESH: Signal Transduction, Somatic cell, MESH : heaptocellular carcinoma, MESH: mutation, MESH: Adenoma, Liver Cell, 0302 clinical medicine, oncogene, MESH : STAT3 Transcription Factor, Cytokine Receptor gp130, MESH : Interferons, MESH: Interferons, STAT3, Sequence Deletion, Regulation of gene expression, 0303 health sciences, Multidisciplinary, biology, MESH: STAT3 Transcription Factor, MESH: Gene Expression Regulation, Neoplastic, MESH: Sequence Deletion, Gene Expression Regulation, Neoplastic, MESH : mutation, MESH : Cytokine Receptor gp130, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.symptom, Signal Transduction, STAT3 Transcription Factor, MESH: Cell Line, Tumor, MESH : Interleukin-6, Adenoma, MESH : Gene Expression Regulation, Neoplastic, hepatocellular adenoma, MESH : gp130, heaptocellular carcinoma, Inflammation, MESH : oncogene, Article, Adenoma, Liver Cell, 03 medical and health sciences, gp130, MESH: Gene Expression Profiling, MESH : Adenoma, Liver Cell, Cell Line, Tumor, medicine, Humans, MESH: gp130, MESH : hepatocellular adenoma, 030304 developmental biology, MESH : Signal Transduction, MESH : Inflammation, MESH: Humans, Interleukin-6, MESH : Cell Line, Tumor, Gene Expression Profiling, MESH : Sequence Deletion, MESH : Gene Expression Profiling, MESH : Humans, MESH: hepatocellular adenoma, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular adenoma, medicine.disease, MESH: heaptocellular carcinoma, MESH: Interleukin-6, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, MESH: Cytokine Receptor gp130, inflammation, biology.protein, Cancer research, Inflammatory Hepatocellular Adenoma, Interferons, mutation, MESH: oncogene
Abstract: International audience; Inflammatory hepatocellular adenomas are benign liver tumours defined by the presence of inflammatory infiltrates and by the increased expression of inflammatory proteins in tumour hepatocytes. Here we show a marked activation of the interleukin (IL)-6 signalling pathway in this tumour type; sequencing candidate genes pinpointed this response to somatic gain-of-function mutations in the IL6ST gene, which encodes the signalling co-receptor gp130. Indeed, 60% of inflammatory hepatocellular adenomas harbour small in-frame deletions that target the binding site of gp130 for IL-6, and expression of four different gp130 mutants in hepatocellular cells activates signal transducer and activator of transcription 3 (STAT3) in the absence of ligand. Furthermore, analysis of hepatocellular carcinomas revealed that rare gp130 alterations are always accompanied by beta-catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain-of-function gp130 mutations in these human hepatocellular adenomas fully explains activation of the acute inflammatory phase observed in tumourous hepatocytes, and suggests that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation.
Published: 2009
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29. Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays

Author: Elodie Manié, Emmanuel Barillot, Marc-Henri Stern, Tatiana Popova, Dominique Stoppa-Lyonnet, Guillem Rigaill, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Biologie des Tumeurs, INSTITUT CURIE, Mathématiques et Informatique Appliquées ( MIA-Paris ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Département de recherche translationnelle, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, This work is part of the 'Cancéropôle Ile-de-France-Région Ile-de-France-Hereditary Breast Cancer' program coordinated by DSL and MHS. This work also was supported by the INSERM, the Institut Curie, and its Translational Research Department. TP is supported by a grant from the Cancéropôle Ile-de-France-Région Ile-de-France. GR is supported by a grant from the Institut National du Cancer (INCa)., Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie, Mathématiques et Informatique Appliquées (MIA-Paris), AgroParisTech-Institut National de la Recherche Agronomique (INRA), MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Département de Recherche Translationnelle, Mines Paris - PSL (École nationale supérieure des mines de Paris), and BMC, Ed.
Subjects: Method, Loss of Heterozygosity, MESH : Models, Genetic, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, Allelic Imbalance, MESH : Breast Neoplasms, Genome, Loss of heterozygosity, MESH: Genotype, Automation, MESH: Ploidies, 0302 clinical medicine, Models, MESH: Automation, Genotype, MESH: Models, Genetic, MESH : Karyotyping, Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genomics, Homozygote, MESH : Polymorphism, Single Nucleotide, Single Nucleotide, Genomics, MESH: Gene Expression Regulation, Neoplastic, SDV:GEN, Gene Expression Regulation, Neoplastic, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, MESH : Ploidies, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Homozygote, MESH : Gene Expression Regulation, Neoplastic, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Homozygote, Genetic, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], SNP, Humans, MESH: Genome, Polymorphism, MESH : Allelic Imbalance, 030304 developmental biology, MESH: Loss of Heterozygosity, Neoplastic, [SDV.GEN]Life Sciences [q-bio]/Genetics, Ploidies, MESH: Humans, Models, Genetic, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Genomics, MESH : Humans, MESH: Allelic Imbalance, Gene Expression Regulation, Karyotyping, SDV:BBM:GTP, Human genetics, MESH : Automation, Gene expression profiling, MESH: Karyotyping, MESH : Genome, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Breast Neoplasms, MESH : Loss of Heterozygosity
Abstract: GAP, a method for analyzing complex cancer genome profiles from SNP arrays, performs well even with poor quality data and rearranged genomes, We describe a method for automatic detection of absolute segmental copy numbers and genotype status in complex cancer genome profiles measured with single-nucleotide polymorphism (SNP) arrays. The method is based on pattern recognition of segmented and smoothed copy number and allelic imbalance profiles. Assignments were verified by DNA indexes of primary tumors and karyotypes of cell lines. The method performs well even for poor-quality data, low tumor content, and highly rearranged tumor genomes.
Published: 2009
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30. The CDK4-pRB-E2F1 pathway controls insulin secretion

Author: Stéphane Dalle, Lluis Fajas, Safia Costes, Emilie Blanchet, Said Assou, Jean-Sébastien Annicotte, Irena Iankova, Claude Sardet, Carine Chavey, Jacques Teyssier, INSERM, U834, Montpellier, F-34298, France, Métabolisme et cancer, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Institut de recherche en biothérapie ( IRB ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Université de Montpellier ( UM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Arnaud de Villeuneuve Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), INSERM-Association Française des Diabétiques (PNR-Diabète), Association pour la Recherche contre le Cancer, and Fondation pour la Recherche Médicale. E.B. is supported by a grant form the Ministère de l'Enseignement Supérieur et de la Recherche, C.C. is supported by a grant from the Agence Nationale pour la Recherche., Agence Nationale pour la Recherche (ANR physio2006),Agence Nationale pour la Recherche (ANR physio2006), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Agence Nationale pour la Recherche (ANR physio2006), Le Ster, Yves, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_treatment, MESH : Blotting, Western, MESH : RNA, Small Interfering, MESH : E2F1 Transcription Factor, MESH : Phosphorylation, Mice, 0302 clinical medicine, Insulin Secretion, Glucose homeostasis, Insulin, MESH: Animals, ComputingMilieux_MISCELLANEOUS, MESH: Chromatin Immunoprecipitation, 0303 health sciences, Retinoblastoma protein, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Protein Binding, Transfection, [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, Immunohistochemistry, Cell biology, MESH: COS Cells, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, COS Cells, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], endocrine system, Blotting, Western, MESH: Insulin, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, Islets of Langerhans, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Blotting, Western, MESH: Protein Binding, MESH : Islets of Langerhans, Potassium Channels, Inwardly Rectifying, neoplasms, MESH: Phosphorylation, MESH : Glucose, MESH: Islets of Langerhans, MESH : Gene Expression Profiling, MESH: Cercopithecus aethiops, MESH: Cell Line, Mice, Inbred C57BL, Insulin receptor, Glucose, MESH : Cercopithecus aethiops, Chromatin immunoprecipitation, MESH: Signal Transduction, MESH : Cell Line, MESH : Immunohistochemistry, MESH : Insulin, [SDV]Life Sciences [q-bio], MESH : Models, Biological, MESH: Mice, Knockout, Retinoblastoma Protein, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: RNA, Small Interfering, Chlorocebus aethiops, Phosphorylation, RNA, Small Interfering, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mice, Knockout, biology, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Reverse Transcriptase Polymerase Chain Reaction, MESH: Potassium Channels, Inwardly Rectifying, MESH: E2F1 Transcription Factor, MESH: Glucose, MESH : Cyclin-Dependent Kinase 4, Regulatory Pathway, Signal transduction, MESH : Transfection, biological phenomena, cell phenomena, and immunity, MESH : COS Cells, Protein Binding, Signal Transduction, Chromatin Immunoprecipitation, MESH: Cyclin-Dependent Kinase 4, MESH : Mice, Inbred C57BL, Models, Biological, Cell Line, MESH : Chromatin Immunoprecipitation, MESH: Mice, Inbred C57BL, MESH : Mice, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH: Mice, 030304 developmental biology, MESH : Signal Transduction, MESH: Transfection, Gene Expression Profiling, MESH: Models, Biological, Cyclin-Dependent Kinase 4, MESH: Immunohistochemistry, Cell Biology, MESH: Retinoblastoma Protein, MESH : Potassium Channels, Inwardly Rectifying, biology.protein, MESH : Mice, Knockout, MESH : Animals, MESH : Retinoblastoma Protein, E2F1 Transcription Factor
Abstract: International audience; CDK4-pRB-E2F1 cell-cycle regulators are robustly expressed in non-proliferating beta cells, suggesting that besides the control of beta-cell number the CDK4-pRB-E2F1 pathway has a role in beta-cell function. We show here that E2F1 directly regulates expression of Kir6.2, which is a key component of the K(ATP) channel involved in the regulation of glucose-induced insulin secretion. We demonstrate, through chromatin immunoprecipitation analysis from tissues, that Kir6.2 expression is regulated at the promoter level by the CDK4-pRB-E2F1 pathway. Consistently, inhibition of CDK4, or genetic inactivation of E2F1, results in decreased expression of Kir6.2, impaired insulin secretion and glucose intolerance in mice. Furthermore we show that rescue of Kir6.2 expression restores insulin secretion in E2f1(-/-) beta cells. Finally, we demonstrate that CDK4 is activated by glucose through the insulin pathway, ultimately resulting in E2F1 activation and, consequently, increased expression of Kir6.2. In summary we provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose homeostasis, defining a new link between cell proliferation and metabolism.
Published: 2008
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31. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab

Author: Pierre Feugier, Eric Labouyrie, Hervé Tilly, Felix Reyes, A. de Reyniès, David S. Rickman, Françoise Berger, Corinne Haioun, Gilles Salles, Karen Leroy, Christian Gisselbrecht, Thierry Jo Molina, Christian Bastard, Bertrand Coiffier, J-P Jais, Josette Brière, P. Gaulard, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ), Programme CIT, Ligue Nationale Contre le Cancer, Service d'Anatomo-Pathologie, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'anatomo-pathologie [Paris], Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Département de pathologie [Mondor], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Anatomie et Cytologie Pathologiques, Service d'Hématologie, CRLCC Henri Becquerel, Service de génétique oncologique, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Guellaen, Georges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), Ligue Nationale Contre le Cancer (LNCC), Hospices Civils de Lyon (HCL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Oncology, Male, Cellular immunity, MESH: Cytoskeletal Proteins, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH: Metalloproteins, MESH : Aged, MESH: Antibodies, Monoclonal, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, 80 and over, MESH : Cytidine Deaminase, Aged, 80 and over, 0303 health sciences, Hematology, MESH: Middle Aged, MESH : Reverse Transcriptase Polymerase Chain Reaction, Antibodies, Monoclonal, LIM Domain Proteins, Diffuse, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Vincristine, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Rituximab, MESH : DNA-Binding Proteins, MESH : Vincristine, medicine.medical_specialty, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Doxorubicin, MESH: Forkhead Transcription Factors, Large B-Cell, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Cyclophosphamide, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH: Cyclophosphamide, MESH : Prednisone, MESH : Cytoskeletal Proteins, medicine.disease, Lymphoma, Cytoskeletal Proteins, rab GTP-Binding Proteins, Immunology, Diffuse large B-cell lymphoma, MESH: Female, MESH: Prednisone, Cancer Research, MESH : rab GTP-Binding Proteins, APOBEC-3G Deaminase, CHOP, MESH : Lymphoma, Large B-Cell, Diffuse, Antibodies, Monoclonal, Murine-Derived, International Prognostic Index, MESH: Aged, 80 and over, MESH : Metalloproteins, immune system diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, Monoclonal, MESH : Female, MESH : Cyclophosphamide, MESH: Aged, Reverse Transcriptase Polymerase Chain Reaction, Forkhead Transcription Factors, Middle Aged, DNA-Binding Proteins, MESH : Forkhead Transcription Factors, MESH : Antibodies, Monoclonal, Female, Lymphoma, Large B-Cell, Diffuse, MESH : Repressor Proteins, medicine.drug, MESH : Male, MESH: Vincristine, Biology, Antibodies, MESH: Multivariate Analysis, Proto-Oncogene Proteins, Internal medicine, Cytidine Deaminase, Metalloproteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Doxorubicin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Cytidine Deaminase, Gene Expression Profiling, MESH : Multivariate Analysis, MESH: Male, Repressor Proteins, MESH: rab GTP-Binding Proteins, Doxorubicin, Multivariate Analysis, Prednisone, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: DNA-Binding Proteins
Abstract: International audience; Gene expression profiles have been associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)-CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used this data set to select transcripts showing an association with progression-free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative reverse transcription-PCR in the 23 R-CHOP samples of the screening set and an additional 44 R-CHOP samples set to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell-of-origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising four genes of the cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy.
Published: 2008
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32. FOXO1 regulates L-Selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase

Author: Christine Denoyelle, Nicolas Cagnard, Vladimir Lazar, Anne Dubart-Kupperschmitt, Georges Bismuth, Stéphanie Fabre, Florent Carrette, David A. Fruman, Marianne Mangeney, Valérie Lang, Jing Chen, Monique Semichon, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Department of Molecular Biology and Biochemistry, and Center for Immunology, University of California [Irvine] (UCI), Proteomic unit, Centro de Investigacion Cooperativa en Biociencias, Département de la Recherche Clinique et du Développement, Assistance publique - Hôpitaux de Paris (AP-HP), Unité de génomique fonctionnelle, Institut Gustave Roussy (IGR), Garcia, Marie, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and University of California-University of California
Subjects: MESH : Protein Biosynthesis, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, T-Lymphocytes, MESH: Chemotaxis, Leukocyte, MESH : Kruppel-Like Transcription Factors, Phosphatidylinositol 3-Kinases, MESH : 1-Phosphatidylinositol 3-Kinase, Transcriptional regulation, Immunology and Allergy, MESH: L-Selectin, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, L-Selectin, Cells, Cultured, Regulation of gene expression, MESH : Gene Expression Regulation, Forkhead Box Protein O1, MESH : Chemotaxis, Leukocyte, Forkhead Transcription Factors, MESH: Receptors, Lysosphingolipid, MESH: Gene Expression Regulation, Cell biology, MESH : Forkhead Transcription Factors, Chemotaxis, Leukocyte, Receptors, Lysosphingolipid, medicine.anatomical_structure, MESH: Protein Biosynthesis, L-selectin, MESH: Kruppel-Like Transcription Factors, MESH : L-Selectin, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured, endocrine system, T cell, proliferation, Immunology, Kruppel-Like Transcription Factors, Biology, foxo, MESH: Gene Expression Profiling, Cell quiescence, MESH: Forkhead Transcription Factors, MESH : Cells, Cultured, medicine, Humans, Transcription factor, PI3K/AKT/mTOR pathway, MESH : Receptors, Lysosphingolipid, MESH : T-Lymphocytes, MESH: Humans, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, MESH: 1-Phosphatidylinositol 3-Kinase, DNA, human T lymphocytes, Molecular biology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, MESH: T-Lymphocytes, [INFO.INFO-BT] Computer Science [cs]/Biotechnology, Gene Expression Regulation, Protein Biosynthesis, biology.protein, Homing (hematopoietic)
Abstract: In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1 also increases transcripts of EDG1 and EDG6, two sphingosine-1-phosphate receptors that regulate lymphocyte trafficking. Additionally, FOXO1 binds the promoter of the cell quiescence and homing regulator Krüppel-like factor 2 and regulates its expression. Together, these results reveal a new function of FOXO1 in the immune system and suggest that PI3K controls a coordinated network of transcription factors regulating both cell quiescence and homing of human T lymphocytes.
Published: 2008

33. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver

Author: Léon Kautz, Annabelle Monnier, Delphine Meynard, Marie-Paule Roth, Régis Bouvet, Valérie Darnaud, Chiuxia Deng, Hélène Coppin, Jean Mosser, Sophie Vaulont, Rui-Hong Wang, 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), Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Moléculaire et Génomique, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR, programme IRONGENES, Commission européenne (LSHM-CT-2006-037296 : EUROIRON1), Association pour la Recherche sur le Cancer (ARC), ANR-05-MRAR-0031,IRONGENES,Intégration d'approches génétiques et génomiques pour l'identification des gènes modificateurs impliqués dans l'hémochromatose génétique(2005), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), ANR: IRONGENES,IRONGENES, Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-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)-Université de Rennes 1 (UR1), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ecosystèmes, biodiversité, évolution [Rennes] ( ECOBIO ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -INEE-Observatoire des Sciences de l'Univers de Rennes ( OSUR ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), ANR : IRONGENES,IRONGENES, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique moléculaire et Génomique [CHU Rennes], and CHU Pontchaillou [Rennes]
Subjects: Male, MESH: Signal Transduction, Transcription, Genetic, MESH : Basic Helix-Loop-Helix Transcription Factors, Bone Morphogenetic Protein 6, MESH: Bone Morphogenetic Protein 6, MESH: Bone Morphogenetic Proteins, Smad Proteins, SMAD, Biochemistry, MESH: Mice, Knockout, MESH : Iron, Mice, MESH : Phosphorylation, MESH : Smad1 Protein, MESH : Bone Morphogenetic Proteins, 0302 clinical medicine, Transcription (biology), Gene expression, MESH: Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, MESH: Smad4 Protein, MESH: Animals, Phosphorylation, Smad4 Protein, Mice, Knockout, 2. Zero hunger, 0303 health sciences, MESH: Iron, biology, MESH : Smad5 Protein, Hematology, Erythroferrone, Cell biology, Liver, 030220 oncology & carcinogenesis, Bone Morphogenetic Proteins, MESH: Smad7 Protein, Signal transduction, MESH : Smad7 Protein, Signal Transduction, Smad5 Protein, Iron Overload, Iron, MESH : Male, Immunology, Active Transport, Cell Nucleus, MESH: Active Transport, Cell Nucleus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Smad1 Protein, Smad7 Protein, MESH : Diet, 03 medical and health sciences, MESH: Smad5 Protein, MESH: Gene Expression Profiling, MESH: Iron Overload, MESH: Diet, Hepcidin, MESH : Mice, Animals, MESH : Smad Proteins, MESH: Mice, MESH : Active Transport, Cell Nucleus, 030304 developmental biology, Hemojuvelin, MESH : Signal Transduction, MESH : Iron Overload, MESH: Phosphorylation, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Transcription, Genetic, MESH: Smad1 Protein, MESH : Transcription, Genetic, MESH : Liver, MESH : Smad4 Protein, MESH: Smad Proteins, Cell Biology, MESH: Male, Diet, Smad8 Protein, biology.protein, MESH : Mice, Knockout, MESH: Smad8 Protein, MESH : Animals, MESH : Smad8 Protein, MESH : Bone Morphogenetic Protein 6, MESH: Liver
Abstract: Although hepcidin expression was shown to be induced by the BMP/Smad signaling pathway, it is not yet known how iron regulates this pathway and what its exact molecular targets are. We therefore assessed genome-wide liver transcription profiles of mice of 2 genetic backgrounds fed iron-deficient, -balanced, or -enriched diets. Among 1419 transcripts significantly modulated by the dietary iron content, 4 were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, Smad7, Id1, and Atoh8 all related to the Bmp/Smad pathway. As shown by Western blot analysis, variations in Bmp6 expression induced by the diet iron content have for functional consequence similar changes in Smad1/5/8 phosphorylation that leads to formation of heteromeric complexes with Smad4 and their translocation to the nucleus. Gene expression variations induced by secondary iron deficiency or iron overload were compared with those consecutive to Smad4 and Hamp1 deficiency. Iron overload developed by Smad4- and Hamp1-deficient mice also increased Bmp6 transcription. However, as shown by analysis of mice with liver-specific disruption of Smad4, activation of Smad7, Id1, and Atoh8 transcription by iron requires Smad4. This study points out molecules that appear to play a critical role in the control of systemic iron balance.
Published: 2008
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34. The beta-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules

Author: Charles Auffray, Paulette Bioulac-Sage, Sandrine Imbeaud, Louis Libbrecht, Sandra Rebouissou, Jessica Zucman-Rossi, Gabrielle Couchy, Charles Balabaud, Tania Roskams, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Liver Research Unit of the Laboratory of Morphology and Molecular Pathology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Genexpress, Génomique Fonctionnelle et Biologie Systémique pour la Santé, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Inserm (Réseaux de recherche clinique et réseaux de recherche en santé des populations), the comité Dordogne de la Ligue contre le Cancer, the SNFGE and the program 'Carte d'identité des tumeurs' by the ligue Nationale Contre le Cancer. SR is supported by a Ligue Nationale Contre le Cancer doctoral fellowship., Zucman-Rossi, Jessica, Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Catholic University of Leuven ( KU Leuven ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de génétique moléculaire ( CGM ), and Centre National de la Recherche Scientifique ( CNRS )
Subjects: Liver Cirrhosis, Male, Pathology, MESH : Liver Neoplasms, MESH : RNA, Messenger, Cirrhosis, MESH: Focal Nodular Hyperplasia, MESH: beta Catenin, MESH : Aged, ß-catenin, MESH: Down-Regulation, Benign tumor, MESH : Down-Regulation, Transcriptome, 0302 clinical medicine, zonation, benign tumor, MESH: Liver Neoplasms, MESH: Reverse Transcriptase Polymerase Chain Reaction, Focal nodular hyperplasia, MESH: Up-Regulation, MESH : Female, MESH: Carcinoma, Hepatocellular, MESH : Up-Regulation, beta Catenin, MESH: Aged, Alpha 1-antitrypsin deficiency, MESH: Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Liver Neoplasms, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Extracellular Matrix, glutamine synthetase, MESH : Adult, Middle Aged, Extracellular Matrix, Up-Regulation, 030220 oncology & carcinogenesis, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Female, 030211 gastroenterology & hepatology, MESH: Liver Cirrhosis, microarray, MESH : Carcinoma, Hepatocellular, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, MESH : Male, Down-Regulation, Biology, MESH: Extracellular Matrix, Biological pathway, 03 medical and health sciences, MESH: Gene Expression Profiling, medicine, MESH : Liver Cirrhosis, Humans, MESH : Middle Aged, RNA, Messenger, Aged, MESH: RNA, Messenger, MESH: Humans, Hepatology, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular adenoma, MESH : beta Catenin, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Gene expression profiling, diagnostic markers, MESH : Focal Nodular Hyperplasia, Cancer research, transcriptome, MESH: Female
Abstract: International audience; BACKGROUND/AIMS: Focal nodular hyperplasias (FNHs) are benign liver lesions considered to be a hyperplastic response to increased blood flow in normal liver. In contrast, FNH-like lesions/nodules occur in cirrhotic liver but share similar histopathological features. We conducted a transcriptome analysis to identify biological pathways deregulated in FNH. METHODS: Gene expression profiles obtained in FNH and normal livers were compared. Differentially-expressed genes were validated using quantitative-RT-PCR in 70 benign liver tumors including FNH-like lesions. RESULTS: Among the deregulated genes in FNHs, 19 displayed physiological restricted distribution in the normal liver. All six perivenous genes were up-regulated in FNH, whereas 13 periportal genes were down-regulated. Almost all these genes are known to be regulated by beta-catenin. Glutamine synthetase was markedly overexpressed in anastomosed areas usually centered on visible veins. Moreover, activated hypophosphorylated beta-catenin protein accumulated in FNH in the absence of activating mutations. These results suggest the zonated activation of the beta-catenin pathway in FNH, whereas the other benign hepatocellular tumors, including FNH-like lesions, demonstrated an entirely different pattern of beta-catenin expression. CONCLUSIONS: In FNH, increased activation of the beta-catenin pathway was found restricted to enlarged perivenous areas. FNH-like nodules may have a different pathogenetic origin.
Published: 2008
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35. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. : hepatocellular tumors miRNA profiling

Author: Ladeiro , Yannick, Couchy , Gabrielle, Balabaud , Charles, Bioulac-Sage , Paulette, Pelletier , Laura, Rebouissou , Sandra, Zucman-Rossi , Jessica, Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, and This work was supported by the ANRS, Inserm (Réseaux de recherche clinique et réseaux de recherche en santé des populations), and the program 'Carte d'identité des tumeurs' initiated, developed and funded by the Ligue Nationale Contre le Cancer. YL is supported by an ANRS doctoral fellowship. JZR is supported by a 'contrat d'interface' between Inserm and CHU Bordeaux.
Subjects: MESH : Carcinoma, Hepatocellular, MESH : Liver Neoplasms, Hepatocellular carcinoma, MESH : Gene Expression Regulation, Neoplastic, MESH : Genes, Tumor Suppressor, ß-catenin, Benign and malignant tumors, liver cell adenoma, MESH : Tumor Cells, Cultured, Focal nodular hyperplasia, HBV, Alcohol consumption, miRNA, MESH : Gene Expression Profiling, MESH : Humans, biomarkers, MESH : beta Catenin, Hepatocellular adenoma, MESH : Risk Factors, HNF1a, MESH : MicroRNAs, MESH : Phenotype, HCV, MESH : Hepatocyte Nuclear Factor 1-alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Mutation, microarray, transcriptome
Abstract: International audience; Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1alpha and beta-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of beta-catenin-targeted genes as miR-107 expression was correlated to that of HNF1alpha in a small interfering RNA cell line model. Thus, this strongly suggests that beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively. CONCLUSION: Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations. Dissecting these relationships provides a new hypothesis to understand the functional impact of miRNA deregulation in liver tumorigenesis and the promising use of miRNAs as diagnostic markers.
Published: 2008
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36. Listeria monocytogenes EGD-e biofilms: no mushrooms but a network of knitted chains

Author: Aurélie Rieu, Romain Briandet, Olivier Habimana, Jean Guzzo, Dominique Garmyn, Pascal Piveteau, Laboratoire de Recherche en Vigne et Vin (REVV), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Bioadhésion et Hygiène des Matériaux (BHM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Microbiologie du Sol et de l'Environnement (MSE), 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-Université de Bourgogne (UB), Laboratoire de Recherche en Vigne et Vin ( REVV ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Bioadhésion et Hygiène des Matériaux ( BHM ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Microbiologie du Sol et de l'Environnement ( MSE ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB )
Subjects: Image Processing, MESH : Analysis of Variance, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Green Fluorescent Proteins, medicine.disease_cause, MESH: Listeria monocytogenes, Applied Microbiology and Biotechnology, Bacterial Adhesion, law.invention, Green fluorescent protein, Plasmid, Computer-Assisted, law, Genes, Reporter, Image Processing, Computer-Assisted, MESH : Bacterial Proteins, MESH: Microscopy, Confocal, Pathogen, MESH: Bacterial Proteins, 2. Zero hunger, 0303 health sciences, Microscopy, Microscopy, Confocal, Photobleaching, Ecology, biology, MESH: Kinetics, MESH : Genes, Reporter, MESH: Image Processing, Computer-Assisted, MESH : Biofilms, Confocal, MESH : Kinetics, MESH: Photobleaching, MESH : Image Processing, Computer-Assisted, Biotechnology, Plasmids, MESH : Bacterial Adhesion, Green Fluorescent Proteins, MESH: Biofilms, MESH : Photobleaching, Microbiology, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Green Fluorescent Proteins, Listeria monocytogenes, Bacterial Proteins, Confocal microscopy, MESH: Plasmids, MESH: Analysis of Variance, medicine, MESH: Bacterial Adhesion, MESH : Microscopy, Confocal, Reporter, 030304 developmental biology, Analysis of Variance, 030306 microbiology, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH: Genes, Reporter, Biofilm, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Culture Media, Kinetics, Genes, MESH : Plasmids, Biofilms, MESH: Culture Media, Food Microbiology, MESH : Culture Media, MESH : Listeria monocytogenes, Bacteria, Food Science
Abstract: Listeria monocytogenes is a food pathogen that can attach on most of the surfaces encountered in the food industry. Biofilms are three-dimensional microbial structures that facilitate the persistence of pathogens on surfaces, their resistance toward antimicrobials, and the final contamination of processed goods. So far, little is known about the structural dynamics of L. monocytogenes biofilm formation and its regulation. The aims of this study were, by combining genetics and time-lapse laser-scanning confocal microscopy (LSCM), (i) to characterize the structural dynamics of L. monocytogenes EGD-e sessile growth in two nutritional environments (with or without a nutrient flow), and (ii) to evaluate the possible role of the L. monocytogenes agr system during biofilm formation by tracking the spatiotemporal fluorescence expression of a green fluorescent protein (GFP) reporter system. In the absence of nutrient flow (static conditions), unstructured biofilms composed of a few layers of cells that covered the substratum were observed. In contrast, when grown under dynamic conditions, L. monocytogenes EGD-e biofilms were highly organized. Indeed, ball-shaped microcolonies were surrounded by a network of knitted chains. The spatiotemporal tracking of fluorescence emitted by the GFP reporter system revealed that agr expression was barely detectable under static conditions, but it progressively increased during 40 h under dynamic conditions. Moreover, spatial analysis revealed that agr was expressed preferentially in cells located outside the microcolonies. Finally, the in-frame deletion of agrA , which encodes a transcriptional regulator, resulted in a decrease in initial adherence without affecting the subsequent biofilm development.
Published: 2008
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37. Transforming growth factor beta controls the directional migration of hepatocyte cohorts by modulating their adhesion to fibronectin

