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1. Sequential Ras/MAPK and PI3K/AKT/mTOR pathways recruitment drives basal extrusion in the prostate-like gland of Drosophila

Author: Cyrille de Joussineau, Amandine Rambur, Yoan Renaud, Laurent Morel, Silvère Baron, Claude Beaudoin, Vincent Mirouse, Julio Buñay, Amalia Trousson, Jean-Marc A. Lobaccaro, Corinne Lours-Calet, Marine Vialat, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Bodescot, Myriam, This work was supported by CNRS, INSERM, Université Clermont Auvergne, GReD, La Ligue contre le cancer (C.J.) and Région Auvergne (Cancer Auvergne Prostate)., and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, MAPK/ERK pathway, Male, [SDV]Life Sciences [q-bio], Science, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Exocrine Glands, [SDV.CAN] Life Sciences [q-bio]/Cancer, Animals, Drosophila Proteins, Epidermal growth factor receptor, Autocrine signalling, Protein kinase A, Cancer models, lcsh:Science, Protein kinase B, PI3K/AKT/mTOR pathway, Multidisciplinary, Phosphoinositide 3-kinase, Prostate cancer, biology, Chemistry, TOR Serine-Threonine Kinases, Prostatic Neoplasms, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], General Chemistry, Cell biology, Insulin receptor, 030104 developmental biology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], 030220 oncology & carcinogenesis, biology.protein, Drosophila, lcsh:Q, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: One of the most important but less understood step of epithelial tumourigenesis occurs when cells acquire the ability to leave their epithelial compartment. This phenomenon, described as basal epithelial cell extrusion (basal extrusion), represents the first step of tumour invasion. However, due to lack of adequate in vivo model, implication of emblematic signalling pathways such as Ras/Mitogen-Activated Protein Kinase (MAPK) and phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathways, is scarcely described in this phenomenon. We have developed a unique model of basal extrusion in the Drosophila accessory gland. There, we demonstrate that both Ras/MAPK and PI3K/AKT/mTOR pathways are necessary for basal extrusion. Furthermore, as in prostate cancer, we show that these pathways are co-activated. This occurs through set up of Epidermal Growth Factor Receptor (EGFR) and Insulin Receptor (InR) dependent autocrine loops, a phenomenon that, considering human data, could be relevant for prostate cancer., The molecular mechanisms leading to basal extrusion are unclear. Here, the authors use the Drosophila accessory gland to model human prostate acini and show that Ras/MAPK and PI3K/AKT/mTOR pathways are co-activated in two autocrine loops by dEGF and dIGF, inducing basal extrusion and subsequent tumour formation.
Published: 2020

2. Drosophila Accessory Gland: A Complementary In Vivo Model to Bring New Insight to Prostate Cancer

Author: Amandine Rambur, Claude Beaudoin, Marine Vialat, Jean-Marc A. Lobaccaro, Cyrille de Joussineau, Corinne Lours-Calet, Laurent Morel, Silvère Baron, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
Subjects: QH301-705.5, [SDV]Life Sciences [q-bio], late tumorigenesis, Disease, Review, Bioinformatics, medicine.disease_cause, Prostate cancer, Human disease, Prostate, In vivo, Medicine, Biology (General), business.industry, in vivo model, Cancer, General Medicine, medicine.disease, prostate cancer, medicine.anatomical_structure, Drosophila, early tumorigenesis, Signal transduction, business, Carcinogenesis
Abstract: International audience; Prostate cancer is the most common cancer in aging men. Despite recent progress, there are still few effective treatments to cure its aggressive and metastatic stages. A better understanding of the molecular mechanisms driving disease initiation and progression appears essential to support the development of more efficient therapies and improve patient care. To do so, multiple research models, such as cell culture and mouse models, have been developed over the years and have improved our comprehension of the biology of the disease. Recently, a new model has been added with the use of the Drosophila accessory gland. With a high level of conservation of major signaling pathways implicated in human disease, this functional equivalent of the prostate represents a powerful, inexpensive, and rapid in vivo model to study epithelial carcinogenesis. The purpose of this review is to quickly overview the existing prostate cancer models, including their strengths and limitations. In particular, we discuss how the Drosophila accessory gland can be integrated as a convenient complementary model by bringing new understanding in the mechanisms driving prostate epithelial tumorigenesis, from initiation to metastatic formation.
Published: 2021

3. EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness

Author: Bruno Ragazzon, Jean-Christophe Pointud, Houda Tabbal, Pierre Val, Igor Tauveron, Coralie Drelon, M. Batisse-Lignier, Cyril Djari, Stéphanie Rodriguez, Anne-Marie Lefrançois-Martinez, Amandine Septier, Jérôme Bertherat, Guillaume Assié, Isabelle Sahut-Barnola, Mickael Mathieu, Antoine Martinez, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Cancer Research, Adenosine, Indoles, Cell Cycle Proteins, MESH: Adrenal Cortex Neoplasms, MESH: Mice, Knockout, MESH: Proportional Hazards Models, MESH: Adrenocortical Carcinoma, 0302 clinical medicine, Gene expression, Adrenocortical Carcinoma, E2F1, MESH: Animals, Mice, Knockout, MESH: Chromatin Immunoprecipitation, MESH: Indoles, Regulation of gene expression, biology, EZH2, MESH: Gene Expression Regulation, Neoplastic, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Ribonucleoside Diphosphate Reductase, 3. Good health, Gene Expression Regulation, Neoplastic, Securin, MESH: E2F1 Transcription Factor, Histone, Oncology, 030220 oncology & carcinogenesis, MESH: Computational Biology, Chromatin Immunoprecipitation, Ribonucleoside Diphosphate Reductase, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Article, Adrenal tumours, MESH: Multivariate Analysis, 03 medical and health sciences, MESH: Cell Cycle Proteins, Cancer epigenetics, MESH: Cell Proliferation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Enhancer of Zeste Homolog 2 Protein, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Transcription factor, Cell Proliferation, Proportional Hazards Models, MESH: Humans, Cell growth, Computational Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Adenosine, Adrenal Cortex Neoplasms, MESH: Securin, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Multivariate Analysis, biology.protein, Cancer research, Chromatin immunoprecipitation, E2F1 Transcription Factor
Abstract: International audience; BACKGROUND: EZH2 is overexpressed and associated with poor prognosis in adrenocortical carcinoma (ACC) and its inhibition reduces growth and aggressiveness of ACC cells in culture. Although EZH2 was identified as the methyltransferase that deposits the repressive H3K27me3 histone mark, it can cooperate with transcription factors to stimulate gene transcription. METHODS: We used bioinformatics approaches on gene expression data from three cohorts of patients and a mouse model of EZH2 ablation, to identify targets and mode of action of EZH2 in ACC. This was followed by ChIP and functional assays to evaluate contribution of identified targets to ACC pathogenesis. RESULTS: We show that EZH2 mostly works as a transcriptional inducer in ACC, through cooperation with the transcription factor E2F1 and identify three positive targets involved in cell cycle regulation and mitosis i.e., RRM2, PTTG1 and ASE1/PRC1. Overexpression of these genes is associated with poor prognosis, suggesting a potential role in acquisition of aggressive ACC features. Pharmacological and siRNA-mediated inhibition of RRM2 blocks cell proliferation, induces apoptosis and inhibits cell migration, suggesting that it may be an interesting target in ACC. CONCLUSIONS: Altogether, these data show an unexpected role of EZH2 and E2F1 in stimulating expression of genes associated with ACC aggressiveness. British Journal of Cancer https://doi.org/10.1038/s41416-019-0538-y BACKGROUND Adrenocortical carcinomas (ACC) are endocrine malignancies associated with dismal prognosis. At diagnosis, 80% of patients present metastases reducing the 5 years survival rate below 30% for most series.
Published: 2019

