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1. Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection

Author: Nam Nguyen Quang, Sophie Goudey, Emmanuel Ségéral, Ammara Mohammad, Sophie Lemoine, Corinne Blugeon, Margaux Versapuech, Jean-Christophe Paillart, Clarisse Berlioz-Torrent, Stéphane Emiliani, and Sarah Gallois-Montbrun
Subjects: HIV RNA, Alternative splicing, Viral transcriptome, ONT long-read sequencing, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background Alternative splicing is a key step in Human Immunodeficiency Virus type 1 (HIV-1) replication that is tightly regulated both temporally and spatially. More than 50 different transcripts can be generated from a single HIV-1 unspliced pre-messenger RNA (pre-mRNA) and a balanced proportion of unspliced and spliced transcripts is critical for the production of infectious virions. Understanding the mechanisms involved in the regulation of viral RNA is therefore of potential therapeutic interest. However, monitoring the regulation of alternative splicing events at a transcriptome-wide level during cell infection is challenging. Here we used the long-read cDNA sequencing developed by Oxford Nanopore Technologies (ONT) to explore in a quantitative manner the complexity of the HIV-1 transcriptome regulation in infected primary CD4+ T cells. Results ONT reads mapping to the viral genome proved sufficiently long to span all possible splice junctions, even distant ones, and to be assigned to a total of 150 exon combinations. Fifty-three viral RNA isoforms, including 14 new ones were further considered for quantification. Relative levels of viral RNAs determined by ONT sequencing showed a high degree of reproducibility, compared favourably to those produced in previous reports and highly correlated with quantitative PCR (qPCR) data. To get further insights into alternative splicing regulation, we then compiled quantifications of splice site (SS) usage and transcript levels to build “splice trees”, a quantitative representation of the cascade of events leading to the different viral isoforms. This approach allowed visualizing the complete rewiring of SS usages upon perturbation of SS D2 and its impact on viral isoform levels. Furthermore, we produced the first dynamic picture of the cascade of events occurring between 12 and 24 h of viral infection. In particular, our data highlighted the importance of non-coding exons in viral RNA transcriptome regulation. Conclusion ONT sequencing is a convenient and reliable strategy that enabled us to grasp the dynamic of the early splicing events modulating the viral RNA landscape in HIV-1 infected cells.
Published: 2020
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2. Arabidopsis S2Lb links AtCOMPASS-like and SDG2 activity in H3K4me3 independently from histone H2B monoubiquitination

Author: Anne-Sophie Fiorucci, Clara Bourbousse, Lorenzo Concia, Martin Rougée, Anne-Flore Deton-Cabanillas, Gérald Zabulon, Elodie Layat, David Latrasse, Soon Kap Kim, Nicole Chaumont, Bérangère Lombard, David Stroebel, Sophie Lemoine, Ammara Mohammad, Corinne Blugeon, Damarys Loew, Christophe Bailly, Chris Bowler, Moussa Benhamed, and Fredy Barneche
Subjects: Biology (General), QH301-705.5, Genetics, QH426-470
Abstract: Abstract Background The functional determinants of H3K4me3, their potential dependency on histone H2B monoubiquitination, and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike in Saccharomyces cerevisiae, where a single SET1 protein catalyzes H3K4me3 as part of COMPlex of proteins ASsociated with Set1 (COMPASS), in Arabidopsis thaliana, this activity involves multiple histone methyltransferases. Among these, the plant-specific SET DOMAIN GROUP 2 (SDG2) has a prominent role. Results We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. We show that S2Lb co-purifies with the AtCOMPASS core subunit WDR5, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes. S2Lb knockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. However, s2lb seedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2, or H3K4me3, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Conclusions Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been co-opted by the plant-specific SDG2 histone methyltransferase and mediates H3K4me3 deposition through an H2B monoubiquitination-independent pathway in Arabidopsis.
Published: 2019
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3. Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1

Author: Serena Barilla, Ning Liang, Enrichetta Mileti, Raphaëlle Ballaire, Marie Lhomme, Maharajah Ponnaiah, Sophie Lemoine, Antoine Soprani, Jean-Francois Gautier, Ez-Zoubir Amri, Wilfried Le Goff, Nicolas Venteclef, and Eckardt Treuter
Subjects: Adipocytes, Adipogenesis, Hypertrophy, Obesity, Type 2 diabetes, GPS2, Internal medicine, RC31-1245
Abstract: Objective: Adipogenesis is critical for adipose tissue remodeling during the development of obesity. While the role of transcription factors in the orchestration of adipogenic pathways is already established, the involvement of coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses remains poorly understood. The aim of our study was to investigate which pathways are controlled by G protein pathway suppressor 2 (GPS2) during the differentiation of human adipocytes. Methods: We generated a unique loss-of-function model by RNAi depletion of GPS2 in human multipotent adipose-derived stem (hMADS) cells. We thoroughly characterized the coregulator depletion-dependent pathway alterations during adipocyte differentiation at the level of transcriptome (RNA-seq), epigenome (ChIP-seq H3K27ac), cistrome (ChIP-seq GPS2), and lipidome. We validated the in vivo relevance of the identified pathways in non-diabetic and diabetic obese patients. Results: The loss of GPS2 triggers the reprogramming of cellular processes related to adipocyte differentiation by increasing the responses to the adipogenic cocktail. In particular, GPS2 depletion increases the expression of BMP4, an important trigger for the commitment of fibroblast-like progenitors toward the adipogenic lineage and increases the expression of inflammatory and metabolic genes. GPS2-depleted human adipocytes are characterized by hypertrophy, triglyceride and phospholipid accumulation, and sphingomyelin depletion. These changes are likely a consequence of the increased expression of ATP-binding cassette subfamily G member 1 (ABCG1) that mediates sphingomyelin efflux from adipocytes and modulates lipoprotein lipase (LPL) activity. We identify ABCG1 as a direct transcriptional target, as GPS2 depletion leads to coordinated changes of transcription and H3K27 acetylation at promoters and enhancers that are occupied by GPS2 in wild-type adipocytes. We find that in omental adipose tissue of obese humans, GPS2 levels correlate with ABCG1 levels, type 2 diabetic status, and lipid metabolic status, supporting the in vivo relevance of the hMADS cell-derived in vitro data. Conclusion: Our study reveals a dual regulatory role of GPS2 in epigenetically modulating the chromatin landscape and gene expression during human adipocyte differentiation and identifies a hitherto unknown GPS2-ABCG1 pathway potentially linked to adipocyte hypertrophy in humans.
Published: 2020
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4. Active intermixing of indirect and direct neurons builds the striatal mosaic

Author: Andrea Tinterri, Fabien Menardy, Marco A. Diana, Ludmilla Lokmane, Maryama Keita, Fanny Coulpier, Sophie Lemoine, Caroline Mailhes, Benjamin Mathieu, Paloma Merchan-Sala, Kenneth Campbell, Ildiko Gyory, Rudolf Grosschedl, Daniela Popa, and Sonia Garel
Subjects: Science
Abstract: Striatal projection neurons exist as two distinct classes and are anatomically mixed in the brain. Here, Tinterri and colleagues show the developmental mechanism of this cellular mosaicism that relies on an intrinsic transcription factor for cell type specification and intermixed cellular migration.
Published: 2018
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5. Genome sequencing and transcriptome analysis of Trichoderma reesei QM9978 strain reveals a distal chromosome translocation to be responsible for loss of vib1 expression and loss of cellulase induction

Author: Christa Ivanova, Jonas Ramoni, Thiziri Aouam, Alexa Frischmann, Bernhard Seiboth, Scott E. Baker, Stéphane Le Crom, Sophie Lemoine, Antoine Margeot, and Frédérique Bidard
Subjects: Trichoderma reesei, Genome analysis, Transcriptome, vib1, Cellulase production, Promoter, Fuel, TP315-360, Biotechnology, TP248.13-248.65
Abstract: Abstract Background The hydrolysis of biomass to simple sugars used for the production of biofuels in biorefineries requires the action of cellulolytic enzyme mixtures. During the last 50 years, the ascomycete Trichoderma reesei, the main source of industrial cellulase and hemicellulase cocktails, has been subjected to several rounds of classical mutagenesis with the aim to obtain higher production levels. During these random genetic events, strains unable to produce cellulases were generated. Here, whole genome sequencing and transcriptomic analyses of the cellulase-negative strain QM9978 were used for the identification of mutations underlying this cellulase-negative phenotype. Results Sequence comparison of the cellulase-negative strain QM9978 to the reference strain QM6a identified a total of 43 mutations, of which 33 were located either close to or in coding regions. From those, we identified 23 single-nucleotide variants, nine InDels, and one translocation. The translocation occurred between chromosomes V and VII, is located upstream of the putative transcription factor vib1, and abolishes its expression in QM9978 as detected during the transcriptomic analyses. Ectopic expression of vib1 under the control of its native promoter as well as overexpression of vib1 under the control of a strong constitutive promoter restored cellulase expression in QM9978, thus confirming that the translocation event is the reason for the cellulase-negative phenotype. Gene deletion of vib1 in the moderate producer strain QM9414 and in the high producer strain Rut-C30 reduced cellulase expression in both cases. Overexpression of vib1 in QM9414 and Rut-C30 had no effect on cellulase production, most likely because vib1 is already expressed at an optimal level under normal conditions. Conclusion We were able to establish a link between a chromosomal translocation in QM9978 and the cellulase-negative phenotype of the strain. We identified the transcription factor vib1 as a key regulator of cellulases in T. reesei whose expression is absent in QM9978. We propose that in T. reesei, as in Neurospora crassa, vib1 is involved in cellulase induction, although the exact mechanism remains to be elucidated. The data presented here show an example of a combined genome sequencing and transcriptomic approach to explain a specific trait, in this case the QM9978 cellulase-negative phenotype, and how it helps to better understand the mechanisms during cellulase gene regulation. When focusing on mutations on the single base-pair level, changes on the chromosome level can be easily overlooked and through this work we provide an example that stresses the importance of the big picture of the genomic landscape during analysis of sequencing data.
Published: 2017
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6. High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

Author: John Mouaikel, Sébastien Z. Causse, Mathieu Rougemaille, Yves Daubenton-Carafa, Corinne Blugeon, Sophie Lemoine, Frédéric Devaux, Xavier Darzacq, and Domenico Libri
Subjects: Biology (General), QH301-705.5
Abstract: The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single-molecule fluorescence in situ hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase occupancy genome wide. We propose that the THO complex is required for tuning the dynamic of gene-nuclear pore association and mRNP release to the same high pace of transcription initiation.
Published: 2013
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7. Effects of Acute Supramaximal Cycle Exercise on Plasma FFA Concentration in Obese Adolescent Boys.

Author: Georges Jabbour, Horia-Daniel Iancu, Anne Paulin, Jean-Marc Lavoie, Sophie Lemoine-Morel, and Hassane Zouhal
Subjects: Medicine, Science
Abstract: The aims of the present study are 1) to evaluate the free fatty acid (FFA) profile and 2) to determine the relative anaerobic and aerobic contributions to total energy consumption during repeated supramaximal cycling bouts (SCE) in adolescent boys with different body weight statuses.Normal-weight (NW), overweight (OW), and obese (OB) adolescent boys (n =15 per group) completed a SCE sessions consisted of 6 x 6s maximal sprints with 2 min of passive rest between each repetition. Plasma FFA levels were determined at rest, immediately after a 10 min warm-up, and immediately at the end of SCE. The anaerobic and aerobic contributions (%) were measured via repeated SCE bouts. Insulin resistance was calculated using the homoeostatic model assessment (HOMA-IR) index.The FFA concentrations measured immediately after SCE were higher in the OB group than in the OW and NW (p
Published: 2015
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8. Role of the DHH1 gene in the regulation of monocarboxylic acids transporters expression in Saccharomyces cerevisiae.