Author: Urszula Hibner, Fabien Binamé, Patrice Lassus, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: rac1 GTP-Binding Protein, MESH : Cell Line, MESH : Protein Subunits, Apoptosis, Cell Communication, Integrin alpha5, MESH : Hepatocytes, Epithelium, Mesoderm, MESH: Hepatocytes, Mice, 0302 clinical medicine, Cell Movement, Transforming Growth Factor beta, MESH: Fibronectins, MESH : Cell Movement, MESH : Fibronectins, MESH: Animals, MESH: Cell Movement, MESH: Mesoderm, 0303 health sciences, MESH : Gene Expression Regulation, MESH: Cell Surface Extensions, MESH : Mesoderm, Articles, Adhesion, MESH: Protein Subunits, MESH: Gene Expression Regulation, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hepatocyte, MESH: Integrin alpha5, MESH : Cell Communication, MESH : Cell Membrane, MESH : Cell Surface Extensions, Biology, Cell Line, MESH: Cell Adhesion, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : rac1 GTP-Binding Protein, MESH : Integrin alpha5, MESH: Cell Communication, MESH : Mice, Cell Adhesion, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: Humans, MESH: rac1 GTP-Binding Protein, Gene Expression Profiling, MESH: Apoptosis, MESH : Gene Expression Profiling, Cell Membrane, MESH : Humans, Cell Biology, MESH : Epithelium, Fibronectins, MESH: Cell Line, Fibronectin, Protein Subunits, MESH: Epithelium, MESH : Cell Adhesion, MESH : Transforming Growth Factor beta, Gene Expression Regulation, Hepatocytes, biology.protein, Cell Surface Extensions, MESH : Animals, MESH : Apoptosis, MESH: Cell Membrane, Transforming growth factor
Abstract: International audience; Transforming growth factor beta (TGF-beta) has a strong impact on liver development and physiopathology, exercised through its pleiotropic effects on growth, differentiation, survival, and migration. When exposed to TGF-beta, the mhAT3F cells, immortalized, highly differentiated hepatocytes, maintained their epithelial morphology and underwent dramatic alterations of adhesion, leading to partial or complete detachment from a culture plate, followed by readhesion and spreading. These alterations of adhesive behavior were caused by sequential changes in expression of the alpha5beta1 integrin and of its ligand, the fibronectin. The altered specificity of anchorage to the extracellular matrix gave rise to changes in cells' collective motility: cohorts adhering to fibronectin maintained a persistent, directional motility, with ezrin-rich pathfinder cells protruding from the tips of the cohorts. The absence of adhesion to fibronectin prevented the appearance of polarized pathfinders and lead to random, oscillatory motility. Our data suggest a novel role for TGF-beta in the control of collective migration of epithelial cohorts.
Published: 2008
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38. Advances in environmental genomics: towards an integrated view of micro-organisms and ecosystems

Author: Philippe Normand, Philippe N. Bertin, Claudine Médigue, 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), Structure et évolution des génomes (SEG), CNS-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), 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 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), 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), 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 ), Structure et évolution des génomes ( SEG ), CNS-Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -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 ), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), 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, 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), Génomique métabolique ( UMR 8030 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: Proteomics, MESH: Sequence Analysis, DNA, MESH : Proteomics, Microbial, MESH : Ecosystem, Environmental Microbiology, MESH: Ecosystem, 0303 health sciences, Ecology, MESH: Protein Array Analysis, MESH: Genomics, MESH: Proteomics, MESH: Environmental Microbiology, MESH : Protein Array Analysis, Genomics, MESH: Genetics, Microbial, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Sequence Analysis, Genetics, Microbial, Protein Array Analysis, Computational biology, Biology, MESH : Genetics, Microbial, Microbiology, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Ecosystem, MESH : Bacteria, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Ecological niche, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Bacteria, 030306 microbiology, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Genomics, Sequence Analysis, DNA, DNA, MESH : Environmental Microbiology, MESH: Bacteria, Metagenomics, Mrna profiling, Microbial genome, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, MESH : Sequence Analysis, DNA
Abstract: International audience; Microbial genome sequencing has, for the first time, made accessible all the components needed for both the elaboration and the functioning of a cell. Associated with other global methods such as protein and mRNA profiling, genomics has considerably extended our knowledge of physiological processes and their diversity not only in human, animal and plant pathogens but also in environmental isolates. At a higher level of complexity, the so-called meta approaches have recently shown great promise in investigating microbial communities, including uncultured micro-organisms. Combined with classical methods of physico-chemistry and microbiology, these endeavours should provide us with an integrated view of how micro-organisms adapt to particular ecological niches and participate in the dynamics of ecosystems.
Published: 2008
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39. A novel nonsymbiotic hemoglobin from oak: cellular and tissue specificity of gene expression

Author: Audrey Berger, James F. Dat, Pierre-Marie Badot, Hélène Folzer, Nicolas Capelli, Michèle Crèvecoeur, Claire Parent, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Département de Botanique et Biologie Végétale, Université de Genève ( UNIGE ), Institut Méditerranéen d'Ecologie et de Paléoécologie ( IMEP ), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Genève (UNIGE), Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Centre National de la Recherche Scientifique (CNRS)-Avignon Université (AU)-Université de Provence - Aix-Marseille 1, Laboratoire Chrono-environnement (UMR 6249) (LCE), Université de Genève = University of Geneva (UNIGE), and Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, MESH : Molecular Sequence Data, MESH : Oxygen, Physiology, MESH: Plant Shoots, MESH : Plant Roots, MESH: Plant Roots, Plant Science, MESH: Amino Acid Sequence, MESH: RNA, Plant, MESH : Hemoglobins, 01 natural sciences, Plant Roots, Hemoglobins, Quercus, Gene Expression Regulation, Plant, Gene expression, Cloning, Molecular, Hypoxia, MESH: Phylogeny, Peptide sequence, Phylogeny, MESH: Organ Specificity, Plant Proteins, 0303 health sciences, Oak (Quercus petraea, Quercus robur), MESH: Plant Proteins, MESH : Amino Acid Sequence, MESH : In Situ Hybridization, nonsymbiotic hemoglobin, MESH : Plant Shoots, MESH : Water, ddc:580, MESH: Hemoglobins, Organ Specificity, RNA, Plant, Quercus petraea, oak (Quercus petraea, In situ hybridization, Quercus robur), Plant Shoots, MESH: Oxygen, MESH : Cloning, Molecular, Molecular Sequence Data, education, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Quercus robur, MESH : Organ Specificity, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: In Situ Hybridization, ddc:570, MESH: Quercus, MESH : Plant Proteins, Botany, MESH: Water, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MESH: Cloning, Molecular, Northern blot, Amino Acid Sequence, MESH: Gene Expression Regulation, Plant, Gene, 030304 developmental biology, MESH: Molecular Sequence Data, hypoxia, MESH : RNA, Plant, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Gene Expression Profiling, MESH : Gene Expression Profiling, Water, MESH : Phylogeny, Meristem, biology.organism_classification, Molecular biology, Oxygen, Nonsymbiotic hemoglobin, gene expression, in situ hybridization, MESH : Quercus, MESH : Gene Expression Regulation, Plant, 010606 plant biology & botany
Abstract: International audience; This study presents the isolation and characterization of a novel nonsymbiotic Hb gene from sessile oak (Quercus petraea) seedlings, herein designated QpHb1. The cellular and tissue expression of QpHb1 was analysed by Northern blotting and in situ hybridization. The encoded protein was predicted to consist of 161 amino acid residues, and shares 71 and 51% amino acid sequence identity with the Arabidopsis class 1 and 2 nonsymbiotic Hb, respectively. Northern blot analysis revealed that QpHb1 was strongly expressed in roots. Spatial expression analysis of QpHb1 in the root apical region of sessile oak by in situ hybridization indicated that transcripts were mostly abundant in protoxylem cell initials, some cortical cells and the protoderm. In addition, when comparing the expression profile of QpHb1 in sessile and pedunculate oak (Quercus robur), two species with contrasted hypoxia tolerance, the transcript level of QpHb1 rose early in the most flood-tolerant species, pedunculate oak, during root submergence. The spatial-temporal expression of QpHb1 suggests that this gene could participate in perception and signalling during hypoxia.
Published: 2008
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40. PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