4. Ethanolic extract of Algerian propolis decreases androgen receptor transcriptional activity in cultured LNCaP cells

Author: Nada Zabaiou, Vincent Sapin, Julio Buñay-Noboa, Silvère Baron, Amalia Trousson, Allan Fouache, Amar Zellagui, Mesbah Lahouel, Geoffroy Marceau, Jean-Marc A. Lobaccaro, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Biochimie Médicale - Biologie Moleculaire, CHU Clermont-Ferrand, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Biochimie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Centre Hospitalier Universitaire de Clermont-Ferrand, and Université Clermont Auvergne (UCA)
Subjects: Male, Transcriptional Activation, 0301 basic medicine, Agonist, medicine.drug_class, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Antineoplastic Agents, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, urologic and male genital diseases, Biochemistry, Propolis, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Endocrinology, Cell Line, Tumor, LNCaP, medicine, Animals, Humans, Molecular Biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Reporter gene, Chemistry, Cell Cycle, Prostatic Neoplasms, Androgen Antagonists, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Bees, Cell cycle, medicine.disease, Androgen, 3. Good health, Androgen receptor, 030104 developmental biology, Gene Expression Regulation, Receptors, Androgen, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Anti-androgen activity
Abstract: Antiandrogens have a peculiar place in the treatment of metastatic prostate cancer by blocking the androgen receptor (AR). Unfortunately, aggressive tumors could rapidly develop into a castration resistant state. It is therefore essential to look for new molecules that are more effective, affecting not only the androgen signaling and with minimum undesirable effects. Natural products are an interesting source of new therapeutics, especially for cancer therapy as 70% of them have botanical origin. Based on an ethnobotany screening, we evaluated the effects of ethanolic extract of propolis (EEP) from Algeria on LNCaP cells. Results pointed out that EEP reduces the survival of LNCaP cells with an IC50 of 0.04 mg/ml, induces the apoptosis and blocks the cell cycle at G0/G1 phase. Interestingly, EEP decreased the accumulation of AR suggesting some anti-androgen activity. Indeed, secreted amount of the androgen target protein PSA was decreased when LNCaP cells were incubated with EEP, starting after 4 h of treatment. This anti-androgen activity was also shown on the androgen target genes Fkbp5 and Sgk1. Finally, the capacity of EEP to block AR functioning was demonstrated in transient transfections with human AR and the reporter gene ARE-tk-Luc. Propolis antagonizes the induction of the luciferase activity induced by the natural androgen DHT (10−8M) or the synthetic AR agonist R1881 (10-7M). Altogether, these results highlight the potential pharmacological effects of EEP in future treatments of prostate cancer.
Published: 2019

5. Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia

Author: Allison Voisin, Silvère Baron, Amandine Septier, Jean-Marc A. Lobaccaro, Ayhan Kocer, Gerhard Liebisch, Silke Matysik, Laura Bousset, Joelle Henry-Berger, Christelle Damon-Soubeyrant, Amandine Rambur, Vincent Sapin, Laurent Morel, Cyrille de Joussineau, Yoan Renaud, Julio Buñay, Amalia Trousson, Angélique De Haze, Marcus Höring, Rachel Guiton, Anne Fogli, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University Hospital Regensburg, Génétique, Reproduction et Développement (GReD), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and Assuncao de Carvalho, Manuela
Subjects: 0301 basic medicine, Male, Physiology, [SDV]Life Sciences [q-bio], Receptors, Cytoplasmic and Nuclear, Apoptosis, Biochemistry, Androgen deprivation therapy, Prostate cancer, White Blood Cells, Mice, 0302 clinical medicine, Prostate, Animal Cells, Immune Physiology, Neoplasms, Medicine and Health Sciences, Tumor Microenvironment, Biology (General), Reproductive System Procedures, Immune Response, Liver X Receptors, Innate Immune System, Cell Death, General Neuroscience, Prostate Cancer, Prostate Diseases, 3. Good health, medicine.anatomical_structure, Oncology, Cell Processes, 030220 oncology & carcinogenesis, Androgens, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Anatomy, Cellular Types, General Agricultural and Biological Sciences, Research Article, Mice, 129 Strain, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, QH301-705.5, Urology, Immune Cells, Immunology, Prostatitis, Inflammation, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Exocrine Glands, Signs and Symptoms, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, Castration, Liver X receptor, Tumor microenvironment, Blood Cells, General Immunology and Microbiology, Macrophages, Immunity, Biology and Life Sciences, Cancers and Neoplasms, Prostatic Neoplasms, Androgen Antagonists, Cell Biology, Molecular Development, medicine.disease, Androgen, Hormones, Mice, Inbred C57BL, Genitourinary Tract Tumors, Disease Models, Animal, 030104 developmental biology, Immune System, Cancer research, Prostate Gland, Clinical Medicine, Developmental Biology
Abstract: Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders., Mice lacking the liver X nuclear receptors (LXRs), crucial integrators of lipid metabolism, were used to study the response of the prostate to androgen deprivation. This reveals that lack of androgens leads to chronic inflammation due to impaired clearance of castration-induced apoptotic cells, allowing production of pro-inflammatory cytokines and promoting prostate neoplasia.
Published: 2020