Author: Sandra Mota, Neide Vieira, Sónia Barbosa, Thierry Delaveau, Claire Torchet, Agnès Le Saux, Mathilde Garcia, Ana Pereira, Sophie Lemoine, Fanny Coulpier, Xavier Darzacq, Lionel Benard, Margarida Casal, Frédéric Devaux, and Sandra Paiva
Subjects: Medicine, Science
Abstract: Previous experiments revealed that DHH1, a RNA helicase involved in the regulation of mRNA stability and translation, complemented the phenotype of a Saccharomyces cerevisiae mutant affected in the expression of genes coding for monocarboxylic-acids transporters, JEN1 and ADY2 (Paiva S, Althoff S, Casal M, Leao C. FEMS Microbiol Lett, 1999, 170:301-306). In wild type cells, JEN1 expression had been shown to be undetectable in the presence of glucose or formic acid, and induced in the presence of lactate. In this work, we show that JEN1 mRNA accumulates in a dhh1 mutant, when formic acid was used as sole carbon source. Dhh1 interacts with the decapping activator Dcp1 and with the deadenylase complex. This led to the hypothesis that JEN1 expression is post-transcriptionally regulated by Dhh1 in formic acid. Analyses of JEN1 mRNAs decay in wild-type and dhh1 mutant strains confirmed this hypothesis. In these conditions, the stabilized JEN1 mRNA was associated to polysomes but no Jen1 protein could be detected, either by measurable lactate carrier activity, Jen1-GFP fluorescence detection or western blots. These results revealed the complexity of the expression regulation of JEN1 in S. cerevisiae and evidenced the importance of DHH1 in this process. Additionally, microarray analyses of dhh1 mutant indicated that Dhh1 plays a large role in metabolic adaptation, suggesting that carbon source changes triggers a complex interplay between transcriptional and post-transcriptional effects.
Published: 2014
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9. Yeast mitochondrial biogenesis: a role for the PUF RNA-binding protein Puf3p in mRNA localization.

Author: Yann Saint-Georges, Mathilde Garcia, Thierry Delaveau, Laurent Jourdren, Stephane Le Crom, Sophie Lemoine, Veronique Tanty, Frederic Devaux, and Claude Jacq
Subjects: Medicine, Science
Abstract: The asymmetric localization of mRNA plays an important role in coordinating posttranscriptional events in eukaryotic cells. We investigated the peripheral mitochondrial localization of nuclear-encoded mRNAs (MLR) in various conditions in which the mRNA binding protein context and the translation efficiency were altered. We identified Puf3p, a Pumilio family RNA-binding protein, as the first trans-acting factor controlling the MLR phenomenon. This allowed the characterization of two classes of genes whose mRNAs are translated to the vicinity of mitochondria. Class I mRNAs (256 genes) have a Puf3p binding motif in their 3'UTR region and many of them have their MLR properties deeply affected by PUF3 deletion. Conversely, mutations in the Puf3p binding motif alter the mitochondrial localization of BCS1 mRNA. Class II mRNAs (224 genes) have no Puf3p binding site and their asymmetric localization is not affected by the absence of PUF3. In agreement with a co-translational import process, we observed that the presence of puromycin loosens the interactions between most of the MLR-mRNAs and mitochondria. Unexpectedly, cycloheximide, supposed to solidify translational complexes, turned out to destabilize a class of mRNA-mitochondria interactions. Classes I and II mRNAs, which are therefore transported to the mitochondria through different pathways, correlated with different functional modules. Indeed, Class I genes code principally for the assembly factors of respiratory chain complexes and the mitochondrial translation machinery (ribosomes and translation regulators). Class II genes encode proteins of the respiratory chain or proteins involved in metabolic pathways. Thus, MLR, which is intimately linked to translation control, and the activity of mRNA-binding proteins like Puf3p, may provide the conditions for a fine spatiotemporal control of mitochondrial protein import and mitochondrial protein complex assembly. This work therefore provides new openings for the global study of mitochondria biogenesis.
Published: 2008
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10. Table S1 from Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells

Author: Piotr Topilko, Patrick Charnay, Jean-Michel Vallat, Pierre Wolkenstein, Sophie Lemoine, Amal Debbiche, Alain Schmitt, Aurelie Gresset, Fanny Coulpier, and Katarzyna J. Radomska
Abstract: Tumour phenotypes in Prss56Cre, R26tdTom, Nf1flox/flox and Prss56Cre, R26tdTom, Nf1flox/- mice
Published: 2023

11. Supplementary Materials and Methods from Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells

Author: Piotr Topilko, Patrick Charnay, Jean-Michel Vallat, Pierre Wolkenstein, Sophie Lemoine, Amal Debbiche, Alain Schmitt, Aurelie Gresset, Fanny Coulpier, and Katarzyna J. Radomska
Abstract: Supplementary Materials and Methods
Published: 2023

12. Supplementary Figures S1-S6 from Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells

Author: Piotr Topilko, Patrick Charnay, Jean-Michel Vallat, Pierre Wolkenstein, Sophie Lemoine, Amal Debbiche, Alain Schmitt, Aurelie Gresset, Fanny Coulpier, and Katarzyna J. Radomska
Abstract: Supplementary Figures S1-S6
Published: 2023

13. Supplementary Figure Legends from Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells

Author: Piotr Topilko, Patrick Charnay, Jean-Michel Vallat, Pierre Wolkenstein, Sophie Lemoine, Amal Debbiche, Alain Schmitt, Aurelie Gresset, Fanny Coulpier, and Katarzyna J. Radomska
Abstract: Supplementary Figure Legends
Published: 2023

14. The Tumor Microenvironment Impairs Th1 IFNγ Secretion through Alternative Splicing Modifications of Irf1 Pre-mRNA

Author: Sophie Lemoine, Christophe Hibos, Joséphine Melin, Frédérique Végran, Antoine Bernard, Sandy Chevrier, Romain Mary, Romain Boidot, Etienne Viltard, Paul Peixoto, Etienne Humblin, Fanny Chalmin, François Ghiringhelli, Mélanie Bruchard, Lionel Apetoh, Corentin Richard, Eric Hervouet, Théo Accogli, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université de Bourgogne (UB), GenomiqueENS (Genomique ENS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Thomas-Chollier, Morgane
Subjects: 0301 basic medicine, Gene isoform, Cancer Research, Tumor microenvironment, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Chemistry, Immunology, Alternative splicing, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, 03 medical and health sciences, Splicing factor, 030104 developmental biology, 0302 clinical medicine, Immune system, IRF1, 030220 oncology & carcinogenesis, Precursor mRNA, Transcription factor
Abstract: It is clearly established that the immune system can affect cancer response to therapy. However, the influence of the tumor microenvironment (TME) on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect the immune system. Here, we showed that the TME, via a TGFβ-dependent mechanism, increased alternative splicing events and induced the expression of an alternative isoform of the IRF1 transcription factor (IRF1Δ7) in Th1 cells. We found that the SFPQ splicing factor (splicing factor, proline- and glutamine-rich) was responsible for the IRF1Δ7 production. We also showed, in both mice and humans, that the IRF1 alternative isoform altered the full-length IRF1 transcriptional activity on the Il12rb1 promoter, resulting in decreased IFNγ secretion in Th1 cells. Thus, the IRF1Δ7 isoform was increased in the TME, and inhibiting IRF1Δ7 expression could potentiate Th1 antitumor responses.
Published: 2021

15. A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity

Author: Klein L, Van Steenwinckel J, Corinne Blugeon, Thomas Schmitz, Dulcie A. Vousden, Sophie Lemoine, buehrer C, Pierre Gressens, Cindy Bokobza, Leslie Schwendimann, Zsolt Csaba, J. P. Lerch, Anthony C. Vernon, Bobbi Fleiss, Faivre, and Till Scheuer
Subjects: medicine.medical_specialty, Cerebellum, medicine.medical_treatment, Interleukin-1beta, Encephalopathy, Inflammation, Infant, Premature, Diseases, Systemic inflammation, White matter, Cellular and Molecular Neuroscience, Myelin, Cerebellar Diseases, Pregnancy, Internal medicine, Animals, Humans, Medicine, Brain Diseases, Microglia, business.industry, Infant, Newborn, medicine.disease, Disease Models, Animal, Cytokine, medicine.anatomical_structure, Endocrinology, Neurology, nervous system, Interferon Type I, Female, medicine.symptom, business, Infant, Premature
Abstract: Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Because 1 in 10 babies is born preterm cerebellar injury is a significant clinical problem. The causes of cerebellar damage are yet to be fully explained. Herein, we tested the hypothesis that perinatal inflammatory stimuli may play a key role in cerebellar injury of preterm infants. We undertook our studies in an established mouse model of inflammation-induced encephalopathy of prematurity driven by systemic administration of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β). Inflammation is induced between postnatal day (P) 1 to day 5, timing equivalent to the last trimester for brain development in humans the period of vulnerability to preterm birth related brain injury. We investigated acute and long-term consequences for the cerebellum on brain volume expansion, oligodendroglial maturation, myelin levels and the microglial transcriptome. Perinatal inflammation induced global mouse brain volume reductions, including specific grey and white matter volume reductions in cerebellar lobules I and II (5% FDR) in IL-1β versus control treated mice from P15 onwards. Oligodendroglia damage preceded the MRI-detectable volume changes, as evidenced by a reduced proliferation of OLIG2+ cells at P10 and reduced levels of the myelin proteins MOG, MBP and MAG at P10 and P15. Increased density of Iba1+ cerebellar microglia was observed at P5 and P45, with evidence for increased microglial proliferation at P5 and P10. Comparison of the transcriptome of microglia isolated from P5 cerebelli and cerebrum revealed significant enrichment of pro-inflammatory markers in microglia from both regions, but in the cerebellum microglia displayed a unique type I interferon signalling dysregulation. Collectively, these data suggest that in our model that systemic inflammation causes chronic activation of microglia and maldevelopment of cerebellum that includes myelin deficits which is driven in the cerebellum by type I interferon signalling. Future protective strategies for preterm infants should consider sustained type I interferon signalling driven cerebellar inflammation as an important target.
Published: 2021

16. Zinc Uptake and Storage During the Formation of the Cerebral Cortex in Mice

Author: Sophie Lemoine, Alexandre Bouron, Jessy Hasna, Corinne Blugeon, Sylvain Bohic, Biologie des Métaux (BioMet), 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])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), European Synchrotron Radiation Facility (ESRF), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), GenomiqueENS (Genomique ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, and ANR-16-CE29-0024,ImaZinc,Homéostasie du zinc lors de la corticogénese(2016)
Subjects: 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuroscience (miscellaneous), Embryonic Development, Transcriptome, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cortex (anatomy), medicine, Animals, Cerebral Cortex, Neurons, Neocortex, Chemistry, Embryogenesis, Membrane Transport Proteins, Reproducibility of Results, Embryonic stem cell, Cell biology, Mice, Inbred C57BL, Zinc, Corticogenesis, 030104 developmental biology, medicine.anatomical_structure, Neurology, Cerebral cortex, 030217 neurology & neurosurgery, Homeostasis, Transcription Factors
Abstract: International audience; The cerebral cortex (or neocortex) is a brain structure formed during embryogenesis. The present study seeks to provide a detailed characterization of the Zn homeostatic mechanisms during cerebral cortex formation and development. To reach that goal, we have combined high-throughput RNA-sequencing analysis of the whole murine genome, X-ray fluorescence nanoimaging (XRF), inductively coupled plasma-atomic emission spectrometry (ICP-AES), and live-cell imaging of dissociated cortical neurons loaded with the Zn fluorescent probe FluoZin-3. The transcriptomic analysis was conducted from mRNAs isolated from cortices collected at embryonic (E) days 11 (E11), E13, and E17 and on postnatal day 1 (PN1) pups. This permitted to characterize the temporal pattern of expression of the main genes participating in the cellular transport, storage, and release of Zn during corticogenesis. It appears that cells of the immature cortex express a wide diversity of actors involved in Zn homeostasis with Zip7, SOD1, and metallothioneins being the most abundant transcripts throughout corticogenesis. The quantification of total Zn with XRF and ICP-AES reveals a reduction of Zn levels. Moreover, this is accompanied by a diminution of the size of the internal pools of mobilizable Zn. This study illustrates the tight temporal and spatial regulation of Zn homeostasis during cerebral brain development.
Published: 2019

17. Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells

Author: Jean-Michel Vallat, Katarzyna J .Radomska, Pierre Wolkenstein, Patrick Charnay, Amal Debbiche, Aurélie Gresset, Fanny Coulpier, Sophie Lemoine, Piotr Topilko, Alain Schmitt, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GenomiqueENS (Genomique ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Neurologie [CHU Limoges], CHU Limoges, and Thomas-Chollier, Morgane
Subjects: 0301 basic medicine, Cell type, Schwann cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease_cause, neurofibroma, 03 medical and health sciences, 0302 clinical medicine, Cellular origin, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Schwann cells, Allele, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Mutation, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Disease mechanisms, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], boundary caps, 030104 developmental biology, medicine.anatomical_structure, Oncology, NF1, Tumor progression, 030220 oncology & carcinogenesis, Genetically Engineered Mouse, Cancer research, Prss56
Abstract: Patients carrying an inactive NF1 allele develop tumors of Schwann cell origin called neurofibromas (NF). Genetically engineered mouse models have significantly enriched our understanding of plexiform forms of NFs (pNF). However, this has not been the case for cutaneous neurofibromas (cNF), observed in all NF1 patients, as no previous model recapitulates their development. Here, we show that conditional Nf1 inactivation in Prss56-positive boundary cap cells leads to bona fide pNFs and cNFs. This work identifies subepidermal glia as a likely candidate for the cellular origin of cNFs and provides insights on disease mechanisms, revealing a long, multistep pathologic process in which inflammation-related signals play a pivotal role. This new mouse model is an important asset for future clinical and therapeutic investigations of NF1-associated neurofibromas. Significance: Patients affected by NF1 develop numerous cNFs. We present a mouse model that faithfully recapitulates cNFs, identify a candidate cell type at their origin, analyze the steps involved in their formation, and show that their development is dramatically accelerated by skin injury. These findings have important clinical/therapeutic implications. This article is highlighted in the In This Issue feature, p. 1
Published: 2019

18. Interferon Regulatory Factor 5 represses oxidative respiration in human and murine macrophages by inhibition of mitochondrial matrix protein GHITM

Author: Sylvain Baulande, Corinne Blugeon, Jeremie Boucher, Marc Diedisheim, Charline Potier, Daniel Lindén, Alexandre Humbert, Lucie Orliaguet, Jessica Michieletto, François Fenaille, Judith Charbit, Laura G. Baudrin, Fawaz Alzaid, Akila Hamimi, Jean-Pierre Riveline, Jennifer Rieusset, Jean-Baptiste Julla, Florence Castelli, Sonia Lameiras, Raphaelle Ballaire, Sophie Lemoine, Jean-François Gautier, Nicolas Venteclef, Patricia Legoix, Tina Ejlalmanesh, and Antoine Soprani
Subjects: Mitochondrial matrix, Chemistry, Respiration, Oxidative phosphorylation, GHITM, Cell biology, Interferon regulatory factors
Abstract: Over the course of diet-induced obesity (DIO), adipose tissue macrophage (ATM) populations transition from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that the Interferon Regulatory Factor (IRF)-5 is a key molecular switch mediating repression of macrophage oxidative capacity early in DIO. ATMs from mice with a myeloid-specific deletion of IRF5 are characterised by increased mitochondrial activity and oxidative respiration compared to ATMs from wild-type mice. This hyper-oxidative phenotype is inducible and reversible in vitro by delivery of an inhibitory IRF5-decoy peptide and through IRF5 adenoviral over-expression, respectively. In a data-driven approach, using public IRF5-cistrome data and in-house RNA-sequencing, we identified a transcriptional mechanism by which cellular oxidative capacity is repressed in an IRF5-dependent manner. The hyper-oxidative phenotype of IRF5-deficient macrophages is mediated by the Growth Hormone Inducible Transmembrane Protein (GHITM), known for maintaining mitochondrial architecture for optimal oxidative respiration. Cas9-mediated simultaneous knock-down of GHITM and of IRF5 reverses the hyper-oxidative phenotype associated with IRF5-deficiency in vitro. IRF5-dependent regulation of GHITM expression and mitochondrial activity extends to human ATMs and monocytes from obese and diabetic patients.
Published: 2021

19. Comparative transcriptome analysis of goat (Capra hircus) adipose tissue reveals physiological regulation of body reserve recovery after the peak of lactation

Author: Yannick Faulconnier, Céline Boby, Fanny Coulpier, Sophie Lemoine, Patrice Martin, and Christine Leroux
Subjects: Mammary Glands, Animal, Adipose Tissue, Physiology, Gene Expression Profiling, Goats, Genetics, Animals, Lactation, Female, Transcriptome, Lipids, Molecular Biology, Biochemistry
Abstract: Adipose tissue is the energy storage organ providing energy to other tissues, including mammary gland, that supports the achievement of successive lactation cycles. Our objective was to investigate the ability of goats to restore body fat reserves by comparing lipogenic enzyme activities and by transcriptomic RNA-Seq data at two different physiological stages, mid- and post-lactation. Key lipogenic enzyme activities were higher in goat omental adipose tissue during mid-lactation (74 days in milk) than during the post-lactation period (300 days postpartum). RNA-Sequencing analysis revealed 19,271 expressed genes in the omental adipose tissue. The comparison between adipose transcriptome analysis from mid- and post-lactation goats highlighted 252 differentially expressed genes (p
Published: 2022

20. Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes

Author: Tristan Piolot, Maria Almonacid, Philippe Mailly, Adel Al Jord, Stephany El-Hayek, Marie-Hélène Verlhac, Kei Miyamoto, Alice Othmani, Auguste Genovesio, Fanny Coulpier, Sophie Lemoine, Raphaël Voituriez, Robert Grosse, Christophe Klein, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Kindai University, University of Freiburg [Freiburg], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Laboratoire de Physique Théorique de la Matière Condensée (LPTMC), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), sophie, lemoine, Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kinki University, Régulations et communications cellulaires (RCC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Virology Laboratory, Hôpital Rothchild, Physiopathologie des Maladies du Système Nerveux Central, 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF)-PSL Research University (PSL), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cytoplasm, Nuclear Envelope, [SDV]Life Sciences [q-bio], Mutant, Mice, Transgenic, nuclear dynamics, Biology, General Biochemistry, Genetics and Molecular Biology, mechano-transduction, Transcriptome, 03 medical and health sciences, F-actin, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, medicine, Animals, Molecular Biology, Actin, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [PHYS]Physics [physics], Cell Nucleus, 0303 health sciences, Cell Biology, mouse oocyte, Oocyte, bio-physics, Actins, Chromatin, Cell biology, Actin Cytoskeleton, Meiosis, medicine.anatomical_structure, Oocytes, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Nucleus, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Nucleus position in cells can act as a developmental cue. Mammalian oocytes position their nucleus centrally using an F-actin-mediated pressure gradient. The biological significance of nucleus centering in mammalian oocytes being unknown, we sought to assess the F-actin pressure gradient effect on the nucleus. We addressed this using a dedicated computational 3D imaging approach, biophysical analyses, and a nucleus repositioning assay in mouse oocytes mutant for cytoplasmic F-actin. We found that the cytoplasmic activity, in charge of nucleus centering, shaped the nucleus while promoting nuclear envelope fluctuations and chromatin motion. Off-centered nuclei in F-actin mutant oocytes were misshaped with immobile chromatin and modulated gene expression. Restoration of F-actin in mutant oocytes rescued nucleus architecture fully and gene expression partially. Thus, the F-actin-mediated pressure gradient also modulates nucleus dynamics in oocytes. Moreover, this study supports a mechano-transduction model whereby cytoplasmic microfilaments could modulate oocyte transcriptome, essential for subsequent embryo development.
Published: 2019

21. Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Play a Major Role in CD4+ T-Cell Impairment During Sepsis

Author: Tanguy Chaumette, Jeremie Poschmann, Fanny Coulpier, Sophie Lemoine, Antoine Asquier, Jocelyne Caillon, Emilie Ronin, Benoît L. Salomon, Benjamin Gaborit, Virginie Le Mabecque, David Boutoille, Marie Chauveau, Cédric Jacqueline, Mickael Vourc'h, Alexandre Bourdiol, Karim Asehnoune, Antoine Roquilly, Benoit Tessoulin, Abderrahmane Sadek, Marion Davieau, Alexis Broquet, Cédric Louvet, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique, Institut de Biologie de l’Ecole Normale Superieure, Paris, France
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Staphylococcus aureus, Secondary infection, medicine.medical_treatment, [SDV]Life Sciences [q-bio], chemical and pharmacologic phenomena, medicine.disease_cause, T-Lymphocytes, Regulatory, Sepsis, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Animals, Humans, Receptors, Tumor Necrosis Factor, Type II, Immunology and Allergy, Cells, Cultured, Immunosuppression Therapy, Mice, Knockout, Effector, business.industry, Immunosuppression, hemic and immune systems, medicine.disease, In vitro, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, CD4 Antigens, Immunology, Female, Tumor necrosis factor receptor 2, business
Abstract: Sepsis causes inflammation-induced immunosuppression with lymphopenia and alterations of CD4+ T-cell functions that renders the host prone to secondary infections. Whether and how regulatory T cells (Treg) are involved in this postseptic immunosuppression is unknown. We observed in vivo that early activation of Treg during Staphylococcus aureus sepsis induces CD4+ T-cell impairment and increases susceptibility to secondary pneumonia. The tumor necrosis factor receptor 2 positive (TNFR2pos) Treg subset endorsed the majority of effector immunosuppressive functions, and TNRF2 was particularly associated with activation of genes involved in cell cycle and replication in Treg, probably explaining their maintenance. Blocking or deleting TNFR2 during sepsis decreased the susceptibility to secondary infection. In humans, our data paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after culture in vitro with S. aureus. Our findings describe in vivo mechanisms underlying sepsis-induced immunosuppression and identify TNFR2pos Treg as targets for therapeutic intervention.
Published: 2020

22. Molecular characterisation of a cellular conveyor belt in Clytia medusae

Author: Michaël Manuel, Muriel Jager, Sophie Lemoine, Richard R. Copley, Corinne Blugeon, Thomas Condamine, Lucas Leclère, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Leclere, Lucas, École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL)
Subjects: Cnidaria, Tentacle, [SDV.BA] Life Sciences [q-bio]/Animal biology, Evolution, [SDV]Life Sciences [q-bio], Population, Gene Expression, Stem cells, Development, 03 medical and health sciences, Wnt, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, Medusa, education, Molecular Biology, Gene, Wnt Signaling Pathway, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Body Patterning, Cellular conveyor belt, 0303 health sciences, education.field_of_study, Polarity (international relations), Bilateral symmetry, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Wnt signaling pathway, Gene Expression Regulation, Developmental, Cell Biology, biology.organism_classification, Cell biology, [SDV] Life Sciences [q-bio], Hydrozoa, Cnidocyte, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; The tentacular system of Clytia hemisphaerica medusa (Cnidaria, Hydrozoa) has recently emerged as a promising experimental model to tackle the developmental mechanisms that regulate cell lineage progression in an early-diverging animal phylum. From a population of proximal stem cells, the successive steps of tentacle stinging cell (nematocyte) elaboration, are spatially ordered along a "cellular conveyor belt". Furthermore, the C. hemisphaerica tentacular system exhibits bilateral organisation, with two perpendicular polarity axes (proximo-distal and oral-aboral). We aimed to improve our knowledge of this cellular system by combining RNAseq-based differential gene expression analyses and expression studies of Wnt signalling genes. RNAseq comparisons of gene expression levels were performed (i) between the tentacular system and a control medusa deprived of all tentacles, nematogenic sites and gonads, and (ii) between three samples staggered along the cellular conveyor belt. The behaviour in these differential expression analyses of two reference gene sets (stem cell genes; nematocyte genes), as well as the relative representations of selected gene ontology categories, support the validity of the cellular conveyor belt model. Expression patterns obtained by in situ hybridisation for selected highly differentially expressed genes and for Wnt signalling genes are largely consistent with the results from RNAseq. Wnt signalling genes exhibit complex spatial deployment along both polarity axes of the tentacular system, with the Wnt/β-catenin pathway probably acting along the oral-aboral axis rather than the proximo-distal axis. These findings reinforce the idea that, despite overall radial symmetry, cnidarians have a full potential for elaboration of bilateral structures based on finely orchestrated deployment of an ancient developmental gene toolkit.
Published: 2019