Author: José Palacios, Amparo Cano, Amandine Cartier-Michaud, Gema Moreno-Bueno, Elizabeth Fabre-Guillevin, Benoît Vallée, Michel Malo, Georgia Barlovatz-Meimon, Daniel A. Lawrence, Héctor Peinado, Cécile Charrière-Bertrand, Hôpital Européen Georges Pompidou [APHP] (HEGP), DYNAMIC, Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS), Centre National d'Investigations Oncologiques (CNIO), CNIO, Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Centre National de la Recherche Scientifique (CNRS), Servicio de Anatomia Patologica, Hospital Virgen del Rocío, Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Spanish National Cancer Research Center (CNIO), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario Virgen del Rocío [Sevilla], and Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Wound Healing, Fluorescent Antibody Technique, Snail, MESH : Breast Neoplasms, MESH: Cadherins, MESH: Plasminogen Activator Inhibitor 1, Metastasis, Immunoenzyme Techniques, chemistry.chemical_compound, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Cell Movement, MESH: Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, MESH : Cell Movement, MESH : Female, Pseudopodia, Receptor, MESH: Cell Movement, MESH: Fluorescent Antibody Technique, Genes, Dominant, Oligonucleotide Array Sequence Analysis, Medicine(all), 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Cell migration, MESH : Urokinase-Type Plasminogen Activator, MESH: Transcription Factors, MESH : Genes, Dominant, Cadherins, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, 030220 oncology & carcinogenesis, Plasminogen activator inhibitor-1, Female, MESH : Cadherins, Research Article, MESH : Plasminogen Activator Inhibitor 1, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Urokinase-Type Plasminogen Activator, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : Immunoenzyme Techniques, biology.animal, Plasminogen Activator Inhibitor 1, medicine, Humans, RNA, Messenger, MESH: Tumor Cells, Cultured, MESH: Immunoenzyme Techniques, Cell adhesion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: RNA, Messenger, 030304 developmental biology, Wound Healing, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, Cancer, medicine.disease, Urokinase-Type Plasminogen Activator, Molecular biology, MESH: Wound Healing, MESH : Fluorescent Antibody Technique, chemistry, MESH: Pseudopodia, MESH: Oligonucleotide Array Sequence Analysis, SNAI1, MESH : Pseudopodia, Cancer research, Snail Family Transcription Factors, MESH: Genes, Dominant, MESH: Female, MESH: Breast Neoplasms, Transcription Factors
Abstract: International audience; INTRODUCTION: Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation (PA) system, including urokinase plasminogen activator (uPA), its receptor and its inhibitor, plasminogen activator inhibitor type 1(PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non-proteolytic modulation of cell adhesion and migration. Thus, Snail and the PA system are both over-expressed in cancer and influence this process. In this study we aimed to determine if the activity of SNAI1 (a member of the Snail family) is correlated with expression of the PA system components and how this correlation can influence tumoural cell migration. METHODS: We compared the invasive breast cancer cell-line MDA-MB-231 expressing SNAI1 (MDA-mock) with its derived clone expressing a dominant-negative form of SNAI1 (SNAI1-DN). Expression of PA system mRNAs was analysed by cDNA microarrays and real-time quantitative RT-PCR. Wound healing assays were used to determine cell migration. PAI-1 distribution was assessed by immunostaining. RESULTS: We demonstrated by both cDNA microarrays and real-time quantitative RT-PCR that the functional blockade of SNAI1 induces a significant decrease of PAI-1 and uPA transcripts. After performing an in vitro wound-healing assay, we observed that SNAI1-DN cells migrate more slowly than MDA-mock cells and in a more collective manner. The blockade of SNAI1 activity resulted in the redistribution of PAI-1 in SNAI1-DN cells decorating large lamellipodia, which are commonly found structures in these cells. CONCLUSIONS: In the absence of functional SNAI1, the expression of PAI-1 transcripts is decreased, although the protein is redistributed at the leading edge of migrating cells in a manner comparable with that seen in normal epithelial cells.
Published: 2008
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41. Regulation of inflammation-related genes in human adipose tissue

Author: Dominique Langin, Karine Clément, Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital de l'Hôtel-Dieu, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH: Inflammation, Panniculitis, Adipose tissue, MESH : Panniculitis, 0302 clinical medicine, Weight loss, Macrophage, Medicine, MESH: Obesity, MESH : Macrophages, MESH : Tumor Necrosis Factor-alpha, 0303 health sciences, MESH : Gene Expression Regulation, MESH: Panniculitis, MESH: Gene Expression Regulation, 3. Good health, Adipose Tissue, MESH : Obesity, medicine.symptom, Inflammation Mediators, MESH: Adipose Tissue, Calorie restriction, MESH: Inflammation Mediators, 030209 endocrinology & metabolism, Inflammation, Context (language use), Physical exercise, MESH : Adipose Tissue, MESH : Inflammation Mediators, 03 medical and health sciences, MESH: Gene Expression Profiling, Internal Medicine, Humans, Serum amyloid A, Obesity, 030304 developmental biology, MESH : Inflammation, MESH: Humans, business.industry, Tumor Necrosis Factor-alpha, MESH : Gene Expression Profiling, Gene Expression Profiling, Macrophages, MESH : Humans, MESH: Macrophages, Gene Expression Regulation, MESH: Tumor Necrosis Factor-alpha, Immunology, business
Abstract: International audience; The identification of a moderate increase in circulating inflammatory factors in obese subjects, the description of changes in inflammatory gene expression in adipose tissue (AT) and the discovery that macrophage cells infiltrate AT are observations contributing to the concept that human obesity is a chronic inflammatory illness. This concept has led to some revision of the physiopathology of obesity and of its related metabolic and cardiovascular co-morbidities. Low-grade inflammation in the AT and the subsequent production of specific biomarkers could actually link expanded fat mass to obesity complications. This review aims at providing an overview of the current knowledge brought up by human gene expression studies, notably those performed on a large scale in AT depots. The regulation of specific biomarkers related to inflammation and putative new candidates (i.e. cathepsins and serum amyloid A) is discussed in the context of weight loss programmes based on calorie restriction and physical exercise. The foreseen clinical and technological challenges are also summarized.
Published: 2007
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42. Tumor genomic profiling and TP53 germline mutation analysis of first-degree relative familial gliomas

Author: Blandine Boisselier, Catherine Carpentier, Sophie Paris, Florence Laigle-Donadey, Khê Hoang-Xuan, Jean-Yves Delattre, Yannick Marie, Karima Mokhtari, Olivier Delattre, Emmanuelle Crinière, Michèle Kujas, Stéphane Liva, Ahmed Idbaih, Marc Sanson, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Bioinformatique (CURIE-BIOINFO), Institut Curie [Paris], Laboratoire de Neuropathologie Raymond Escourolle, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Bioinformatique ( CURIE-BIOINFO ), INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Idbaih, Ahmed, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, Cancer Research, MESH : Germ-Line Mutation, DNA Mutational Analysis, MESH : Aged, MESH: Genes, p53, [SDV.GEN] Life Sciences [q-bio]/Genetics, Allelic Imbalance, MESH: Base Sequence, Germline, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Glioma, 0302 clinical medicine, MESH: Germ-Line Mutation, MESH : Female, MESH: DNA Mutational Analysis, Genetics, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Brain Neoplasms, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Glioma, MESH : Adult, Middle Aged, 3. Good health, Pedigree, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adult, MESH: Pedigree, MESH : Male, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : DNA Mutational Analysis, Biology, MESH : Genes, p53, Polymorphism, Single Nucleotide, 03 medical and health sciences, MESH: Gene Expression Profiling, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, MESH : Middle Aged, Family, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Allele, MESH : Brain Neoplasms, Molecular Biology, MESH : Allelic Imbalance, neoplasms, MESH: Family, Germ-Line Mutation, 030304 developmental biology, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Base Sequence, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, MESH: Allelic Imbalance, Chromosome, MESH: Adult, medicine.disease, Genes, p53, MESH: Male, Gene expression profiling, MESH : Glioma, MESH : Pedigree, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Base Sequence, MESH : Family, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female, Comparative genomic hybridization
Abstract: International audience; About 5% of gliomas occur in a familial context, which suggests a genetic origin, but the predisposing molecular factors remain unknown in most cases. A series of nine familial gliomas were characterized with 1-megabase resolution BAC array-based comparative genomic hybridization (aCGH) together with germline sequence analysis of TP53. This series was compared with a literature series of familial gliomas and a personal series of sporadic gliomas, analyzed by chromosome CGH and aCGH, respectively. No significant difference was noted between the three populations in terms of clinical characteristics, pathologic features, and the most frequent chromosomal alterations, including loss of 1p, 10p, 10q, 13q, and 19q, and gain of 7p, 7q, 16p, 18q, 19p, 19q, 20p, and 22q. However, a genomic region located in 6q was more frequently gained in our series of familial as compared to sporadic gliomas (P=0.028). A germline TP53 mutation was observed in 1/9 cases, which suggests Li-Fraumeni syndrome. Interestingly, the Pro allele in the codon 72 of TP53 was observed in 5/9 tumors. Although familial and sporadic gliomas share very similar cytogenetic quantitative patterns, aCGH is a promising technique for the detection of small genomic differences of potential significance.
Published: 2007
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43. HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation

Author: Sandrine Imbeaud, Justine Bertrand-Michel, Sandra Rebouissou, Charles Auffray, Charles Balabaud, François Tercé, Paulette Bioulac-Sage, Virginie Boulanger, Jessica Zucman-Rossi, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex Immuno-oncology, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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)-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)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, This work was supported by the Inserm (Réseau de Recherche clinique et en santé des populations), ARC n°5188, SNFGE and the Fondation de France. SR is supported by a Ligue Nationale Contre le Cancer doctoral fellowship., Zucman-Rossi, Jessica, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs ( LGMNPN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateau de lipidomique, Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Claude de Preval
Subjects: Male, Biochemistry, 0302 clinical medicine, MESH: Liver Neoplasms, Glycolysis, MESH : Glycolysis, Oligonucleotide Array Sequence Analysis, chemistry.chemical_classification, 0303 health sciences, MESH: Middle Aged, Fatty Acids, Liver Neoplasms, MESH: SREBP-1, MESH: Transcription Factors, Gene Expression Regulation, Neoplastic, MESH : Oligonucleotide Array Sequence Analysis, MESH: Promoter Regions (Genetics), 030220 oncology & carcinogenesis, MESH : Hepatocyte Nuclear Factor 1-alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sterol Regulatory Element Binding Protein 1, MESH: Citric Acid, MESH : Gene Expression Regulation, Neoplastic, Adenoma, Liver Cell, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Sterol Regulatory Element Binding Protein 1, MESH : steatosis, MESH : Adenoma, Liver Cell, MESH : Sterol Regulatory Element Binding Protein 1, MESH : Adolescent, Humans, MESH : Middle Aged, MESH: Hepatocyte Nuclear Factor 1-alpha, Molecular Biology, Fatty acid synthesis, MESH: Lipogenesis, MESH: Adolescent, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, Fatty acid, MESH : HNF1α, MESH: Adult, medicine.disease, MESH : Promoter Regions (Genetics), Sterol regulatory element-binding protein, chemistry, MESH: Tumor Markers, Biological, MESH : Response Elements, MESH: Female, Transcription Factors, MESH: Liver, MESH: Signal Transduction, MESH : Liver Neoplasms, MESH : Fatty Liver, MESH : Transcription Factors, chemistry.chemical_compound, MESH: Adenoma, Liver Cell, MESH : Tumor Markers, Biological, MESH : Female, Hepatocyte Nuclear Factor 1-alpha, Promoter Regions, Genetic, MESH : Fatty Acids, MESH: Fatty Liver, MESH: Gluconeogenesis, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, MESH : Adult, MESH: Fatty Acids, Liver, Lipogenesis, MESH: Glycolysis, Female, MESH: Response Elements, MESH : SREBP-1, Signal Transduction, Adult, Adolescent, MESH : Male, MESH : Gluconeogenesis, MESH : Citric Acid, Biology, Response Elements, Citric Acid, MESH: steatosis, Biomarkers, Tumor, medicine, MESH : hepatocellular adenoma, Carbohydrate-responsive element-binding protein, Transcription factor, 030304 developmental biology, MESH : Signal Transduction, Gene Expression Profiling, MESH: hepatocellular adenoma, Gluconeogenesis, MESH : Liver, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, MESH: HNF1α, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH : Lipogenesis, Fatty Liver, MESH: Oligonucleotide Array Sequence Analysis, Steatosis
Abstract: International audience; Biallelic inactivating mutations of the transcription factor 1 gene (TCF1), encoding hepatocyte nuclear factor 1alpha (HNF1alpha) were identified in 50% of hepatocellular adenomas (HCA) phenotypically characterized by a striking steatosis. To understand the molecular basis of this aberrant lipid storage, we performed a microarray transcriptome analysis validated by quantitative reverse transcription-PCR, Western blotting, and lipid profiling. In mutated HCA, we showed a repression of gluconeogenesis coordinated with an activation of glycolysis, citrate shuttle, and fatty acid synthesis predicting elevated rates of lipogenesis. Moreover, the strong down-regulation of liver fatty acid-binding protein suggests that impaired fatty acid trafficking may also contribute to the fatty phenotype. In addition, transcriptional profile analysis of the observed deregulated genes in non-HNF1alpha-mutated HCA as well as in non-tumor livers allowed us to define a specific signature of the HNF1alpha-mutated HCA. In these tumors, lipid composition was dramatically modified according to the transcriptional deregulations identified in the fatty acid synthetic pathway. Surprisingly, lipogenesis activation did not operate through sterol regulatory element-binding protein-1 (SREBP-1) and carbohydrate-response element-binding protein (ChREBP) that were repressed. We conclude that steatosis in HNF1alpha-mutated HCA results mainly from an aberrant promotion of lipogenesis that is linked to HNF1alpha inactivation and that is independent of both SREBP-1 and ChREBP activation. Finally, our findings have potential clinical implications since lipogenesis can be efficiently inhibited by targeted therapies.
Published: 2007
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44. Analysis of transcriptional responses in the mouse dorsal striatum following acute 3,4-methylenedioxymethamphetamine (ecstasy): identification of extracellular signal-regulated kinase-controlled genes

Author: Cynthia Marie-Claire, Corinne Canestrelli, Florence Noble, Julie Salzmann, Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique (NAVVEC - UM 81 (UMR 8206/ U705)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Diderot - Paris 7 (UPD7), Consortium National de Recherche en Génomique (CNRG) 4999, Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique ( NAVVEC (UM 81) ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Marie-Claire, Cynthia, Université Paris Diderot - Paris 7 (UPD7)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MAPK/ERK pathway, Male, MESH: Signal Transduction, MESH : RNA, Messenger, MESH: Cytoskeletal Proteins, MESH: Neurons, MESH: Hallucinogens, Mice, 0302 clinical medicine, Gene expression, MESH: Up-Regulation, MESH : Trans-Activation (Genetics), MESH : Neuronal Plasticity, MESH: Animals, MESH: Nerve Tissue Proteins, MESH: Neuronal Plasticity, Extracellular Signal-Regulated MAP Kinases, MESH : Nerve Tissue Proteins, MESH : Up-Regulation, MESH: Extracellular Signal-Regulated MAP Kinases, Oligonucleotide Array Sequence Analysis, Neurons, 0303 health sciences, Neuronal Plasticity, Kinase, General Neuroscience, MESH: Gene Expression Regulation, Enzymologic, MESH : Extracellular Signal-Regulated MAP Kinases, Cell biology, Up-Regulation, MESH : Oligonucleotide Array Sequence Analysis, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Signal transduction, Intracellular, psychological phenomena and processes, Signal Transduction, Transcriptional Activation, MESH: Enzyme Activation, MESH : Neostriatum, MESH : Male, N-Methyl-3,4-methylenedioxyamphetamine, Nerve Tissue Proteins, Biology, MESH : Neurons, Article, Gene Expression Regulation, Enzymologic, MESH : Gene Expression Regulation, Enzymologic, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Mice, mental disorders, Extracellular, Animals, RNA, Messenger, MESH : N-Methyl-3,4-methylenedioxyamphetamine, Transcription factor, MESH: Mice, Protein kinase C, 030304 developmental biology, MESH: RNA, Messenger, MESH : Signal Transduction, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Cytoskeletal Proteins, MESH : Hallucinogens, Molecular biology, MESH: Male, Enzyme Activation, Neostriatum, Cytoskeletal Proteins, MESH: Neostriatum, MESH: Trans-Activation (Genetics), MESH: Oligonucleotide Array Sequence Analysis, Hallucinogens, MESH: N-Methyl-3,4-methylenedioxyamphetamine, MESH : Animals, MESH : Enzyme Activation, 030217 neurology & neurosurgery
Abstract: International audience; 3,4-Methylenedioxymethamphetamine (ecstasy), a widely used recreational drug with psychoactive properties, induces both serotonin and dopamine release in the brain. However, little is known about its intracellular effects. We previously showed that 3,4-methylenedioxymethamphetamine rewarding effects in mice were dependent upon extracellular signal-regulated kinase activation and that dorsal striatum was a critical region for mediating extracellular signal-regulated kinase-dependent Egr1 3,4-methylenedioxymethamphetamine-induced transcription. Here, we extend these findings by showing that 3,4-methylenedioxymethamphetamine is indeed able to activate extracellular signal-regulated kinase within this structure. To identify genes regulated by acute 3,4-methylenedioxymethamphetamine in the mice dorsal striatum, and selectively controlled by this kinase, we performed microarray experiments by using a selective inhibitor of extracellular signal-regulated kinase activation, SL327. Of the approximately 24,000 genes from the microarray, 27 showed altered expression after exposure to 3,4-methylenedioxymethamphetamine, and among these, 59% were partially or totally inhibited by SL327 pretreatment. Our results showed that the genes regulated by 3,4-methylenedioxymethamphetamine encode proteins that belong to transcription factors family, signaling pathways (phosphatases, cytoskeleton regulation), and synaptic functions. These early changes, and especially those controlled by extracellular signal-regulated kinase activation might play significant roles in the expression of many of the behaviors that occur following 3,4-methylenedioxymethamphetamine taking.
Published: 2006
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45. Proteomic characterization of the acid tolerance response in Lactococcus lactis MG1363