6. FXRα modulates leydig cell endocrine function in mouse

Author: Laura Thirouard, Hélène Holota, Angélique De Haze, Françoise Caira, David H. Volle, Manon Garcia, Mélusine Monrose, Jean-Paul Saru, Claude Beaudoin, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), VOLLE, David, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CCSD, Accord Elsevier
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Receptors, Cytoplasmic and Nuclear, Gonadotropin-releasing hormone, Biochemistry, Mice, Follicle-stimulating hormone, Leydig cell, 0302 clinical medicine, Endocrinology, Nuclear receptors, Testis, Receptor, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.BDLR.RS] Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Leydig Cells, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV] Life Sciences [q-bio], hCG signaling, medicine.anatomical_structure, Hypothalamus, Pituitary Gland, Luteinizing hormone, Gonadal Hormones, Protein Binding, Signal Transduction, endocrine system, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030209 endocrinology & metabolism, Biology, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Anterior pituitary, Internal medicine, medicine, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Animals, Endocrine system, Molecular Biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 030104 developmental biology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Steroidogenesis, Gene Expression Regulation, Endocrine Cells
Abstract: International audience; The hypothalamic-pituitary axis exert a major control over endocrine and exocrine testicular functions. The hypothalamic-pituitary axis corresponds to a cascade with the Gonadotropin Releasing Hormone secreted by the hypothalamus, which stimulates the synthesis and the release of Luteinizing Hormone (LH) and Follicle Stimulating Hormone by the gonadotropic cells of the anterior pituitary. The LH signaling pathway controls the steroidogenic activity of the Leydig cells via the activation of the luteinizing hormone/choriogonadotropin receptor. In order to avoid a runaway system, sex steroids exert a negative feedback within hypothalamus and pituitary. Testicular steroidogenesis is locally controlled within Leydig cells. The present work reviews some local regulations of steroidogenesis within the Leydig cells focusing mainly on the roles of the Farnesoid-X-Receptor-alpha and its interactions with several orphan members of the nuclear receptor superfamily. Further studies are required to reinforce our knowledge of the regulation of testicular endocrine function, which is necessary to ensure a better understanding of fertility disorders and then proposed an adequate treatment of the diseases.
Published: 2020

7. DNA polymerase epsilon is required for heterochromatin maintenance in Arabidopsis

Author: Ángeles Gómez-Zambrano, David Latrasse, Steven E. Jacobsen, Thierry Pélissier, Amy Hesketh, Leticia López-González, Moussa Benhamed, Pierre Bourguet, Magdalena E. Potok, Olivier Mathieu, Magali Perez, Marie-Noëlle Pouch-Pélissier, Olivier Da Ines, Charles I. White, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Instituto de Bioquimica Vegetal y Fotosintesis (IBVF), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Molecular, Cell and Developmental Biology [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CNRS, Inserm, Universite Clermont Auvergne Region Auvergne-Rhone-Alpes European Molecular Biology Organization (EMBO) European Research Council (ERC)European CommissionI2ST 260742Ministere de l'education nationale, de l'enseignement superieur et de la recherche United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAR35 GM130272, Instituto de Bioquimica Vegetal y Fotosintesis, University of California-University of California, Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Howard Hughes Medical Institute (HHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), University of California, and White, Charles
Subjects: DNA Replication, 0106 biological sciences, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Euchromatin, Heterochromatin, Arabidopsis, DNA polymerase epsilon, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 01 natural sciences, Epigenesis, Genetic, Histones, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.GEN.GPL] Life Sciences [q-bio]/Genetics/Plants genetics, Gene Silencing, Epigenetics, Heterochromatin maintenance, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, DNA methylation, Silencing, Arabidopsis Proteins, Research, Cell Cycle, DNA replication, Replication stress, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA Polymerase II, Chromatin, Up-Regulation, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Cell biology, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, [SDV.BV.AP] Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 010606 plant biology & botany
Abstract: Background Chromatin organizes DNA and regulates its transcriptional activity through epigenetic modifications. Heterochromatic regions of the genome are generally transcriptionally silent, while euchromatin is more prone to transcription. During DNA replication, both genetic information and chromatin modifications must be faithfully passed on to daughter strands. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear. Results We isolate a strong hypomorphic Arabidopsis thaliana mutant of the POL2A catalytic subunit of DNA polymerase epsilon and show that POL2A is required to stabilize heterochromatin silencing genome-wide, likely by preventing replicative stress. We reveal that POL2A inhibits DNA methylation and histone H3 lysine 9 methylation. Hence, the release of heterochromatin silencing in POL2A-deficient mutants paradoxically occurs in a chromatin context of increased levels of these two repressive epigenetic marks. At the nuclear level, the POL2A defect is associated with fragmentation of heterochromatin. Conclusion These results indicate that POL2A is critical to heterochromatin structure and function, and that unhindered replisome progression is required for the faithful propagation of DNA methylation throughout the cell cycle.
Published: 2020

8. Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome

Author: Marilyne Lavergne, Corinne Belville, Héléna Choltus, Christelle Gross, Régine Minet-Quinard, Denis Gallot, Vincent Sapin, Loïc Blanchon, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Gynécologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), BLANCHON, LOIC, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0301 basic medicine, Mycoplasma salivarium, ved/biology.organism_classification_rank.species, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pyrin domain, 0302 clinical medicine, fetal membranes, Pregnancy, amnion epithelial cells, Immunology and Allergy, Receptor, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Original Research, Mycoplasma fermentans, biology, Amnion, Chemistry, Caspase 1, Inflammasome, Blot, medicine.anatomical_structure, Host-Pathogen Interactions, Female, Pregnancy Trimesters, Oligopeptides, medicine.drug, Signal Transduction, lcsh:Immunologic diseases. Allergy, Immunology, mycoplasmas, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, NLRP7, Diglycerides, 03 medical and health sciences, medicine, Humans, inflammasomes, Adaptor Proteins, Signal Transducing, ved/biology, Cesarean Section, Parturition, Epithelial Cells, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Molecular biology, CARD Signaling Adaptor Proteins, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, inflammation, FSL-1, CARD domain, lcsh:RC581-607, 030215 immunology
Abstract: Context and Objectives: Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. Methods: The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of Mycoplasma salivarium and Mycoplasma fermentans in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a M. salivarium-derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. Results: NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, M. salivarium and M. fermentans were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Conclusion: Two new mycoplasmas, M. salivarium and M. fermentans, were identified in human fetal membranes, and a lipopeptide derived from M. salivarium was found to induce NLRP7 inflammasome formation in AECs.
Published: 2020