23. The Tumor Microenvironment Impairs Th1 IFNγ Secretion through Alternative Splicing Modifications of

Author: Antoine, Bernard, Christophe, Hibos, Corentin, Richard, Etienne, Viltard, Sandy, Chevrier, Sophie, Lemoine, Joséphine, Melin, Etienne, Humblin, Romain, Mary, Théo, Accogli, Fanny, Chalmin, Mélanie, Bruchard, Paul, Peixoto, Eric, Hervouet, Lionel, Apetoh, François, Ghiringhelli, Frédérique, Végran, and Romain, Boidot
Subjects: Receptors, Interleukin-12, Th1 Cells, Gene Expression Regulation, Neoplastic, Alternative Splicing, Disease Models, Animal, Interferon-gamma, Mice, Cell Line, Tumor, Gene Knockdown Techniques, Neoplasms, RNA Precursors, Tumor Microenvironment, Animals, Humans, Protein Isoforms, Tumor Escape, RNA, Messenger, RNA-Seq, Promoter Regions, Genetic, Interferon Regulatory Factor-1
Abstract: It is clearly established that the immune system can affect cancer response to therapy. However, the influence of the tumor microenvironment (TME) on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect the immune system. Here, we showed that the TME, via a TGFβ-dependent mechanism, increased alternative splicing events and induced the expression of an alternative isoform of the IRF1 transcription factor (IRF1Δ7) in Th1 cells. We found that the SFPQ splicing factor (splicing factor, proline- and glutamine-rich) was responsible for the IRF1Δ7 production. We also showed, in both mice and humans, that the IRF1 alternative isoform altered the full-length IRF1 transcriptional activity on the
Published: 2019

24. Arabidopsis S2Lb links AtCOMPASS-like and SDG2 activity in H3K4me3 independently from histone H2B monoubiquitination

Author: Corinne Blugeon, Damarys Loew, Moussa Benhamed, Christophe Bailly, Fredy Barneche, Clara Bourbousse, Nicole Chaumont, Martin Rougée, Sophie Lemoine, David Latrasse, Chris Bowler, Anne-Flore Deton-Cabanillas, Gérald Zabulon, Anne-Sophie Fiorucci, Ammara Mohammad, Bérangère Lombard, Elodie Layat, Lorenzo Concia, Soon Kap Kim, David Stroebel, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement [Paris] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Agence Nationale pour la Recherche (ANR) [ANR-11-JSV2-003-01], Investissements d'Avenir program, ANR [ANR-10-LABX-54 MEMOLIFE, ANR-10-IDEX-0001-02 PSL], Universite Paris-Sud Doctoral School in Plant Sciences, Region Ile-de-France, Fondation pour la Recherche Medicale, 'Investissements d'Avenir' program [ANR-10-INBS-09], Fiorucci, Anne-Sophie, Bourbousse, Clara, Barneche, Fredy, Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement [IBPS] (LBD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), GenomiqueENS (Genomique ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Gestionnaire, HAL Sorbonne Université 5, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: lcsh:QH426-470, [SDV]Life Sciences [q-bio], Protein subunit, Saccharomyces cerevisiae, Arabidopsis, Histones, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Histone H2B, Monoubiquitination, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:QH301-705.5, Gene, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, biology, Research, Ubiquitination, biology.organism_classification, Arabidopsis/metabolism, Histone Methyltransferases/metabolism, Histones/metabolism, Cell biology, [SDV] Life Sciences [q-bio], lcsh:Genetics, lcsh:Biology (General), Histone methyltransferase, Histone Methyltransferases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], H3K4me3, 030217 neurology & neurosurgery
Abstract: Background The functional determinants of H3K4me3, their potential dependency on histone H2B monoubiquitination, and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike in Saccharomyces cerevisiae, where a single SET1 protein catalyzes H3K4me3 as part of COMPlex of proteins ASsociated with Set1 (COMPASS), in Arabidopsis thaliana, this activity involves multiple histone methyltransferases. Among these, the plant-specific SET DOMAIN GROUP 2 (SDG2) has a prominent role. Results We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. We show that S2Lb co-purifies with the AtCOMPASS core subunit WDR5, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes. S2Lb knockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. However, s2lb seedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2, or H3K4me3, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Conclusions Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been co-opted by the plant-specific SDG2 histone methyltransferase and mediates H3K4me3 deposition through an H2B monoubiquitination-independent pathway in Arabidopsis. Electronic supplementary material The online version of this article (10.1186/s13059-019-1705-4) contains supplementary material, which is available to authorized users.
Published: 2019

25. Arabidopsis S2Lb links AtCOMPASS-like and SDG2 activity in histone H3 Lys-4 trimethylation independently from histone H2B monoubiquitination

Author: David Latrasse, Ammara Mohammad, Bérangère Lombard, Christophe Bailly, Damarys Loew, Nicole Chaumont, Clara Bourbousse, Anne-Sophie Fiorucci, Chris Bowler, Sophie Lemoine, Soon Kap Kim, Martin Rougée, Anne-Flore Deton-Cabanillas, David Stroebel, Lorenzo Concia, Elodie Layat, Corinne Blugeon, Moussa Benhamed, Gérald Zabulon, and Fredy Barneche
Subjects: 0106 biological sciences, 0303 health sciences, biology, Protein subunit, biology.organism_classification, 01 natural sciences, Cell biology, 03 medical and health sciences, Histone H3, Histone methyltransferase, Arabidopsis, Histone H2B, H3K4me3, Monoubiquitination, WDR5, 030304 developmental biology, 010606 plant biology & botany
Abstract: The functional determinants of histone H3 Lys-4 trimethylation (H3K4me3), their potential dependency on histone H2B monoubiquitination (H2Bub) and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike inS. cerevisiae, where a single SET1 protein catalyzes H3 Lys-4 trimethylation as part of COMPASS (COMPlex of proteins ASsociated with Set1), inArabidopsis thalianathis activity involves multiple histone methyltransferases (HMTs). Among these, the plant-specific SDG2 (SET DOMAIN GROUP2) has a prominent role. We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. S2Lb co-purifies with the AtCOMPASS core subunit WDR5 from a high-molecular weight complex, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes.S2Lbknockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. Notwithstanding,s2lbseedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2 or H3 Lys-4 trimethylation, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been coopted by the plant-specific SDG2 HMT and mediates H3K4me3 deposition through an H2Bub-independent pathway in Arabidopsis.
Published: 2019

26. Aozan: an automated post-sequencing data-processing pipeline

Author: Sandrine Perrin, Stéphane Le Crom, Cyril Firmo, Sophie Lemoine, Laurent Jourdren, GenomiqueENS (Genomique ENS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse des Données à Haut Débit en Génomique (ADHDG), Evolution Paris Seine, Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Plateforme Génomique de l'IBENS, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université des Antilles (UA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and sophie, lemoine
Subjects: Quality Control, 0301 basic medicine, Statistics and Probability, Source code, Java, Computer science, media_common.quotation_subject, Data management, computer.software_genre, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Software, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Molecular Biology, License, computer.programming_language, media_common, business.industry, Sequence Analysis, DNA, Python (programming language), Computer Science Applications, Computational Mathematics, 030104 developmental biology, Computational Theory and Mathematics, chemistry, 030220 oncology & carcinogenesis, Operating system, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], business, computer, DNA
Abstract: Motivation Data management and quality control of output from Illumina sequencers is a disk space- and time-consuming task. Thus, we developed Aozan to automatically handle data transfer, demultiplexing, conversion and quality control once a run has finished. This software greatly improves run data management and the monitoring of run statistics via automatic emails and HTML web reports. Availability and Implementation Aozan is implemented in Java and Python, supported on Linux systems, and distributed under the GPLv3 License at: http://www.outils.genomique.biologie.ens.fr/aozan/. Aozan source code is available on GitHub: https://github.com/GenomicParisCentre/aozan.
Published: 2017

27. Active fluctuations modulate gene expression in mouse oocytes

Author: Raphaël Voituriez, Alice Othmani, Tristan Piolot, Isabelle Queguiner, Fanny Coulpier, Sophie Lemoine, Leïla Bastianelli, Stephany El-Hayek, Auguste Genovesio, Philippe Mailly, Maria Almonacid, Christophe Klein, and Marie-Hélène Verlhac
Subjects: 0303 health sciences, biology, Chemistry, RNA, Embryo, Oocyte, Cell biology, Chromatin, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Formins, Gene expression, biology.protein, medicine, Nucleus, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: In mammals, the nucleus is central in oocytes, not defining the future embryo axis. Nucleus centring depends on an F-actin mediated pressure gradient. InFmn2−/−oocytes, lacking the F-actin nucleator Formin 2, the nucleus is off-centre and can be centred by re-expressing Formin 2. Here, we addressed the biological significance of nucleus positioning in mammalian oocytes. Using a dedicated computational 3D imaging approach, we observed nuclear architecture alterations in mouseFmn2−/−oocytes. RNA sequencing of control versusFmn2−/−oocytes detected 2285 mis-regulated genes. Rescue experiments showed that the process of nuclear positioning impacts nuclear architecture and gene expression. Using signal processing methods coupled to biophysical modelling allowing the extraction ofin vivomechanical properties of the nuclear envelope, we showed that F-actin-mediated activity promotes nuclear envelope shape fluctuations and chromatin motion. We thus propose a mechano-transduction model whereby nucleus positioning via microfilaments modulates oocyte transcriptome, essential for further embryo development.
Published: 2018
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28. Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with

Author: Katarzyna J, Radomska, Fanny, Coulpier, Aurelie, Gresset, Alain, Schmitt, Amal, Debbiche, Sophie, Lemoine, Pierre, Wolkenstein, Jean-Michel, Vallat, Patrick, Charnay, and Piotr, Topilko
Subjects: Male, Mice, Knockout, Disease Models, Animal, Mice, Neurofibroma, Neurofibromatosis 1, Neurofibromin 1, Skin Neoplasms, Mutation, Animals, Female, Schwann Cells
Abstract: Patients carrying an inactive
Published: 2018

29. Active intermixing of indirect and direct neurons builds the striatal mosaic

Author: Ludmilla Lokmane, Maryama Keita, Caroline Mailhes, Kenneth Campbell, Marco A. Diana, Paloma Marchan-Sala, Daniela Popa, Rudolf Grosschedl, Sonia Garel, Benjamin Mathieu, Ildiko Györy, Fabien Mendary, Fanny Coulpier, Andrea Tinterri, Sophie Lemoine, HAL-UPMC, Gestionnaire, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), GenomiqueENS (Genomique ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Cincinnati Children's Hospital Medical Center, Albert-Ludwigs-Universität Freiburg, Boehringer Ingelheim, Ecole des Neurosciences de Paris Île de France (ENP), Ecole des Neurosciences de Paris, Neurosciences Paris Seine (NPS), Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Frieburg, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Functional features, Science, [SDV]Life Sciences [q-bio], Mutant, Striatum, Biology, Indirect pathway of movement, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Compartment (development), [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 10. No inequality, lcsh:Science, Transcription factor, 030304 developmental biology, Neurons, 0303 health sciences, Mutation, Cell Differentiation, Embryo, Mammalian, Mice, Inbred C57BL, Neostriatum, [SDV] Life Sciences [q-bio], Trans-Activators, Axon guidance, lcsh:Q, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, Gene Deletion, 030217 neurology & neurosurgery
Abstract: The striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments. While such cellular mosaic ensures the balanced activity of the two pathways, its developmental origin and pattern remains largely unknown. Here, we show that both SPN populations are specified embryonically and intermix progressively through multidirectional iSPN migration. Using conditional mutant mice, we found that inactivation of the dSPN-specific transcription factor Ebf1 impairs selective dSPN properties, including axon pathfinding, while molecular and functional features of iSPN were preserved. Ebf1 mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, highlighting that intermixing is a parallel process to compartment formation. Our study reveals while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture., Striatal projection neurons exist as two distinct classes and are anatomically mixed in the brain. Here, Tinterri and colleagues show the developmental mechanism of this cellular mosaicism that relies on an intrinsic transcription factor for cell type specification and intermixed cellular migration.
Published: 2018