Author: Aurélie Budin-Verneuil, Yanick Auffray, Vianney Pichereau, Dusko Ehrlich, Emmanuelle Maguin, Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-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, Laboratoire de Microbiologie de l’Environnement (LME), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Unité de recherche Génétique Microbienne (UGM), Institut National de la Recherche Agronomique (INRA), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Unité de Recherche Risques Microbiens ( U2RM ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Laboratoire des Sciences de l'Environnement Marin (LEMAR) ( LEMAR ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Brest ( UBO ) -Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ) -Institut Universitaire Européen de la Mer ( IUEM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université de Brest ( UBO ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université de Brest ( UBO ) -Institut de Recherche pour le Développement ( IRD ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), and Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech
Subjects: MESH: Hydrogen-Ion Concentration, Hot Temperature, Proteome, [SDV]Life Sciences [q-bio], ELECTROPHORESE 2-DIMENSIONS, Proteomics, Biochemistry, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, LACTIC ACID BACTERIA, MESH : Bacterial Proteins, Electrophoresis, Gel, Two-Dimensional, MESH: Bacterial Proteins, MESH : Adaptation, Physiological, 0303 health sciences, Lactococcus lactis I, Hydrogen-Ion Concentration, Adaptation, Physiological, Lactococcus lactis, MESH: Proteome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Hot Temperature, acid tolerance response, HEAT SHOCK, MESH : Proteome, Biology, MESH: Hot Temperature, TRANSCRIPTIONAL ANALYSIS, 03 medical and health sciences, MESH: Gene Expression Profiling, Bacterial Proteins, Downregulation and upregulation, MESH : Hydrogen-Ion Concentration, Molecular Biology, Gene, 030304 developmental biology, Two-dimensional gel electrophoresis, 030306 microbiology, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Electrophoresis, Gel, Two-Dimensional, Metabolism, biology.organism_classification, MESH: Electrophoresis, Gel, Two-Dimensional, TWO-DIMENSIONAL ELECTROPHORESIS, Molecular biology, MESH: Adaptation, Physiological, Culture Media, ACID STRESS RESPONSE, De novo synthesis, MESH: Lactococcus lactis, MESH: Culture Media, MESH : Culture Media, MESH : Lactococcus lactis, Bacteria
Abstract: International audience; Exponentially growing cells of Lactococcus lactis MG1363 are able to develop an Acid Tolerance Response (ATR) when incubated at pH 5, in both rich (M17)--and chemically defined (SA)--culture media. Physiological and proteomic characterization of this adaptive response indicated that L. lactis reorganizes its metabolism in response to acid stress to a great extent and quite differently in the two media. The development of ATR was fully dependent on protein de novo synthesis in SA and only partly dependent in M17. 2D gel electrophoresis revealed a total of 90 spots induced by acidity, 80 of which were identified by mass spectrometry. Only 10 proteins (BglA, PycA, GlmS, HasC, ArgS, GatA, AtpA, ArcB, Cfa, and SodA) were overproduced in the two media. A transcriptional analysis of the corresponding genes suggested that for half of them the mode of regulation may differ in the two media. Among the protein spots upregulated during the ATR in SA but not in M17, 13 already displayed an elevated rate of synthesis in M17 at neutral pH. These proteins could play an important role in the development of the protein de novo synthesis-independent ATR observed in M17.
Published: 2005
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46. Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic Acid microarrays identifies several candidate genes as markers of malignancy

Author: Eric Baudin, Jérôme Bertherat, Olivier Chabre, Pierre-François Plouin, Xavier Bertagna, Rémi Houlgatte, Christine Gicquel, Gwennaelle Le Moigne, François Berger, Nadia Cherradi, Florence de Fraipont, G. Defaye, Jean-Jacques Feige, Michelle El Atifi, Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Angiogenèse hormono-régulée et angiogenèse tumorale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine vasculaire et hypertension artérielle [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Endocrinologie et Diabétologie, INSERM Ligue Nationale contre le Cancer (CIT-1) GEFLUC Dauphiné-Savoie PHRC (AOM95201), Service d'explorations fonctionnelles [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Feige, Jean-Jacques, 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 ), Technologies avancées pour le génôme et la clinique ( TAGC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Service d'explorations fonctionnelles, and CHU Trousseau [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Male, Candidate gene, MESH : RNA, Messenger, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, MESH : Aged, MESH : Adrenal Cortex Neoplasms, MESH: Adrenal Cortex Neoplasms, MESH: Genetic Markers, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Endocrinology, MESH : Tumor Markers, Biological, MESH : Genetic Markers, Adrenocortical carcinoma, MESH : Female, Oligonucleotide Array Sequence Analysis, MESH: Aged, education.field_of_study, MESH: Middle Aged, MESH: Gene Expression Regulation, Neoplastic, MESH : Adult, Middle Aged, 3. Good health, Gene Expression Regulation, Neoplastic, MESH : Oligonucleotide Array Sequence Analysis, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, Female, Steroids, DNA microarray, Adult, Genetic Markers, medicine.medical_specialty, Adolescent, MESH : Gene Expression Regulation, Neoplastic, MESH : Male, Population, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Disease-Free Survival, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Adolescent, Internal medicine, Biomarkers, Tumor, medicine, Humans, MESH : Middle Aged, RNA, Messenger, education, Gene, Aged, MESH: RNA, Messenger, MESH: Adolescent, MESH: Humans, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, Biochemistry (medical), Cancer, MESH: Adult, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, MESH: Steroids, Gene expression profiling, MESH: Oligonucleotide Array Sequence Analysis, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, Candidate Disease Gene, MESH: Female, MESH : Steroids
Abstract: International audience; The aim of this study was to identify predictor sets of genes whose over- or underexpression in human sporadic adrenocortical tumors would help to identify malignant vs. benign tumors and to predict postsurgical metastatic recurrence. For this, we analyzed the expression of 230 candidate genes using cDNA microarrays in a series of 57 well-characterized human sporadic adrenocortical tumors (33 adenomas and 24 carcinomas). We identified two clusters of genes (the IGF-II cluster containing eight genes, including IGF-II, and the steroidogenesis cluster containing six genes encoding steroidogenic enzymes plus eight other genes) whose combined levels of expression appeared to be good predictors of malignancy. This predictive value was as strong as that of the pathological score of Weiss. The analysis of the population of carcinomas (13 tumors) for genes whose expression would be strongly different between recurring and nonrecurring tumors allowed identification of 14 genes meeting these criteria. Among these genes, there are probably new markers of tumor evolution that will deserve additional validation on a larger scale. Taken together, these results show that the parallel analysis of the expression levels of a selected group of genes on microgram quantities of tumor RNA (a quantity that can be obtained from fine needle aspirations) appears as a complementary method to histopathology for the diagnosis and prognosis of evolution of adrenocortical carcinomas.
Published: 2005
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47. CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence

Author: Marie-Cécile, Lamy, Mohammed, Zouine, Juliette, Fert, Massimo, Vergassola, Elisabeth, Couve, Elisabeth, Pellegrini, Philippe, Glaser, Frank, Kunst, Tarek, Msadek, Patrick, Trieu-Cuot, Claire, Poyart, Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Bactériologie, CHU Cochin [AP-HP], Génomique des Microorganismes Pathogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by research funds from the Institut National de la Santé et de la Recherche Médicale, the European Commission (Grant QLG2‐CT‐1999‐01455), the Centre National de la Recherche Scientifique, the Institut Pasteur (PTR No. 17 and GPH No. 9), and the Universities Paris 5 and Paris 7. M.‐C. Lamy was supported by the Ministère de la Recherche et des Technologies and the Fondation pour la Recherche Médicale., We are grateful to J.L. Berretti for determination of haemolytic activities, D. Euphrasie for help in the construction of the ΔCylE mutant, and S. Dubrac and C. Buchrieser for helpful discussion., and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH : Virulence Factors, MESH : Hemolysis, Transcription, Genetic, MESH : Operon, MESH : Streptococcal Infections, MESH : Gene Deletion, MESH: Virulence, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial Adhesion, Hemolysin Proteins, MESH: Streptococcal Infections, MESH : Bacterial Proteins, MESH: Animals, Promoter Regions, Genetic, MESH: Bacterial Proteins, MESH: Gene Expression Regulation, Bacterial, Virulence, MESH : Rats, MESH : Genes, Bacterial, MESH : Virulence, MESH : Streptococcus agalactiae, MESH: Hemolysis, MESH : Epithelial Cells, MESH: Promoter Regions (Genetics), MESH: Hemolysin Proteins, MESH: Repressor Proteins, MESH: Epithelial Cells, MESH: Regulon, MESH: Genes, Bacterial, MESH : Repressor Proteins, Signal Transduction, MESH : Gene Expression Regulation, Bacterial, MESH: Operon, MESH: Rats, Virulence Factors, MESH : Bacterial Adhesion, MESH : Regulon, MESH : Hemolysin Proteins, MESH : Protein Kinases, Hemolysis, Regulon, Streptococcus agalactiae, Lethal Dose 50, MESH: Gene Expression Profiling, Bacterial Proteins, Streptococcal Infections, Operon, Animals, Humans, MESH : Lethal Dose 50, MESH: Bacterial Adhesion, MESH: Protein Kinases, MESH: Virulence Factors, MESH : Signal Transduction, MESH: Humans, Gene Expression Profiling, MESH: Transcription, Genetic, MESH : Gene Expression Profiling, MESH : Humans, MESH : Transcription, Genetic, Epithelial Cells, Gene Expression Regulation, Bacterial, MESH: Streptococcus agalactiae, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Promoter Regions (Genetics), MESH : Disease Models, Animal, Rats, Repressor Proteins, Disease Models, Animal, MESH: Lethal Dose 50, Genes, Bacterial, MESH: Gene Deletion, MESH : Animals, MESH: Disease Models, Animal, Protein Kinases, Gene Deletion
Abstract: International audience; In this study, we carried out a detailed structural and functional analysis of a Streptococcus agalactiae (GBS) two-component system which is orthologous to the CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes. In GBS, covR and covS are part of a seven gene operon transcribed from two promoters that are not regulated by CovR. A DeltacovSR mutant was found to display dramatic phenotypic changes such as increased haemolytic activity and reduced CAMP activity on blood agar. Adherence of the DeltacovSR mutant to epithelial cells was greatly increased and analysis by transmission electron microscopy revealed the presence at its surface of a fibrous extracellular matrix that might be involved in these intercellular interactions. However, the DeltacovSR mutant was unable to initiate growth in RPMI and its viability in human normal serum was greatly impaired. A major finding of this phenotypic analysis was that the CovS/CovR system is important for GBS virulence, as a 3 log increase of the LD(50) of the mutant strain was observed in the neonate rat sepsis model. The pleiotropic phenotype of the DeltacovSR mutant is in full agreement with the large number of genes controlled by CovS/CovR as seen by expression profiling analysis, many of which encode potentially secreted or cell surface-associated proteins: 76 genes are repressed whereas 63 were positively regulated. CovR was shown to bind directly to the regulatory regions of several of these genes and a consensus CovR recognition sequence was proposed using both DNase I footprinting and computational analyses.
Published: 2004
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48. Human blood IgM 'memory' B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire

Author: C.A. Reynaud, Mary Ellen Conley, Louis M. Staudt, Olivier Tournilhac, J.C. Weill, Jean-Laurent Casanova, Damien Bonnet, Andreas Rosenwald, Sandra K. Weller, Corinne Cordier, Bruce K. Tan, Gil Tchernia, Birte Steiniger, Alessandro Plebani, Moritz C. Braun, D S Kumararatne, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Metabolism Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-Center for Cancer Research-National Institutes of Health, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Immunology, St Jude Children's Research Hospital-The University of Tennessee Health Science Center [Memphis] (UTHSC), Università degli Studi di Brescia [Brescia], Departments of Clinical Immunology and Medicine, Addenbrooke's Hospital, Service de cardiologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institute of Anatomy and Cell Biology, University of Marburg, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), National Cancer Institute ( NIH ) -Center for Cancer Research-National Institutes of Health, IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), St Jude Children's Research Hospital-University of Tennessee College of Medicine, Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Weller, Sandra, Università degli Studi di Brescia = University of Brescia (UniBs), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH: Spleen, MESH: Antigens, CD27, MESH : Aged, MESH : Child, Preschool, Biochemistry, Immunoglobulin D, 0302 clinical medicine, MESH : Child, immune system diseases, MESH: Autoimmune Diseases, MESH: Child, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Child, Gene Rearrangement, B-Lymphocyte, MESH: Aged, 0303 health sciences, B-Lymphocytes, MESH: Middle Aged, biology, MESH: Gene Rearrangement, B-Lymphocyte, MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Hematology, Middle Aged, MESH : Adult, Marginal zone, MESH: Infant, MESH: Immunoglobulin M, medicine.anatomical_structure, Child, Preschool, MESH : Immunophenotyping, Blood Circulation, MESH: Immunologic Memory, MESH: Complementarity Determining Regions, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Blood Circulation, Antibody, Adult, MESH : Spleen, MESH: Somatic Hypermutation, Immunoglobulin, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH: Immunophenotyping, MESH : Immunologic Memory, MESH : Immunoglobulin M, Immunology, MESH : Somatic Hypermutation, Immunoglobulin, Somatic hypermutation, MESH : Complementarity Determining Regions, Spleen, chemical and pharmacologic phenomena, Article, MESH : Immunoglobulin D, Autoimmune Diseases, Immunophenotyping, MESH : B-Lymphocytes, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Autoimmune Diseases, MESH : Antigens, CD27, MESH : Adolescent, MESH: B-Lymphocytes, medicine, Humans, MESH : Middle Aged, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, MESH: Child, Preschool, Infant, MESH: Blood Circulation, MESH: Adult, Cell Biology, Gene rearrangement, Complementarity Determining Regions, Tumor Necrosis Factor Receptor Superfamily, Member 7, B-1 cell, Immunoglobulin M, MESH : Gene Rearrangement, B-Lymphocyte, biology.protein, Somatic Hypermutation, Immunoglobulin, Immunologic Memory, 030215 immunology
Abstract: International audience; The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-independent response, and gene-expression profiling of the different blood and splenic B-cell subsets, we show here that blood IgM(+)IgD(+)CD27(+) cells correspond to circulating splenic marginal zone B cells. Furthermore, analysis of this peripheral subset in healthy children younger than 2 years shows that these B cells develop and mutate their immunoglobulin receptor during ontogeny, prior to their differentiation into T-independent antigen-responsive cells. It is therefore proposed that these IgM(+)IgD(+)CD27(+) B cells provide the splenic marginal zone with a diversified and protective preimmune repertoire in charge of the responses against encapsulated bacteria.
Published: 2004
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49. Assessment of 35mer amino-modified oligonucleotide based microarray with bacterial samples

Author: Jean-Pierre Cloarec, Federica Calevro, Vincent Dugas, Jacques Bernillon, Gérard Febvay, Hubert Charles, J.M. Fayard, Nancie Reymond, Yvan Rahbé, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), 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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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), Biologie Fonctionnelle, Insectes et Interactions ( BF2I ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS )
Subjects: MESH: Buchnera, Microarray, MESH : DNA, Complementary, Base Pair Mismatch, MESH: Oligonucleotide Probes, MESH: Nucleic Acid Hybridization, Complementary, [ SDV.EE.IEO ] Life Sciences [q-bio]/Ecology, environment/Symbiosis, MESH : Buchnera, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, biology, DNA-encoded chemical library, Bacterial, Nucleic Acid Hybridization, MESH : Nucleic Acid Hybridization, MESH : Oligonucleotide Array Sequence Analysis, RNA, Bacterial, DNA microarray, MESH : Sensitivity and Specificity, MESH: RNA, Bacterial, Microbiology (medical), MESH : Fluorescence, DNA, Complementary, Computational biology, Microbiology, Sensitivity and Specificity, Fluorescence, Database normalization, 03 medical and health sciences, MESH: Gene Expression Profiling, Buchnera, Molecular Biology, 030304 developmental biology, MESH : Base Pair Mismatch, MESH: Base Pair Mismatch, 030306 microbiology, Oligonucleotide, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH: Fluorescence, DNA, MESH: DNA, Complementary, MESH : RNA, Bacterial, biology.organism_classification, MESH: Sensitivity and Specificity, MESH : Oligonucleotide Probes, Gene expression profiling, MESH: Oligonucleotide Array Sequence Analysis, Gene chip analysis, RNA, Oligonucleotide Probes, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Parallel quantification of a large number of messenger RNA transcripts, using microarray technology, promises to provide unsuspected information about many cellular processes. Although experimental protocols on microarray applications are available, only limited methodological information on glass-slide manufacturing and signal interpretation has been published. The aim of this paper is to provide new insights into the practical aspects of the construction and hybridization of oligonucleotide-based microarrays. The intracellular symbiotic bacterium of aphids, Buchnera aphidicola, is used here as a model organism. The first part of the work is devoted to the optimization of procedures for printing slides, labeling of cDNA targets and hybridization. In the second part, based on a statistical analysis of the results, we discuss the influence of the probe attachment chemistry, of the labeling method, of the oligonucleotide position and of the concentration of a spotted oligonucleotide on signal intensity. The problem of signal specificity is also addressed, based on the calculation of the fluorescent ratio for each probe to its corresponding mismatch control probe. Lastly, the selection of internal spiked RNAs appropriate to our bacterial samples and useful for the data normalization step is presented.
Published: 2004
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50. Analysis of prolactin-modulated gene expression profiles during the Nb2 cell cycle using differential screening techniques

Author: Bole-Feysot, Christine, Perret, Eric, Roustan, Paul, Bouchard, Brigitte, Kelly, Paul, Autard, Delphine, Endocrinologie moléculaire, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Biologie Moléculaire du Gène, and Sanofi Aventis Recherche
Subjects: MESH : Cell Survival, MESH : RNA, Messenger, MESH : Cloning, Molecular, MESH : Rats, MESH : Flow Cytometry, MESH : Gene Expression Regulation, Neoplastic, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Gene Expression Profiling, MESH : Eukaryotic Cells, MESH : Cell Division, MESH : Reprodu, MESH : Neoplasm Proteins, MESH : RNA, Neoplasm, MESH : Prolactin, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Mammals, MESH : Cell Cycle, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Animals, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: BACKGROUND: Rat Nb2-11C lymphoma cells are dependent on prolactin for proliferation and are widely used to study prolactin signaling pathways. To investigate the role of this hormone in the transcriptional mechanisms that underlie prolactin-stimulated mitogenesis, five different techniques were used to isolate differentially expressed transcripts: mRNA differential display, representational difference analysis (RDA), subtractive suppressive hybridization (SSH), analysis of weakly expressed candidate genes, and differential screening of an organized library. RESULTS: About 70 transcripts were found to be modulated in Nb2 cells following prolactin treatment. Of these, approximately 20 represent unknown genes. All cDNAs were characterized by northern blot analysis and categorized on the basis of their expression profiles and the functions of the known genes. We compared our data with other cell-cycle-regulated transcripts and found several new potential signaling molecules that may be involved in Nb2 cell growth. In addition, abnormalities in the expression patterns of several transcripts were detected in Nb2 cells, including the constitutive expression of the immediate-early gene EGR-1. Finally, we compared the differential screening techniques in terms of sensitivity, efficiency and occurrence of false positives. CONCLUSIONS: Using these techniques to determine which genes are differentially expressed in Nb2 lymphoma cells, we have obtained valuable insight into the potential functions of some of these genes in the cell cycle. Although this information is preliminary, comparison with other eukaryotic models of cell-cycle progression enables identification of expression abnormalities and proteins potentially involved in signal transduction, which could indicate new directions for research.
Published: 2000

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