9. Methyl-donor supplementation prevents intestinal colonization by Adherent-invasive E. coli in a mouse model of crohn's disease

Author: Mélissa Chervy, Jérémy Denizot, Allison Agus, Elodie Gimier, Emilie Vazeille, Régine Minet-Quinard, Maud Privat, Sandrine Viala, Adeline Sivignon, Anthony Buisson, Elisabeth Billard, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Ministere de la Recherche et de la Technologie, Inserm Ministere de la Recherche et de la Technologie, INRAe Region Auvergne-Rhone-Alpes FEDER (AAP Nouveau Chercheur) 1640NCAA-AV0016772Fondation pour la Recherche Medicale (FRM, 'Contrat doctoral') ECO201906008953National Program 'Microbiote' Inserm Association Francois Aupetit (AFA), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Ministere de la Recherche et de la Technologie, Inserm Ministere de la Recherche et de la Technologie, INRAe Region Auvergne-Rhone-Alpes FEDER (AAP Nouveau Chercheur) 1640NCAA-AV0016772Fondation pour la Recherche Medicale (FRM, 'Contrat doctoral') ECO201906008953French government IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25)National Program 'Microbiote' Inserm Association Francois Aupetit (AFA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Denizot, Jérémy, and CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID
Subjects: Male, 0301 basic medicine, lcsh:Medicine, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Bacterial Adhesion, Transcriptome, Mice, chemistry.chemical_compound, 0302 clinical medicine, Crohn Disease, Intestinal Mucosa, Promoter Regions, Genetic, lcsh:Science, Escherichia coli Infections, 2. Zero hunger, Regulation of gene expression, Crohn's disease, Multidisciplinary, Cell adhesion molecule, 3. Good health, Female, 030211 gastroenterology & hepatology, Vitamin, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, GPI-Linked Proteins, Article, Microbiology, 03 medical and health sciences, Antigen, Antigens, CD, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Escherichia coli, medicine, Animals, Humans, Cellular microbiology, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Food, Formulated, lcsh:R, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, DNA Methylation, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Disease Models, Animal, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Gene Expression Regulation, chemistry, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Preclinical research, lcsh:Q, Bacterial infection, Calprotectin, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell Adhesion Molecules, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Deficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-Invasive Escherichia coli (AIEC) are frequently observed in Crohn’s disease (CD) patients. AIEC bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. Transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn’s disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients.
Published: 2020

10. Trapping a somatic endogenous retrovirus into a germline piRNA cluster immunizes the germline against further invasion

Author: Duc, Céline, Yoth, Marianne, Jensen, Silke, Mouniée, Nolwenn, Bergman, Casey M., Vaury, Chantal, Brasset, Emilie, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Genetics, University of Cambridge [UK] (CAM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)
Subjects: endocrine system, Inheritance, Germline, Retroelements, lcsh:QH426-470, urogenital system, Research, [SDV]Life Sciences [q-bio], Ovary, piRNA cluster, lcsh:Genetics, Drosophila melanogaster, lcsh:Biology (General), piRNAs, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genome stability, Animals, Female, Drosophila, RNA, Small Interfering, Transposable elements, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS
Abstract: Background For species survival, the germline must faithfully transmit genetic information to the progeny. Transposable elements (TEs) constitute a significant threat to genome stability due to their mobility. In the metazoan germline, their mobilization is limited by a class of small RNAs called PIWI-interacting RNAs (piRNAs) produced by dedicated genomic loci called piRNA clusters. Although the piRNA pathway is an adaptive genomic immunity system, it remains unclear how the germline gains protection from a new transposon invasion. Results To address this question, we analyze Drosophila melanogaster lines harboring a deletion within flamenco, a major piRNA cluster specifically expressed in somatic follicular cells. This deletion leads to derepression of the retrotransposon ZAM in the somatic follicular cells and subsequent germline genome invasion. In this mutant line, we identify de novo production of sense and antisense ZAM-derived piRNAs that display a germinal molecular signature. These piRNAs originated from a new ZAM insertion into a germline dual-strand piRNA cluster and silence ZAM expression specifically in germ cells. Finally, we find that ZAM trapping in a germinal piRNA cluster is a frequent event that occurs early during the isolation of the mutant line. Conclusions Transposons can hijack the host developmental process to propagate whenever their silencing is lost. Here, we show that the germline can protect itself by trapping invading somatic-specific TEs into germline piRNA clusters. This is the first demonstration of “auto-immunization” of a germline endangered by mobilization of a surrounding somatic TE. Electronic supplementary material The online version of this article (10.1186/s13059-019-1736-x) contains supplementary material, which is available to authorized users.
Published: 2019

11. Serum soluble receptor for advanced glycation end-products during acute bronchiolitis in infant: Prospective study in 93 cases

Author: Karen Coste, Emmanuelle Rochette, Aurélien Mulliez, Matthieu Jabaudon, Vincent Sapin, Laurence Roszyk, André Labbé, Carole Egron, CHU Clermont-Ferrand, Pôle Pédiatrie, Centre Hospitalier Universitaire [Rennes], Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, Délégation à la recherche clinique et aux innovations (DRCI), CHU de Clermont-Ferrand, Laboratoires d'Anatomie pathologique et de Physiologie, Université d'Auvergne - Clermont-Ferrand I (UdA), Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Biochimie, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, ARDS, MESH: Respiratory Sounds, Receptor for Advanced Glycation End Products, MESH: Bronchiolitis, Infection and Immunity, MESH: Hospitalization, Severity of Illness Index, Gastroenterology, Pathogenesis, 0302 clinical medicine, Recurrence, Prospective Studies, Respiratory system, soluble receptor for advanced glycation end-products, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, blood and urine biomarkers, infants, Prognosis, MESH: Infant, 3. Good health, Hospitalization, Acute Disease, Bronchiolitis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Acute Disease, Biomarker (medicine), Female, Original Article, Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV.BDLR.RA]Life Sciences [q-bio]/Reproductive Biology/Asexual reproduction, MESH: Prognosis, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, soluble receptor for advanced glycation end‐products, recurrent wheezing, MESH: Severity of Illness Index, Internal medicine, Lower respiratory tract infection, medicine, Humans, Respiratory Sounds, Asthma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, MESH: Receptor for Advanced Glycation End Products, business.industry, Infant, Original Articles, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Recurrence, 030104 developmental biology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, MESH: Biomarkers, lower respiratory tract infection, business, MESH: Female, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction Acute bronchiolitis is a major cause of acute respiratory distress in infants. The soluble receptor for advanced glycation end‐products (sRAGE) is a biomarker of pulmonary damage processes, with a diagnostic and a prognostic value in acute respiratory distress syndrome (ARDS). The RAGE pathway is also implicated in the pathogenesis of other respiratory diseases like asthma, but the value of sRAGE levels in acute bronchiolitis remains under‐investigated. Material and methods A prospective, observational, and analytical study was conducted at Clermont‐Ferrand University Hospital. The main objective was to evaluate the correlation between serum sRAGE and clinical severity of bronchiolitis in hospitalized infants aged
Published: 2018

12. Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit fetuses

Author: Delabaere, Amélie, Delabaere, Amelie, Blanchon, Loïc, Coste, Karen, Clairefond, Gael, Belville, Corinne, Blanc, Pierre, Marceau, Geoffroy, Sapin, Vincent, Gallot, Denis, Thérapie guidée par l'image (TGI), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Génétique, Reproduction et Développement (GReD), Chercheur indépendant, Laoratoire de Biochimie, CHU Clermont-Ferrand, Laboratoire de Biochimie, Pôle Entrepreneuriat et Innovation - Rouen Business School, Rouen Business School, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Clermont-Ferrand, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), and Centre Hospitalier Universitaire de Clermont-Ferrand
Subjects: Pathology, medicine.medical_specialty, Side effect, Retinoic acid, Connective tissue, Antineoplastic Agents, Apoptosis, Tretinoin, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, 030225 pediatrics, medicine, Animals, Diaphragmatic hernia, Lung, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Hernia, Diaphragmatic, Fetus, business.industry, Fetoscopy, Obstetrics and Gynecology, Congenital diaphragmatic hernia, Pulmonary Surfactants, Histology, respiratory system, medicine.disease, Elastin, 3. Good health, Trachea, Fetal Diseases, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Female, Collagen, Rabbits, business
Abstract: INTRODUCTION Lung hypoplasia and pulmonary arterial hypertension in congenital diaphragmatic hernia lead to a high perinatal mortality. Although sustained fetoscopic tracheal occlusion (TO) improves lung development, a major side effect is abnormal pneumocyte differentiation. This study evaluated the potential ability of intratracheal retinoic acid (RA) administration to reduce adverse effects of sustained TO in a rabbit model of diaphragmatic hernia. METHODS A left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits. On day 28, the same rabbits underwent sham surgery or TO, with an injection of empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the lungs were processed for histology, immunohistochemistry, and gene expression quantification. RESULTS A tracheal RA injection at the time of TO had no effect on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue composition. Retinoic acid plus TO had synergic effects on vascular measurements, proportional medial thickness, and endothelin-1 receptor type-A gene expression. The most noticeable effect was recovery of normal pneumocyte differentiation. CONCLUSION Retinoic acid plus TO prevented abnormal pneumocyte differentiation and seemed to have a beneficial effect on pulmonary vascularization.
Published: 2018

13. Comprehensive overview of murine epididymal mononuclear phagocytes and lymphocytes: Unexpected populations arise

Author: Joelle Henry-Berger, Marjorie Whitfield, Rachel Guiton, Joël R. Drevet, Chantal Goubely, Christelle Damon-Soubeyrand, Allison Voisin, Fabrice Saez, Ayhan Kocer, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Clermont Université, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), and Institut National de la Recherche Agronomique (INRA)
Subjects: Male, 0301 basic medicine, Immunology, Double negative, Cell Separation, Adaptive Immunity, Biology, Immunofluorescence, Monocytes, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Flow cytometry, Mice, 03 medical and health sciences, Immune system, Immunity, Immune Tolerance, medicine, Animals, Immunology and Allergy, Lymphocytes, ComputingMilieux_MISCELLANEOUS, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, Epididymis, Mice, Inbred BALB C, Phagocytes, medicine.diagnostic_test, Macrophages, Obstetrics and Gynecology, Receptors, Antigen, T-Cell, gamma-delta, Dendritic Cells, Flow Cytometry, Spermatozoa, Sperm, Immunity, Innate, Epithelium, Cell biology, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Reproductive Medicine
Abstract: Despite increasing evidence that epididymal immune disorders can lead to infertility, the cells and mechanisms underlying epididymal immunity remain poorly understood. In this study, we propose a rather exhaustive overview of innate and adaptive immune cells present in the murine caput and cauda epididymis. Using flow cytometry and a wide set of markers, we screened the broadest panel of immune cells ever, in this organ. For the first time, we unequivocally quantified the innate populations of monocytes, macrophages, and dendritic cells subtypes. We also revealed the presence of B cells, gamma delta T cells, and double negative T cells in the murine epididymis. They were localized by immunofluorescence stainings, and appeared to be all present in the interstitium and epithelium along the organ, but with respective preferential regional distribution. Altogether, these findings provide new insights on the actors and potential mechanisms involved in the immune responses against genital tract ascending pathogens and in the setting and maintenance of tolerance toward the sperm cells.
Published: 2018