30. Food group preferences and energy balance in moderately obese postmenopausal women subjected to brisk walking program

Author: Sophie Lemoine-Morel, Gérard Auneau, Pascale Mauriège, Karine Vallée, Sophie Garnier, Angelo Tremblay, Sandra Joffroy, and Vicky Drapeau
Subjects: medicine.medical_specialty, Physiology, Endocrinology, Diabetes and Metabolism, Energy balance, Walking, Body Mass Index, Food group, Food Preferences, Weight loss, Physiology (medical), Humans, Aerobic exercise, Medicine, Obesity, Aged, Brisk walking, Nutrition and Dietetics, business.industry, Cardiorespiratory fitness, General Medicine, Middle Aged, medicine.disease, Diet Records, Postmenopause, Menopause, Body Composition, Physical therapy, Female, Sedentary Behavior, medicine.symptom, Energy Intake, Energy Metabolism, business, Body mass index
Abstract: The objective of the study was to examine the effects of a 16-week walking program on food group preferences and energy balance of sedentary, moderately obese (body mass index, 29–35 kg/m2), postmenopausal Caucasian women, aged 60 ± 5 years old. One hundred and fifty-six volunteers were subjected to 3 sessions/week of 45 min of walking at 60% of heart rate reserve. Total energy intake (TEI) and food group preferences (3-day dietary record), total energy expenditure (TEE, 3-day physical activity diary), cardiorespiratory fitness (2-km walking test), anthropometry, and body composition (bioelectrical impedance) were measured before and after walking. Data were statistically analyzed using an ANOVA with repeated measures on 1 factor (time). The modest increase in TEE of 151 ± 24 kcal/day (p < 0.0001) leads to body weight, fat mass losses, and waist girth reduction (p < 0.0001). TEI remained unchanged despite a slight decrease in carbohydrate intake and a minor increase in protein intake (p < 0.05). Analysis of food records revealed a decreased consumption of fruits (p < 0.05) and sweet and fatty foods (p < 0.01), but an increase in oil consumption (p < 0.0001) after walking. Women with the highest body weight loss showed the greatest reduction in the consumption of fruits, sugar, sweet foods, and fatty foods (p < 0.05). Women with the greatest fat mass loss showed the highest decrease in fatty food intake (p < 0.05). In conclusion, although our walking program changed some food group consumption patterns, body weight loss was primarily because of the increased TEE.
Published: 2015

31. Beneficial effects of an intradialytic cycling training program in patients with end-stage kidney disease

Author: Bruno Pereira, Céline Coutard, Sophie Lemoine-Morel, Brice Martin, Myriam Rouchon-Isnard, Carole Groussard, Fanny Romain, Ludivine Malarde, Nathalie Boisseau, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ATMO Auvergne-Rhône-Alpes (ATMO-AURA), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, entraînement physique, Physiology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Physical fitness, Pilot Projects, condition physique, medicine.disease_cause, Absorptiometry, Photon, oxidative stress, Aged, 80 and over, Nutrition and Dietetics, medicine.diagnostic_test, néphropathie chronique, General Medicine, Middle Aged, Exercise Therapy, 3. Good health, Lipoproteins, LDL, lipid profile, Body Composition, Female, Training program, Adult, medicine.medical_specialty, Young Adult, Physiology (medical), Internal medicine, isoprostanes, medicine, Humans, In patient, End-stage kidney disease, Beneficial effects, Triglycerides, profil lipidique, Aged, Glutathione Peroxidase, Superoxide Dismutase, business.industry, Cholesterol, HDL, stress oxydatif, Cholesterol, LDL, medicine.disease, Bicycling, Exercise Test, physical fitness, Physical therapy, Kidney Failure, Chronic, Lipid Peroxidation, Lipid profile, business, exercise training, Biomarkers, chronic kidney disease, Oxidative stress, Kidney disease
Abstract: In chronic kidney disease (CKD), oxidative stress (OS) plays a central role in the development of cardiovascular diseases. This pilot program aimed to determine whether an intradialytic aerobic cycling training protocol, by increasing physical fitness, could reduce OS and improve other CKD-related disorders such as altered body composition and lipid profile. Eighteen hemodialysis patients were randomly assigned to either an intradialytic training (cycling: 30 min, 55%–60% peak power, 3 days/week) group (EX; n = 8) or a control group (CON; n = 10) for 3 months. Body composition (from dual-energy X-ray absorptiometry), physical fitness (peak oxygen uptake and the 6-minute walk test (6MWT)), lipid profile (triglycerides (TG), total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL)), and pro/antioxidant status (15-F2α-isoprostanes (F2-IsoP) and oxidized LDL in plasma; superoxide dismutase, glutathione peroxidase, and reduced/oxidized glutathione in erythrocytes) were determined at baseline and 3 months later. The intradialytic training protocol did not modify body composition but had significant effects on physical fitness, lipid profile, and pro/antioxidant status. Indeed, at 3 months: (i) performance on the 6MWT was increased in EX (+23.4%, p < 0.001) but did not change in CON, (ii) plasma TG were reduced in EX (–23%, p < 0.03) but were not modified in CON, and (iii) plasma F2-IsoP concentrations were lower in EX than in CON (–35.7%, p = 0.02). In conclusion, our results show that 30 min of intradialytic training, 3 times per week for 3 months, are enough to exert beneficial effects on the most sensitive and reliable marker of lipid peroxidation (IsoP) while improving CKD-associated disorders (lipid profile and physical fitness). Intradialytic aerobic cycling training represents a useful and easy strategy to reduce CKD-associated disorders. These results need to be confirmed with a larger randomized study.
Published: 2015

32. Dietary α-lactalbumin supplementation alleviates normocaloric western diet-induced glucose intolerance in Göttingen minipigs

Author: Lisa Pichon, Takashi Mikogami, Sophie Lemoine-Morel, Luz Lefeuvre, Arlette Gratas-Delamarche, Charles-Henri Malbert, Sophie Blat, and Sophie Vincent
Subjects: Lactalbumin, medicine.medical_specialty, Nutrition and Dietetics, Normal diet, medicine.diagnostic_test, business.industry, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Adipokine, Inflammation, medicine.disease_cause, medicine.disease, Obesity, Endocrinology, Internal medicine, Medicine, Secretion, medicine.symptom, business, Lipid profile, Oxidative stress
Abstract: Objective The pandemic of obesity in Western countries is mainly due to the high-fat, high-energy diet prevailing there. Obesity-associated metabolic disorders are the consequence of fat mass increase leading to altered adipokine secretion, hyperlipemia, oxidant stress, low-grade inflammation, and eventually glucose intolerance. Yet not all people consuming a Western diet become obese, and the question is raised whether these people are also at risk of developing metabolic disorders. Methods Glucose tolerance, lipid profile, and oxidant and inflammation status were investigated longitudinally in lean Gottingen minipigs receiving for 16 weeks either a normal diet (ND), a Western diet (WD), or a Western diet supplemented with a whey protein isolate (WPI) rich in α-lactalbumin known to improve glucose tolerance. ND and WD were supplied isoenergetically. Results Lean minipigs fed WD displayed glucose intolerance and altered lipid profile after 6 weeks of diet but no inflammation or oxidative stress. Supplementation with WPI alleviated glucose intolerance by improving insulin secretion, but not lipid profile. Conclusions Western diet consumption is deleterious for glucose tolerance even in the absence of fat mass accretion, and dyslipemia is a major determinant for this metabolic dysfunction. Stimulating insulin secretion with a WPI is an effective strategy to improve glucose tolerance.
Published: 2014

33. Quaking RNA-Binding Proteins Control Early Myofibril Formation by Modulating Tropomyosin

Author: François Xavier Dutrieux, Riadh Lobbardi, Sylvain Ernest, Fanny Coulpier, Frédéric M. Rosa, Sophie Lemoine, Aline Bonnet, Guillaume Lambert, sophie, lemoine, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Sarcomeres, Myofibril assembly, animal structures, muscle, RNA-binding protein, embryo, Embryonic Development, Tropomyosin, Biology, Myosins, myofibril, Muscle Development, Sarcomere, General Biochemistry, Genetics and Molecular Biology, Quaking, 03 medical and health sciences, Myofibrils, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Myocyte, Animals, RNA, Messenger, Molecular Biology, Zebrafish, 3' Untranslated Regions, Muscle Cells, Binding Sites, RNA, Gene Expression Regulation, Developmental, RNA-Binding Proteins, Cell Differentiation, Cell Biology, Zebrafish Proteins, musculoskeletal system, biology.organism_classification, 3. Good health, Cell biology, 030104 developmental biology, Biochemistry, Somites, embryonic structures, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Myofibril, Developmental Biology
Abstract: International audience; Skeletal muscle contraction is mediated by myofibrils, complex multi-molecular scaffolds structured into repeated units, the sarcomeres. Myofibril structure and function have been extensively studied, but the molecular processes regulating its formation within the differentiating muscle cell remain largely unknown. Here we show in zebrafish that genetic interference with the Quaking RNA-binding proteins disrupts the initial steps of myofibril assembly without affecting early muscle differentiation. Using RNA sequencing, we demonstrate that Quaking is required for accumulation of the muscle-specific tropomyosin-3 transcript, tpm3.12. Further functional analyses reveal that Tpm3.12 mediates Quaking control of myofibril formation. Moreover, we identified a Quaking-binding site in the 3' UTR of tpm3.12 transcript, which is required in vivo for tpm3.12 accumulation and myofibril formation. Our work uncovers a Quaking/Tpm3 pathway controlling de novo myofibril assembly. This unexpected developmental role for Tpm3 could be at the origin of muscle defects observed in human congenital myopathies associated with tpm3 mutation.
Published: 2016

34. Genome sequencing and transcriptome analysis of

Author: Christa, Ivanova, Jonas, Ramoni, Thiziri, Aouam, Alexa, Frischmann, Bernhard, Seiboth, Scott E, Baker, Stéphane, Le Crom, Sophie, Lemoine, Antoine, Margeot, and Frédérique, Bidard
Subjects: vib1, Research, Trichoderma reesei, Cellulase production, Promoter, Translocation, Genome analysis, Transcriptome
Abstract: Background The hydrolysis of biomass to simple sugars used for the production of biofuels in biorefineries requires the action of cellulolytic enzyme mixtures. During the last 50 years, the ascomycete Trichoderma reesei, the main source of industrial cellulase and hemicellulase cocktails, has been subjected to several rounds of classical mutagenesis with the aim to obtain higher production levels. During these random genetic events, strains unable to produce cellulases were generated. Here, whole genome sequencing and transcriptomic analyses of the cellulase-negative strain QM9978 were used for the identification of mutations underlying this cellulase-negative phenotype. Results Sequence comparison of the cellulase-negative strain QM9978 to the reference strain QM6a identified a total of 43 mutations, of which 33 were located either close to or in coding regions. From those, we identified 23 single-nucleotide variants, nine InDels, and one translocation. The translocation occurred between chromosomes V and VII, is located upstream of the putative transcription factor vib1, and abolishes its expression in QM9978 as detected during the transcriptomic analyses. Ectopic expression of vib1 under the control of its native promoter as well as overexpression of vib1 under the control of a strong constitutive promoter restored cellulase expression in QM9978, thus confirming that the translocation event is the reason for the cellulase-negative phenotype. Gene deletion of vib1 in the moderate producer strain QM9414 and in the high producer strain Rut-C30 reduced cellulase expression in both cases. Overexpression of vib1 in QM9414 and Rut-C30 had no effect on cellulase production, most likely because vib1 is already expressed at an optimal level under normal conditions. Conclusion We were able to establish a link between a chromosomal translocation in QM9978 and the cellulase-negative phenotype of the strain. We identified the transcription factor vib1 as a key regulator of cellulases in T. reesei whose expression is absent in QM9978. We propose that in T. reesei, as in Neurospora crassa, vib1 is involved in cellulase induction, although the exact mechanism remains to be elucidated. The data presented here show an example of a combined genome sequencing and transcriptomic approach to explain a specific trait, in this case the QM9978 cellulase-negative phenotype, and how it helps to better understand the mechanisms during cellulase gene regulation. When focusing on mutations on the single base-pair level, changes on the chromosome level can be easily overlooked and through this work we provide an example that stresses the importance of the big picture of the genomic landscape during analysis of sequencing data. Electronic supplementary material The online version of this article (doi:10.1186/s13068-017-0897-7) contains supplementary material, which is available to authorized users.
Published: 2016

35. Control of Plasma Membrane Permeability by ABC Transporters

Author: Sarah Brice Russo, W. Scott Moye-Rowley, Maitreya J. Dunham, L. Ashley Cowart, Frédéric Devaux, Svetlana Khakhina, Raman Manoharlal, Corinne Blugeon, Sophie Lemoine, Soraya S. Johnson, Anna B. Sunshine, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), NIH [GM49825], National Cancer Institute [F30 CA165440], National Institute on Aging [T32 AG000057], NIH, Yeast Resource Center [P41 GM103533], Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), 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)-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)-Centre National de la Recherche Scientifique (CNRS), University of Iowa [Iowa City], Medical University of South Carolina [Charleston] (MUSC), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), and sophie, lemoine
Subjects: Cell Membrane Permeability, Saccharomyces cerevisiae Proteins, Membrane lipids, [SDV]Life Sciences [q-bio], Mutant, ATP-binding cassette transporter, Saccharomyces cerevisiae, Biology, Microbiology, chemistry.chemical_compound, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene Expression Regulation, Fungal, Myriocin, Molecular Biology, ComputingMilieux_MISCELLANEOUS, myr, Articles, General Medicine, Flippase, Regulon, Biochemistry, chemistry, Trans-Activators, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ATP-Binding Cassette Transporters, Efflux, Transcription Factors
Abstract: ATP-binding cassette transporters Pdr5 and Yor1 from Saccharomyces cerevisiae control the asymmetric distribution of phospholipids across the plasma membrane as well as serving as ATP-dependent drug efflux pumps. Mutant strains lacking these transporter proteins were found to exhibit very different resistance phenotypes to two inhibitors of sphingolipid biosynthesis that act either late (aureobasidin A [AbA]) or early (myriocin [Myr]) in the pathway leading to production of these important plasma membrane lipids. These pdr5Δ yor1 strains were highly AbA resistant but extremely sensitive to Myr. We provide evidence that these phenotypic changes are likely due to modulation of the plasma membrane flippase complexes, Dnf1/Lem3 and Dnf2/Lem3. Flippases act to move phospholipids from the outer to the inner leaflet of the plasma membrane. Genetic analyses indicate that lem3 Δ mutant strains are highly AbA sensitive and Myr resistant. These phenotypes are fully epistatic to those seen in pdr5Δ yor1 strains. Direct analysis of AbA-induced signaling demonstrated that loss of Pdr5 and Yor1 inhibited the AbA-triggered phosphorylation of the AGC kinase Ypk1 and its substrate Orm1. Microarray experiments found that a pdr5Δ yor1 strain induced a Pdr1-dependent induction of the entire Pdr regulon. Our data support the view that Pdr5/Yor1 negatively regulate flippase function and activity of the nuclear Pdr1 transcription factor. Together, these data argue that the interaction of the ABC transporters Pdr5 and Yor1 with the Lem3-dependent flippases regulates permeability of AbA via control of plasma membrane protein function as seen for the high-affinity tryptophan permease Tat2.
Published: 2015

36. Role of the DHH1 Gene in the Regulation of Monocarboxylic Acids Transporters Expression in Saccharomyces cerevisiae

Author: Claire Torchet, Sandra Mota, Fanny Coulpier, Sophie Lemoine, Ana I. Pereira, Mathilde Garcia, Xavier Darzacq, Neide Vieira, Sandra Paiva, Agnès Le Saux, Lionel Benard, Frédéric Devaux, S. G. Barbosa, Thierry Delaveau, Margarida Casal, Department of Biology, University of Minho [Braga], Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes (LBMCE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virolle, Marie-Joelle, Repositório Científico do Instituto Politécnico do Porto, HAL UPMC, Gestionnaire, Universidade do Minho, Génomique des Microorganismes (LGM), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Expression Génétique Microbienne (EGM (UMR_8261 / FRE_3630)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), 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)-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)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Génomique des microorganismes, sophie, lemoine, Polytechnic Institute of Porto, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris
Subjects: Formates, [SDV]Life Sciences [q-bio], RNA Stability, Mutant, Messenger, lcsh:Medicine, Gene Expression, Biochemistry, DEAD-box RNA Helicases, Gene Expression Regulation, Fungal, Molecular Cell Biology, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Genetics, Regulation of gene expression, Multidisciplinary, biology, Symporters, Microbial Genetics, Adaptation, Physiological, Fungal, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Research Article, Monocarboxylic Acid Transporters, Saccharomyces cerevisiae Proteins, General Science & Technology, Physiological, Saccharomyces cerevisiae, Polysome, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Adaptation, Molecular Biology, Gene, Messenger RNA, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Biology and life sciences, Gene Expression Profiling, lcsh:R, Wild type, RNA, Cell Biology, biology.organism_classification, RNA processing, Gene Expression Regulation, Polyribosomes, Mutation, lcsh:Q, Genome-Wide Association Study
Abstract: Previous experiments revealed that DHH1, a RNA helicase involved in the regulation of mRNA stability and translation, complemented the phenotype of a Saccharomyces cerevisiae mutant affected in the expression of genes coding for monocarboxylic-acids transporters, JEN1 and ADY2 (Paiva S, Althoff S, Casal M, Leao C. FEMS Microbiol Lett, 1999, 170:301-306). In wild type cells, JEN1 expression had been shown to be undetectable in the presence of glucose or formic acid, and induced in the presence of lactate. In this work, we show that JEN1 mRNA accumulates in a dhh1 mutant, when formic acid was used as sole carbon source. Dhh1 interacts with the decapping activator Dcp1 and with the deadenylase complex. This led to the hypothesis that JEN1 expression is post-transcriptionally regulated by Dhh1 in formic acid. Analyses of JEN1 mRNAs decay in wild-type and dhh1 mutant strains confirmed this hypothesis. In these conditions, the stabilized JEN1 mRNA was associated to polysomes but no Jen1 protein could be detected, either by measurable lactate carrier activity, Jen1-GFP fluorescence detection or western blots. These results revealed the complexity of the expression regulation of JEN1 in S. cerevisiae and evidenced the importance of DHH1 in this process. Additionally, microarray analyses of dhh1 mutant indicated that Dhh1 plays a large role in metabolic adaptation, suggesting that carbon source changes triggers a complex interplay between transcriptional and post-transcriptional effects., This study was supported by the Portuguese grant POCI/BIA-BCM/57812/2004 (Eixo 2, Medida 2.3, QCAIII - FEDER). N.V. received a FCT PhD fellowship (SFRH/BD/23503/2005). S.M. received a FCT PhD fellowship (SFRH/BD/74790/2010). F.D.'s work is supported by a grant from the Agence pour la Recherche contre le Cancer (ARC). Support to C.B.M.A. by FEDER through POFC-COMPETE and by Portuguese funds from FCT through the project PEst-OE/BIA/UI4050/2014 is also acknowledged. The authors thank Josette Banroques and Kyle Tanner for their advice regarding polysome gradients. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2014

37. Oxidative stress, sarcopenia, antioxidant strategies and exercise: molecular aspects

Author: Thomas Brioche, Sophie Lemoine-Morel, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, medicine.medical_specialty, Antioxidant, antioxidant, muscle, medicine.medical_treatment, Biology, medicine.disease_cause, Muscle mass, Antioxidants, sarcopenia, 03 medical and health sciences, Internal medicine, Drug Discovery, medicine, Animals, Humans, oxidative stress, Pharmacology, exercise, aging, Protein turnover, medicine.disease, musculoskeletal system, Muscle atrophy, 3. Good health, body regions, Muscle regeneration, 030104 developmental biology, Endocrinology, Physical performance, Sarcopenia, medicine.symptom, human activities, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Sarcopenia could be currently defined as a geriatric syndrome initially characterized by a decrease in muscle mass that will get worse causing deterioration in strength and physical performance. A negative protein turnover, impaired mitochondrial dynamics and functions, a decreased muscle regeneration capacity, as well as an exacerbation of apoptosis are usually considered to be cellular mechanisms involved in muscle atrophy leading to sarcopenia. In this review, we first present that muscle overproduction of reactive oxygen and nitrogen species (RONS) and oxidative stress observed during aging are associated with sarcopenia, and the discuss how RONS are involved in redox-sensitive signaling pathways leading to sarcopenia. The identification of cost-effectiveness inter-ventions to maintain muscle mass and physical functions in the elderly is one of the most important public health challenges. Here, we also discuss about the efficiency of different kind of antioxidant strategies against sarcopenia. Since exercise is the best strategies to prevent and reverse sarcopenia, we also highlight that exercise acts as an antioxidant.
Published: 2016

38. Physiological and Toxic Effects of Purine Intermediate 5-Amino-4-imidazolecarboxamide Ribonucleotide (AICAR) in Yeast

Author: Bertrand Daignan-Fornier, Fanny Coulpier, Sophie Lemoine, Benoît Pinson, Christelle Saint-Marc, Barbara Simon-Kayser, Benoit Laloo, and Hans Caspar Hürlimann
Subjects: Purine, Ribonucleotide, Transcription, Genetic, Genes, Fungal, Saccharomyces cerevisiae, Genes, Recessive, Adenosine kinase, Biochemistry, Catalysis, Fungal Proteins, chemistry.chemical_compound, Species Specificity, Gene Expression Regulation, Fungal, Gene Regulation, Purine metabolism, Molecular Biology, Genes, Dominant, biology, Cell Biology, Ribonucleotides, Metabolic intermediate, Riboside, Alkaline Phosphatase, Aminoimidazole Carboxamide, biology.organism_classification, Models, Chemical, chemistry, Purines, Mutation, biology.protein, Nucleoside, Chromatography, Liquid
Abstract: 5-Amino-4-imidazolecarboxamide ribonucleotide 5′-phosphate (AICAR) is a monophosphate metabolic intermediate of the de novo purine synthesis pathway that has highly promising metabolic and antiproliferative properties. Yeast mutants unable to metabolize AICAR are auxotroph for histidine. A screening for suppressors of this phenotype identified recessive and dominant mutants that result in lowering the intracellular AICAR concentration. The recessive mutants affect the adenosine kinase, which is shown here to catalyze the phosphorylation of AICAR riboside in yeast. The dominant mutants strongly enhance the capacity of the alkaline phosphatase Pho13 to dephosphorylate 5-amino-4-imidazole N-succinocarboxamide ribonucleotide 5′-phosphate(SAICAR) into its non-toxic riboside form. By combining these mutants with transcriptomics and metabolomics analyses, we establish that in yeast responses to AICAR and SAICAR are clearly linked to the concentration of the monophosphate forms, whereas the derived nucleoside moieties have no effect even at high intracellular concentration. Finally, we show that AICAR/SAICAR concentrations vary under physiological conditions known to modulate transcription of the purine and phosphate pathway genes.
Published: 2011

39. Effets de l’entraînement de sprint et du désentraînement sur les variations du volume plasmatique induites par un test supramaximal chez des adolescents

Author: Hassane Zouhal, V Sophie, Sophie Lemoine-Morel, Maïtel Botcazou, A.B. Abderrahaman, Frédéric Derbré, and Christophe Jacob
Subjects: Orthopedics and Sports Medicine
Abstract: Resume Objectif Le but de ce travail est d’etudier l’influence d’un entrainement de sprint de six mois suivi de cinq mois de desentrainement sur les performances et les variations du volume plasmatique (ΔVP) estimees lors d’un test de sprint de six secondes chez des adolescents. Methodes Douze adolescents masculins, sans passe d’entrainement, ont participe a cette etude : un groupe de six sujets ayant suivi un entrainement de sprint de six mois (GE) et un groupe temoin de six sujets non entraines (GC). Un test de sprint de six secondes sur ergocyle a ete realise avant (P1) et apres entrainement (P2) dans les deux groupes et apres desentrainement pour GE. L’hematocrite (Ht) et les concentrations plasmatiques de lactate ([La]pl) ont ete mesurees au repos, apres l’echauffement, a l’arret de l’exercice et apres cinq et 20 minutes de recuperation. ΔPV a ete determine a partir de la variation de l’Ht. Resultats La puissance pic de pedalage augmente significativement chez GE a P2 (p Conclusion Cette etude montre que le programme d’entrainement propose n’a pas d’effet sur la diminution du VP observee apres un exercice de sprint de six secondes chez des adolescents.
Published: 2009

40. What is the influence of menopausal status on metabolic profile, eating behaviors, and perceived health of obese women after weight reduction?