14. RAGE inhibition reduces acute lung injury in mice

Author: Raiko, Blondonnet, Jules, Audard, Corinne, Belville, Gael, Clairefond, Jean, Lutz, Damien, Bouvier, Laurence, Roszyk, Christelle, Gross, Marilyne, Lavergne, Marianne, Fournet, Loic, Blanchon, Caroline, Vachias, Christelle, Damon-Soubeyrand, Vincent, Sapin, Jean-Michel, Constantin, Matthieu, Jabaudon, Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Université de Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Male, Biopsy, Science, Acute Lung Injury, Receptor for Advanced Glycation End Products, Anti-Inflammatory Agents, Gene Expression, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Ion Channels, Article, Mice, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Blood-Air Barrier, Antibodies, Monoclonal, respiratory system, Immunohistochemistry, Disease Models, Animal, Alveolar Epithelial Cells, Cytokines, Medicine, Blood Gas Analysis, Inflammation Mediators, Biomarkers
Abstract: International audience; The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)−5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair. Acute respiratory distress syndrome (ARDS) is a syndrome of diffuse inflammatory lung injury with increased pulmonary oedema and the rapid onset of hypoxemic respiratory failure 1. ARDS is still undertreated 2 , with high mortality and few effective therapies 3-5. RAGE is a membrane receptor that is expressed in alveolar type (AT)-1 epithelial cells of the lung and a marker of epithelial injury 6. There are many RAGE ligands, including high-mobility group box 1 protein (HMGB1), advanced glycation end-products (AGEs) and S100 protein 7, 8. RAGE controls a variety of cellular processes such as cell proliferation and migration, inflammation, apoptosis and microtubule stabilization 9. Its main soluble forms, referred to as soluble RAGE (sRAGE), include the extra-cellular domain of membrane RAGE (mRAGE) which is cleaved by proteinases and endogenous secretory RAGE (esRAGE, produced after alternative splicing) 10. In clinical ARDS, sRAGE has good diagnostic value and is associated with lung injury severity, impaired alveolar fluid clearance (AFC) and prognosis 6, 11-13. Impaired AFC is a major feature of ARDS that contributes to mortality 14. The main mechanism responsible for the resolution of alveolar oedema is ion transport across the alveolar epithelium, primarily through epithe-lial sodium (ENaC), Na,K-ATPase and aquaporin (AQP)-5 channels, thus creating a local osmotic gradient to reabsorb the water fraction of the oedema fluid from the airspaces of the lungs 15-17. Recent data support an effect of RAGE activation on ENaC activity in cultured AT-1 cells 18. However, in contrast to the situation in mice, the clearance of alveolar fluid after birth in humans may not critically depend on ENaC, at least in part because of greater reliance on other epithelial channels 15. The modulation of RAGE may reduce inflammatory responses in several models 19. Intratracheal administration of HMGB1 induced lung injury in mice and the pathological effects of intratracheal lipopolysaccharide (LPS) were partially ameliorated by systemic administration of anti-HMGB1 antibodies 8 , thereby implicating pattern-recognition receptors such as RAGE or toll-like receptors in the pathogenesis of ARDS. Experimental murine pulmonary ischemia followed by reperfusion caused lung injury that was ameliorated in mice treated with sRAGE and in RAGE −/− mice 20. Using a mouse model of lung
Published: 2017

15. Beyond mice: Emerging and transdisciplinary models for the study of early-onset myopathies

Author: Sylvie Hénon, Krzysztof Jagla, Sabrina Batonnet-Pichon, Benoit Kalman, Thomas Boudou, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire des matériaux et du génie physique (LMGP ), Institut National Polytechnique de Grenoble (INPG)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Boudou, Thomas, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA), 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)-Université Paris Cité (UPCité), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Matière et Systèmes Complexes (MSC)
Subjects: 0301 basic medicine, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Mechanotransduction, Interdisciplinary Studies, Skeletal muscle models, Mice, 03 medical and health sciences, Animal model, Muscular Diseases, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Epigenetics, Age of Onset, Zebrafish, Early onset, Potential impact, Tissue Engineering, biology, Early onset myopathies, Cell Biology, Anatomy, biology.organism_classification, Biomechanical Phenomena, 3. Good health, Structure and function, Disease Models, Animal, 030104 developmental biology, Drosophila, Neuroscience, Developmental Biology
Abstract: International audience; The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early-onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early-onset myopathies. However strategies based on simple animal models and on transdisciplinary approaches exploring mechanical muscle cell properties emerge as attractive, non-exclusive alternatives. These new ways provide valuable opportunities to improve our knowledge on how mechanical, biochemical, and genetic/epigenetic cues modulate the formation, organization and function of muscle tissues. Here we provide an overview of how single cell and micro-tissue engineering in parallel to non-mammalian, Drosophila and zebrafish models could contribute to filling gaps in our understanding of pathogenic mechanisms underlying early-onset myopathies. We also discuss their potential impact on designing new diagnostic and therapeutic strategies.
Published: 2017

16. Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex

Author: T. Dumontet, Antoine Martinez, Bruno Ragazzon, Anne-Marie Lefrançois-Martinez, Jean-Christophe Pointud, Nathanaëlle Montanier, Jérôme Bertherat, Igor Tauveron, Florence Roucher-Boulez, Isabelle Sahut-Barnola, Annabel Berthon, Damien Dufour, Pierre Val, Cyril Djari, M. Batisse-Lignier, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’endocrinologie diabétologie et maladies métaboliques, CHU Clermont-Ferrand, CHU Lyon, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d’Endocrinologie Diabète et Maladies Métaboliques [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Centre de référence des maladies rares de la surrénale ( CHU Cochin [AP-HP]), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), and Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, MESH: Neoplasm Proteins, MESH: Signal Transduction, MESH: beta Catenin, SUMO protein, MESH: Adrenal Cortex Neoplasms, Biochemistry, MESH: Mice, Knockout, Dexamethasone, MESH: Zona Fasciculata, Mice, 0302 clinical medicine, Cortex (anatomy), PKA, MESH: Animals, Cycloheximide, MESH: Cycloheximide, Wnt Signaling Pathway, beta Catenin, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Adrenal cortex, MESH: Sumoylation, MESH: Wnt Signaling Pathway, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, PIAS3.β-catenin, Cell biology, Neoplasm Proteins, medicine.anatomical_structure, MESH: Dexamethasone, Dactinomycin, Female, Zona Glomerulosa, Signal transduction, Biotechnology, Endocrine gland, Signal Transduction, MESH: Colforsin, MESH: Cell Line, Tumor, MESH: Mice, Transgenic, MESH: Zona Glomerulosa, MESH: Delayed-Action Preparations, Repressor, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Cyclic AMP-Dependent Protein Kinases, Biology, 03 medical and health sciences, MESH: Carney Complex, Adrenocorticotropic Hormone, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Animals, Humans, mouse models, Carney Complex, Molecular Biology, Psychological repression, MESH: Mice, MESH: Adrenocorticotropic Hormone, MESH: Humans, Colforsin, Sumoylation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, endocrine diseases, Cyclic AMP-Dependent Protein Kinases, Adrenal Cortex Neoplasms, MESH: Dactinomycin, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, SENP1/2, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Delayed-Action Preparations, MESH: Protein Processing, Post-Translational, Adrenal Cortex, MESH: Adrenal Cortex, Zona Fasciculata, Protein Processing, Post-Translational, MESH: Female, 030217 neurology & neurosurgery, Homeostasis
Abstract: SUMOylation is a highly conserved and dynamic post-translational mechanism primarily affecting nuclear programs for adapting organisms to stressful challenges. Alteration of SUMOylation cycles leads to severe developmental and homeostatic defects and malignancy, but signals coordinating SUMOylation are still unidentified. The adrenal cortex is a zonated endocrine gland that controls body homeostasis and stress response. Here, we show that in human and in mouse adrenals, SUMOylation follows a decreasing centripetal gradient that mirrors cortical differentiation flow and delimits highly and weakly SUMOylated steroidogenic compartments, overlapping glomerulosa, and fasciculata zones. Activation of PKA signaling by acute hormonal treatment, mouse genetic engineering, or in Carney complex results in repression of small ubiquitin-like modifier (SUMO) conjugation in the inner cortex by coordinating expression of SUMO pathway inducers and repressors. Conversely, genetic activation of canonical wingless-related integration site signaling maintains high SUMOylation potential in the outer neoplastic cortex. Thus, SUMOylation is tightly regulated by signaling pathways that orchestrate adrenal zonation and diseases.-Dumontet, T., Sahut-Barnola, I., Dufour, D., Lefrancois-Martinez, A.-M., Berthon, A., Montanier, N., Ragazzon, B., Djari, C., Pointud, J.-C., Roucher-Boulez, F., Batisse-Lignier, M., Tauveron, I., Bertherat, J., Val, P., Martinez, A. Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex.
Published: 2019