Author: Eléonor Riesco, Sophie Garnier, Pascale Mauriège, Frédéric Sanguignol, Sophie Lemoine, and Michel RousselM. Roussel
Subjects: Gerontology, medicine.medical_specialty, Diet, Reducing, Physiology, Endocrinology, Diabetes and Metabolism, Physical exercise, Anxiety, Motor Activity, Blood serum, Weight loss, Physiology (medical), Weight Loss, medicine, Humans, Obesity, Exercise, Aged, Nutrition and Dietetics, Anthropometry, business.industry, Hemodynamics, Feeding Behavior, General Medicine, Middle Aged, Lipid Metabolism, medicine.disease, Menopause, Metabolism, Premenopause, Blood chemistry, Health, Body Composition, Physical therapy, Female, medicine.symptom, business, Body mass index, Stress, Psychological
Abstract: The duration of the numerous weight-loss studies that combine physical activity and diet varies from 3 to 14 months, and these studies have often considered pre- and postmenopausal women separately. The purpose of this study was to compare the effects of a 3-week weight-reducing program that combines caloric restriction and exercise on the metabolic profile, eating behaviors, and perceived health of sedentary obese pre- and postmenopausal women, after adjustment for age. In 10 pre- and 22 postmenopausal women, before and after weight loss, body composition, fasting lipid-lipoprotein profile, glucose and insulin levels, eating behaviors, and perceived health state were assessed. Body mass index, fat mass, and waist girth decreased after weight reduction in both groups (p < 0.0001). Reductions in fasting serum cholesterol and low-density lipoprotein-cholesterol levels were greater in pre- than in postmenopausal women (p < 0.0001), whereas triacylglycerol, glucose, and high-density lipoprotein-cholesterol levels decreased similarly in both groups (p < 0.05). Neither fasting insulin nor free fatty-acid concentrations were modified after weight loss in either group. Disinhibition (p < 0.005) and hunger scores on the three-factor eating questionnaire (TFEQ) (p < 0.05) and the state-anxiety score on the state–trait anxiety inventory (STAI) questionnaire (p < 0.0005) decreased in both groups, but restriction (TFEQ) increased (p < 0.01) and trait anxiety (STAI) decreased (p < 0.001) after weight reduction only in premenopausal women. Improvements in selected lipid-lipoprotein indices, eating behaviors, and perceived health-state components were better in pre- than in postmenopausal women, suggesting that menopausal status has an influence on some metabolic and behavioral responses to weight loss.
Published: 2008

41. Effect of weight reduction on quality of life and eating behaviors in obese women

Author: Pascale Mauriège, Frédéric Sanguignol, Nadia Rossell, Sophie Garnier, Sophie Lemoine, Vicky Drapeau, and Magali Poulain
Subjects: Adult, medicine.medical_specialty, Diet, Reducing, Psychometrics, Health Promotion, Body Mass Index, Quality of life, Endurance training, Weight loss, Surveys and Questionnaires, Internal medicine, Weight Loss, medicine, Humans, Obesity, Exercise, business.industry, Obstetrics and Gynecology, Feeding Behavior, Middle Aged, medicine.disease, Postmenopause, Menopause, Treatment Outcome, Endocrinology, Premenopause, Socioeconomic Factors, Disinhibition, Quality of Life, Lean body mass, Women's Health, Female, France, medicine.symptom, business, Body mass index, Demography
Abstract: Objective: To examine the impact of a 3-week weight-reducing program on body composition, physical condition, health-related quality of life, and eating behaviors of sedentary, obese (body mass index, 29-35 kg/m 2 ) women, according to menopausal status and menopause duration (
Published: 2007

42. High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

Author: Domenico Libri, Sophie Lemoine, Corinne Blugeon, Frédéric Devaux, Mathieu Rougemaille, Yves D'Aubenton‐Carafa, Sebastien Causse, Xavier Darzacq, John Mouaikel, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Plateforme Génomique de l'IBENS, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique des Microorganismes (LGM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Howard Hughes Medical Institute (HHMI), CNRS, Danish National Research Foundation, ANR [ANR-08-Blan-0038-01, ANR 2010-blan-1222-03], Association pour la Recherche sur le Cancer, GenomiqueENS (Genomique ENS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Aarhus University [Aarhus], Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), and sophie, lemoine
Subjects: Saccharomyces cerevisiae Proteins, Transcription, Genetic, THO complex, [SDV]Life Sciences [q-bio], Saccharomyces cerevisiae, Biology, DNA-binding protein, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Transcription (biology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene Expression Regulation, Fungal, Promoter Regions, Genetic, lcsh:QH301-705.5, Transcription factor, Gene, ChIA-PET, Heat-Shock Proteins, 030304 developmental biology, 0303 health sciences, 030302 biochemistry & molecular biology, Nuclear Proteins, Promoter, Molecular biology, Chromatin, Cell biology, DNA-Binding Proteins, lcsh:Biology (General), Ribonucleoproteins, Nuclear Pore, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Heat-Shock Response, Transcription Factors
Abstract: International audience; The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single-molecule fluorescence in situ hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase occupancy genome wide. We propose that the THO complex is required for tuning the dynamic of gene-nuclear pore association and mRNP release to the same high pace of transcription initiation.
Published: 2013

43. Effects of Acute Supramaximal Cycle Exercise on Plasma FFA Concentration in Obese Adolescent Boys

Author: Anne Paulin, Hassane Zouhal, Georges Jabbour, Jean-Marc Lavoie, Sophie Lemoine-Morel, Horia-Daniel Iancu, Université de Moncton, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-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)-Université de Brest (UBO)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Blood Glucose, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Energy metabolism, lcsh:Medicine, Overweight, Fatty Acids, Nonesterified, Insulin resistance, Sex Factors, Internal medicine, Blood plasma, medicine, Humans, Insulin, Obesity, lcsh:Science, Exercise, Multidisciplinary, business.industry, lcsh:R, Fatty Acids, medicine.disease, Endocrinology, Nonesterified, lcsh:Q, medicine.symptom, business, Energy Metabolism, Anaerobic exercise, Plasma ffa, Research Article
Abstract: International audience; AIMS: The aims of the present study are 1) to evaluate the free fatty acid (FFA) profile and 2) to determine the relative anaerobic and aerobic contributions to total energy consumption during repeated supramaximal cycling bouts (SCE) in adolescent boys with different body weight statuses. MATERIALS AND METHODS: Normal-weight (NW), overweight (OW), and obese (OB) adolescent boys (n =15 per group) completed a SCE sessions consisted of 6 x 6s maximal sprints with 2 min of passive rest between each repetition. Plasma FFA levels were determined at rest, immediately after a 10 min warm-up, and immediately at the end of SCE. The anaerobic and aerobic contributions (%) were measured via repeated SCE bouts. Insulin resistance was calculated using the homoeostatic model assessment (HOMA-IR) index. RESULTS: The FFA concentrations measured immediately after SCE were higher in the OB group than in the OW and NW (p\textless0.01 and p\textless0.01, respectively) groups. Moreover, the anaerobic contributions to SCE were significantly lower in obese adolescents (p\textless0.01) and decreased significantly during the 2nd, 3rd and 4th repetitions. The FFA levels were significantly associated with the HOMA-IR index and aerobic contribution among adolescent boys (r=0.83 and r=0.91, respectively, p\textless0.01). CONCLUSION: In contrast to the NW and OW groups, there is an increase in lipid mobilization and sift to aerobic energy metabolism during SCE in the OB group
Published: 2015

44. Effet d'une prise en charge pluridisciplinaire sur l'adiposité et la condition physique d'adolescent(e)s obèses

Author: E. Gonzalès, J.L. Roggero, Pascale Mauriège, S. Garnier, Sophie Lemoine, and S. Joffroy
Subjects: Orthopedics and Sports Medicine
Abstract: Resume Objectifs. – Cette etude s'interesse a l'effet d'une prise en charge pluridisciplinaire sur l'adiposite et la condition physique d'adolescent(e)s. Methodes. – Ces deux parametres ont ete mesures tous les mois, pendant dix mois. Resultats. – L'indice de masse corporelle (IMC) diminue similairement chez les deux sexes. La condition physique augmente au cours du temps. Une difference intersexe apparait en fin de sejour. Par ailleurs, l'evolution du poids des adolescent(e)s, durant le sejour, n'est pas liee a l'âge d'apparition de l'obesite. Aussi, le nombre de parents obeses n'induit pas de differences dans la perte de poids des adolescent(e)s, au cours du sejour. Conclusion. – Notre etude montre qu'une prise en charge pluridisciplinaire a des effets benefiques sur la sante.
Published: 2005

45. Estrogen Receptor Alpha mRNA in Human Skeletal Muscles

Author: Francoise Rannou-Bekono, Christophe Tiffoche, P. Granier, Marie-Lise Thieulant, Paul Delamarche, and Sophie Lemoine
Subjects: Adult, Male, medicine.medical_specialty, DNA, Complementary, medicine.drug_class, Receptor expression, Physical Therapy, Sports Therapy and Rehabilitation, Reference Values, Internal medicine, Deltoid muscle, medicine, Humans, Orthopedics and Sports Medicine, RNA, Messenger, Muscle, Skeletal, Electrophoresis, Agar Gel, Reverse Transcriptase Polymerase Chain Reaction, Chemistry, Estrogen Receptor alpha, Myometrium, Skeletal muscle, medicine.anatomical_structure, Endocrinology, Receptors, Estrogen, Estrogen, Agarose gel electrophoresis, Female, Nested polymerase chain reaction, Estrogen receptor alpha
Abstract: Introduction/purpose To explain the effect of estrogen on skeletal muscle, the presence of estrogen receptor alpha mRNA (ERalpha mRNA) was investigated in human skeletal muscle. Methods The highly sensitive technique of nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) was applied on a variety of tissue samples of both sexes: women (deltoid, pectoral, and uterus muscles) (N= 3) and men (deltoid muscle) (N= 3). The total ribonucleic acid was isolated from each tissue sample, reverse transcribed in a thermocycler, and nested PCR was then performed with specific primers. The by-products were analyzed by agarose gel electrophoresis. Internal standard 28S was simultaneously amplified. The ERalpha mRNA level was quantitated by using the ERalpha mRNA/28S mRNA ratio. Results The expected 204-bp product corresponding to ERalpha was amplified in all tested tissue samples, i.e., deltoid, pectoral, and uterine muscles from women and deltoid muscle from men. The ERalpha mRNA/28S mRNA ratios indicating the receptor expression levels in deltoid muscle from men and women were 0.945 +/- 0.393 (mean +/- SD) (N= 3) and 0.973 +/- 0.136 (mean +/- SD) (N= 2), respectively. Conclusions In conclusion, the nested RT-PCR technique identified the presence of transcript encoding ERalpha mRNA in human skeletal muscles. Semi-quantification did not reveal gender difference.
Published: 2003

46. Aerobic training suppresses exercise-induced lipid peroxidation and inflammation in overweight/obese adolescent girls

Author: Carole Groussard, Abdallah Fazah, Arlette Delamarche, Joël Pincemail, Sophie Lemoine-Morel, Christophe Jacob, Josiane Cillard, Jean-Claude Pineau, Elie Moussa, Hala Youssef, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Physical Therapy, Sports Therapy and Rehabilitation, Inflammation, Overweight, medicine.disease_cause, Lipid peroxidation, chemistry.chemical_compound, Young Adult, Internal medicine, medicine, Aerobic exercise, Humans, Orthopedics and Sports Medicine, Obesity, Exercise physiology, Young adult, Exercise, Peroxidase, business.industry, medicine.disease, Exercise Therapy, Oxidative Stress, Endocrinology, Treatment Outcome, chemistry, Pediatrics, Perinatology and Child Health, Body Composition, Female, Lipid Peroxidation, medicine.symptom, business, Oxidative stress, Biomarkers
Abstract: This study aimed to determine whether aerobic training could reduce lipid peroxidation and inflammation at rest and after maximal exhaustive exercise in overweight/obese adolescent girls. Thirty-nine adolescent girls (14-19 years old) were classified as nonobese or overweight/obese and then randomly assigned to either the nontrained or trained group (12-week multivariate aerobic training program). Measurements at the beginning of the experiment and at 3 months consisted of body composition, aerobic fitness (VO2peak) and the following blood assays: pre- and postexercise lipid peroxidation (15F2a-isoprostanes [F2-Isop], lipid hydroperoxide [ROOH], oxidized LDL [ox-LDL]) and inflammation (myeloperoxidase [MPO]) markers. In the overweight/obese group, the training program significantly increased their fat-free mass (FFM) and decreased their percentage of fat mass (%FM) and hip circumference but did not modify their VO2peak. Conversely, in the nontrained overweight/obese group, weight and %FM increased, and VO2peak decreased, during the same period. Training also prevented exercise-induced lipid peroxidation and/or inflammation in overweight/obese girls (F2-Isop, ROOH, ox-LDL, MPO). In addition, in the trained overweight/obese group, exercise-induced changes in ROOH, ox-LDL and F2-Isop were correlated with improvements in anthropometric parameters (waist-to-hip ratio, %FM and FFM). In conclusion aerobic training increased tolerance to exercise-induced oxidative stress in overweight/obese adolescent girls partly as a result of improved body composition.
Published: 2014

47. Endurance training and insulin therapy need to be associated to fully exert their respective beneficial effects on oxidant stress and glycemic regulation in diabetic rats

Author: Sophie Lemoine-Morel, Sophie Vincent, S. Le Douairon-Lahaye, M. S. Zguira, Arlette Gratas-Delamarche, Ludivine Malardé, Carole Groussard, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-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)-Université de Brest (UBO)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Blood Glucose, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], medicine.disease_cause, Biochemistry, Diabetes Mellitus, Experimental, Endurance training, Internal medicine, Diabetes mellitus, Physical Conditioning, Animal, medicine, Animals, Insulin, Treadmill, Rats, Wistar, Glycemic, 2. Zero hunger, Type 1 diabetes, Insulin glargine, business.industry, General Medicine, medicine.disease, 3. Good health, Rats, Oxidative Stress, Endocrinology, Physical Endurance, business, Oxidative stress, medicine.drug
Abstract: International audience; Abstract In type 1 diabetic subjects, hyperglycemia-induced oxidant stress (OS) plays a central role in the onset and development of diabetes complications. This study aimed to assess the benefits of an endurance training program and insulin therapy, alone or in combination, on the glycemic regulation, markers for OSand antioxidant system in diabetic rats. Forty male Wistar rats were divided into diabetic (D), insulin-treated diabetic (D-Ins), diabetic trained (D-Tr), or insulin-treated diabetic trained (D-Ins+ Tr) groups. An additional healthy group served as control group. Insulin therapy (Lantus, insulin glargine, Sanofi) and endurance training (a treadmill run of 60 min/day, 25 m/min, 5 days/week) were initiated 1 week after streptozotocin-induced diabetes (45 mg/kg) and lasted for 8 weeks. At the end of the protocol, blood glucose and fructosamine levels, markers for skeletal muscle OS (CML, isoprostanes, GSH/GSSG) and antioxidant system (SOD and GPx activity, ORAC) were assessed. In diabetic rats, the glycemic control was altered and OS marker levels were increased, while the antioxidant system activity remained unchanged. Insulin treatment improved the glycemic regulation, the pro-antioxidant statusand contributed to the reduction of OS marker levels. Endurance training decreased OS marker levels without improving the antioxidant enzyme activity. Endurance training and insulin therapy acted independently (by different ways), but their association prolonged the insulin action and allowed a better adaptation of the antioxidant system. To conclude, our results demonstrate that combination of insulin treatment and endurance training leads to greater benefits on the glycemic regulation and oxidant status.
Published: 2014

48. Exercise per se masks oral contraceptive-induced postprandial lipid mobilization

Author: Martine Duclos, Anne Meddahi-Pellé, Laurie Isacco, Sophie Lemoine-Morel, Nathalie Boisseau, David Thivel, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Clermont-Ferrand, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Blood Glucose, Glycerol, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Fatty Acids, Nonesterified, postprandial state, 0302 clinical medicine, Atrial natriuretic peptide, SUBSTRATE OXIDATION, Insulin, oral contraceptives, education.field_of_study, Nutrition and Dietetics, ATRIAL-NATRIURETIC-PEPTIDE, Anthropometry, exercise, Lipid Mobilization, Area under the curve, VO2 max, General Medicine, Postprandial Period, Postprandial, Body Composition, PROLONGED EXERCISE, Female, women, GLYCOGEN UTILIZATION, GROWTH-HORMONE, Adult, medicine.medical_specialty, lipolytic activity, Adolescent, MENSTRUAL-CYCLE PHASE, Population, FAT-OXIDATION, 030209 endocrinology & metabolism, LIPOPROTEIN-LIPASE, 03 medical and health sciences, Oxygen Consumption, Physiology (medical), Internal medicine, medicine, Humans, education, hormones, business.industry, 030229 sport sciences, Menstrual cycle phase, MODERATE-INTENSITY EXERCISE, Endocrinology, ENDURANCE EXERCISE, business, Energy Intake, Biomarkers, Hormone, Contraceptives, Oral
Abstract: Because of their hormonal content, oral contraceptives may alter lipolytic activity under resting or exercise conditions in women. The aim of the present study was to compare lipid mobilization in a postprandial state at rest and during exercise in oral contraceptive users (OC+) versus nonusers (OC–). The metabolic (glucose, glycerol, free fatty acids) and hormonal (insulin, atrial natriuretic peptide (ANP), growth hormone, insulin-like growth factor-1 (IGF-1), and catecholamines) concentrations were determined in 11 OC+ (monophasic low-dose oral contraceptives) and 10 OC– during a resting and an exercise session (45 min at 65% maximal oxygen consumption). Results were expressed as plasma concentrations and area under the concentration versus time curve values. ANP concentrations were higher in OC+ compared with OC– women at baseline (p = 0.04). Plasma concentrations of glycerol (p = 0.04), free fatty acids (p = 0.04), ANP (p = 0.02), and noradrenaline (p = 0.04) were higher in OC+ compared with OC– when both sessions were pooled. The plasma growth hormone, IGF-1, and adrenaline concentrations were not significantly different between the 2 groups. When the effect of exercise was isolated to overcome food intake and daytime variations (exercise per se using the area under the curve), no difference was observed between groups for all metabolic and hormonal variables. Overall, oral contraceptives increased lipid mobilization in the postprandial state, but this effect was blunted when lipolytic activity was stimulated by exercise per se. Oral contraceptive-induced greater lipolytic mobilization could be partly explained by greater ANP levels in OC users.
Published: 2014

49. Plasma volume variation with exercise: a crucial consideration for obese adolescent boys

Author: Daniel Curnier, Hassane Zouhal, Georges Jabbour, Marie-Eve Mathieu, Sophie Lemoine-Morel, Rami Jabbour, Université de Moncton, Département de kinésiologie, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-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)-Université de Brest (UBO)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Blood Glucose, Male, medicine.medical_specialty, Adolescent, Physiology, Endocrinology, Diabetes and Metabolism, Metabolite, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Overweight, Plasma volume, Body weight, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Power output, Lactic Acid, Obesity, Plasma Volume, Exercise, Nutrition and Dietetics, General Medicine, medicine.disease, Endocrinology, chemistry, Sprint, Plasma concentration, medicine.symptom
Abstract: International audience; Previous studies have demonstrated that considerable plasma volume variations (ΔPV) occur during and after exposure to different environmental and physiological conditions. Such changes have an important effect on plasma concentration of metabolite values. Currently, no study has examined ΔPV in individuals with different body weight status and used ΔPV to correct plasma solute values. The aims of this study were to assess (i) the effect of body weight status on ΔPV and (ii) the impact of these variations on lactate ([La]) and glucose ([Glu]) concentrations in normal-weight, overweight, and obese adolescent boys. Participants performed a cycling sprint test at their maximal power output. ΔPV were calculated using 2 methods, and both lactate and glucose concentrations were compared using total circulating values (T) and corrected values (cr) for ΔPV: [La]T vs. [La]cr and [Glu]T vs. [Glu]cr. Following exercise, ΔPV values decreased significantly from rest value and were higher in obese compared with overweight and normal-weight boys (p \textless 0.01). Moreover, ΔPV were correlated with body weight status (r = 0.85; p \textless 0.05). While [La]T and [Glu]T differed among the groups, no difference persisted when these values were corrected for ΔPV. The differences between total circulating and corrected values were significant. The impact of body weight status on ΔPV and thus on various plasma measures in response to exercise is important and should be considered in further studies
Published: 2014

50. THO/Sub2p Functions to Coordinate 3′-End Processing with Gene-Nuclear Pore Association

Author: Sophie Lemoine, Torben Heick Jensen, Jocelyne Boulay, Frédéric Devaux, Rajani Kanth Gudipati, Guennaelle Dieppois, Corinne Blugeon, Françoise Stutz, Domenico Libri, Mathieu Rougemaille, Elena Kisseleva-Romanova, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), IFR36, Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aarhus University [Aarhus], and sophie, lemoine
Subjects: Nucleocytoplasmic Transport Proteins, Transcription, Genetic, THO complex, RNA Transport, Saccharomyces cerevisiae/metabolism, 0302 clinical medicine, Transcription (biology), Heat-Shock Proteins/genetics, Nuclear pore, Heat-Shock Proteins, Adenosine Triphosphatases, Genetics, 0303 health sciences, biology, Ribonucleoproteins/metabolism, Nuclear Proteins, RNA-Binding Proteins, Nuclear Pore/metabolism, Nucleosomes/metabolism, Chromatin, Nucleosomes, Cell biology, medicine.anatomical_structure, Ribonucleoproteins, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA Polymerase II, Adenosine Triphosphatases/genetics/metabolism, RNA 3' End Processing, RNA, Fungal/metabolism, Saccharomyces cerevisiae Proteins, Active Transport, Cell Nucleus, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins/genetics/metabolism, General Biochemistry, Genetics and Molecular Biology, Chromatin/metabolism, 03 medical and health sciences, ddc:570, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Nuclear Proteins/metabolism, 030304 developmental biology, Biochemistry, Genetics and Molecular Biology(all), Helicase, RNA, RNA, Fungal, Cell nucleus, Nucleocytoplasmic Transport Proteins/metabolism, Mutation, Nuclear Pore, biology.protein, RNA-Binding Proteins/metabolism, RNA Polymerase II/metabolism, 030217 neurology & neurosurgery, Biogenesis
Abstract: International audience; During transcription, proteins assemble sequentially with nascent RNA to generate a messenger ribonucleoprotein particle (mRNP). The THO complex and its associated Sub2p helicase are functionally implicated in both transcription and mRNP biogenesis but their precise function remains elusive. We show here that THO/Sub2p mutation leads to the accumulation of a stalled intermediate in mRNP biogenesis that contains nuclear pore components and polyadenylation factors in association with chromatin. Microarray analyses of genomic loci that are aberrantly docked to the nuclear pore in mutants allowed the identification of approximately 400 novel validated target genes that require THO /Sub2p for efficient expression. Our data strongly suggests that the THO complex/Sub2p function is required to coordinate events leading to the acquisition of export competence at a step that follows commitment to 3'-processing.
Published: 2008

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