17. Stimulated thyroglobulin and thyroglobulin reduction index predict excellent response in differentiated thyroid cancers

Author: Gay-Bellile, Mathilde, DESSENNE, Pascal, LAQUET, Claire, Boussion, Véronique, Béguinot, Marie, PETIT, Marie-Françoise, Gremeau, Anne-Sophie, Verlet, Céline, Chaptal, Charlotte, Broult, Marilyn, Jouvency, Sylvie, Duclos, Martine, Bignon, Yves-Jean, Petit, Marie, Barres, Bertrand, KELLY, ANTONY, Kwiatkowski, Fabrice, Batisse-Lignier, Marie, Fouilhoux, Geneviève, Aubert, Bernadette, Dutheil, Frederic, Tauveron, Igor, Cachin, Florent, Maqdasy, Salwan, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service d'endocrinologie, diabétologie et maladies métaboliques [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service Santé Travail Environnement [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, WittyFit, Australian Catholic University (ACU), Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin, CRLCC Jean Perrin, Caisse Primaire Assurance Maladie (CAPM), Mollecular Oncology Laboratory, Laboratoire BDR CECOS - FIV AMP, CHU Estaing [Clermont-Ferrand], Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne, Unité de Nutrition Humaine (UNH), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Université de Poitiers, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Oncology, Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Biochemistry, Iodine Radioisotopes, 0302 clinical medicine, Endocrinology, Medicine, Lymph node, Thyroid cancer, Cancer, HBOC, Thyroid, Remission Induction, Middle Aged, Combined Modality Therapy, 3. Good health, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Predictive value of tests, Thyroidectomy, Female, Coping, Adult, Group sharing, medicine.medical_specialty, Thyroid Hormones, education, 030209 endocrinology & metabolism, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Oncogenetics, Psychodrama, Thyroglobulin, 03 medical and health sciences, Hope, Predictive Value of Tests, Internal medicine, Humans, Thyroid Neoplasms, differentiated thyroid cancer (DTC), Retrospective Studies, Radiofrequency Ablation, business.industry, Biochemistry (medical), Antineoplastic Protocols, Retrospective cohort study, medicine.disease, Young women, business
Abstract: Context Despite its good prognosis, differentiated thyroid cancer (DTC) is characterized by high rates of disease persistence and recurrence. Estimation of long-term remission (excellent response) thanks to specific parameters could help to individualize the active surveillance schedule. Objective Evaluation of the ability of stimulated thyroglobulin (Tg) and Tg reduction index (TRI) to predict long-term remission in patients with DTC managed by thyroidectomy and radioactive iodine (RAI) remnant ablation. Patients and Interventions Observational retrospective study of 1093 patients treated for DTC between 1995 and 2010. Preablation stimulated thyroglobulin (presTg) was measured under thyroid hormone withdrawal just before RAI. Recombinant human TSH–stimulated thyroglobulin (sTg) was measured at first evaluation of the initial management 6 to 12 months after RAI. TRI was calculated based on pre-Tg and sTg. Results After univariate and multivariate analyses, lymph node invasion (N1, OR = 2.08; 95% CI, 1.19 to 3.64), presTg (OR = 4.04; 95% CI, 2.56 to 6.38), sTg (OR = 2.62; 95% CI, 2.05 to 3.34), and TRI (OR = 0.43; 95% CI, 0.21 to 0.88) were identified as independent prognostic factors influencing the rate of disease persistence or recurrence after the initial management. Receiver operating characteristic analysis identified presTg cutoff (60% for the entire cohort and 62.5% for locally advanced disease (T3/T4, N1) was sensitive predictor for excellent response. Conclusion This study identifies presTg, sTg, and TRI as highly sensitive predictors of excellent response in patients with DTC and subsequently disease-free status. The cutoff of such parameters is also adapted for patients with higher tumor stages (T3/T4, N1).
Published: 2019

18. Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Author: Jules Audard, Loïc Blanchon, Christelle Gross, Vincent Sapin, Thomas Godet, Bertille Paquette, Matthieu Jabaudon, Justine Pasteur, Damien Bouvier, Raiko Blondonnet, Corinne Belville, Jean-Baptiste Joffredo, Marilyne Lavergne, Bruno Pereira, Jean-Michel Constantin, BLANCHON, LOIC, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, ARDS, Swine, Receptor for Advanced Glycation End Products, lcsh:Medicine, Pharmacology, Gastroenterology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, RAGE (receptor), Pathogenesis, 0302 clinical medicine, Interquartile range, Glycation, MESH: Animals, 050207 economics, Receptor, lcsh:Science, MESH: Swine, 0303 health sciences, Respiratory Distress Syndrome, 050208 finance, Multidisciplinary, 05 social sciences, respiratory system, 3. Good health, medicine.anatomical_structure, medicine.symptom, MESH: Oxygen, medicine.medical_specialty, MESH: Hemodynamics, Inflammation, Lung injury, Article, 03 medical and health sciences, Internal medicine, 0502 economics and business, medicine, Animals, 030304 developmental biology, Lung, business.industry, MESH: Receptor for Advanced Glycation End Products, lcsh:R, Antagonist, Hemodynamics, Oxygenation, Translational research, medicine.disease, Oxygen, Disease Models, Animal, 030104 developmental biology, 030228 respiratory system, Preclinical research, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Respiratory Distress Syndrome, Adult, lcsh:Q, MESH: Disease Models, Animal, business, 030217 neurology & neurosurgery
Abstract: BackgroundThe receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals.MethodsForty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (α1-ENaC), α1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h.FindingsTreatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8–21.7] and 19.5 [17.1–21.5] %/h, respectively, versus 12.6 [3.2–18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of α1-Na,K-ATPase and AQP-5.InterpretationRAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.FundingAuvergne Regional Council, Agence Nationale de la Recherche, Direction Générale de l’Offre de Soins.Research in ContextEvidence before this studyThe acute respiratory distress syndrome (ARDS), a clinical syndrome of diffuse pulmonary oedema and inflammation, currently lacks effective therapies and is associated with high mortality and morbidity. The degrees of lung epithelial injury and of alveolar fluid clearance (AFC) impairment, as evaluated by plasma levels of soluble receptor for glycation end-products (RAGE), are major prognostic factors in ARDS and potential therapeutic targets for ongoing research. For example, targeting RAGE with recombinant sRAGE or an anti-RAGE monoclonal antibody has proven beneficial in a translational mouse model of acid-induced ARDS.Added value of this studyIn a piglet model of acid-induced ARDS, treatment with RAGE antagonist peptide or recombinant sRAGE restored AFC and attenuated the features of lung injury, thereby confirming, in the closest evolutionary model species to humans, previous evidence from rodent models that modulation of RAGE may be a therapeutic option for ARDS. Although this is an important step towards future clinical translation, future studies should assess the best methods to modulate RAGE and further confirm the safety of manipulating this pathway in patients with ARDS.
Published: 2019

19. Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex

Author: T. Dumontet, Jean-Christophe Pointud, Anne-Marie Lefrançois-Martinez, Isabelle Sahut-Barnola, Cyril Djari, Igor Tauveron, Amandine Septier, Gwenneg Kerdivel, Christelle Damon-Soubeyrand, Coralie Drelon, Damien Richard, Annabel Berthon, Marie-Ange Calméjane, Pierre Val, Houda Tabbal, M. Batisse-Lignier, Antoine Martinez, Mickael Mathieu, Valentina Boeva, Stéphanie Rodriguez, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), CHU Gabriel Montpied (CHU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, endocrine system, Cellular differentiation, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, 03 medical and health sciences, 0302 clinical medicine, Zona fasciculata, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Adrenal insufficiency, Animals, Enhancer of Zeste Homolog 2 Protein, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Cyclic Nucleotide Phosphodiesterases, Type 7, Multidisciplinary, Adrenal cortex, Chemistry, EZH2, Cell Differentiation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cyclic Nucleotide Phosphodiesterases, Type 1, medicine.disease, Cyclic Nucleotide Phosphodiesterases, Type 3, Cell biology, Mice, Inbred C57BL, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, 030104 developmental biology, medicine.anatomical_structure, PNAS Plus, Zona glomerulosa, 030220 oncology & carcinogenesis, Histone methyltransferase, Pka signaling, Adrenal Cortex, Cyclic AMP-Dependent Protein Kinase RIbeta Subunit, Female, Steroids, Zona Glomerulosa, Zona Fasciculata, Homeostasis, Signal Transduction
Abstract: International audience; Adrenal cortex steroids are essential for body homeostasis, and adrenal insufficiency is a life-threatening condition. Adrenal endo-crine activity is maintained through recruitment of subcapsular progenitor cells that follow a unidirectional differentiation path from zona glomerulosa to zona fasciculata (zF). Here, we show that this unidirectionality is ensured by the histone methyltransferase EZH2. Indeed, we demonstrate that EZH2 maintains adrenal steroidogenic cell differentiation by preventing expression of GATA4 and WT1 that cause abnormal dedifferentiation to a progenitor-like state in Ezh2 KO adrenals. EZH2 further ensures normal cortical differentiation by programming cells for optimal response to adrenocorticotrophic hormone (ACTH)/PKA signaling. This is achieved by repression of phospho-diesterases PDE1B, 3A, and 7A and of PRKAR1B. Consequently, EZH2 ablation results in blunted zF differentiation and primary glucocorticoid insufficiency. These data demonstrate an all-encompassing role for EZH2 in programming steroidogenic cells for optimal response to differentiation signals and in maintaining their differentiated state. adrenal | differentiation | progenitors | PKA signaling | EZH2
Published: 2018

20. sRNAPipe: a Galaxy-based pipeline for bioinformatic in-depth exploration of small RNAseq data

Author: Pogorelcnik, Romain, Vaury, Chantal, Pouchin, Pierre, Jensen, Silke, Brasset, Emilie, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: lcsh:Genetics, Galaxy, lcsh:QH426-470, Pipeline, [SDV]Life Sciences [q-bio], sRNA-Seq, Small RNA sequencing, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Software, Bioinformatics analyses, ComputingMilieux_MISCELLANEOUS
Abstract: Background The field of small RNA is one of the most investigated research areas since they were shown to regulate transposable elements and gene expression and play essential roles in fundamental biological processes. Small RNA deep sequencing (sRNA-seq) is now routinely used for large-scale analyses of small RNA. Such high-throughput sequencing typically produces several millions reads. Results Here we present a computational pipeline (sRNAPipe: small RNA pipeline) based on the Galaxy framework that takes as input a fastq file of small RNA-seq reads and performs successive steps of mapping to categories of genomic sequences: transposable elements, gene transcripts, microRNAs, small nuclear RNAs, ribosomal RNAs and transfer RNAs. It also provides individual mapping and counting for chromosomes, transposable elements and gene transcripts, normalization, small RNA length analysis and plotting of the data along genomic coordinates to build publication-quality graphs and figures. sRNAPipe evaluates 10-nucleotide 5′-overlaps of reads on opposite strands to test ping-pong amplification for putative PIWI-interacting RNAs, providing counts of overlaps and corresponding z-scores. Conclusions sRNAPipe is easy to use and does not require command-line or coding knowledge. This pipeline gives quick visual and quantitative results, which are usable for publications. sRNAPipe is freely available as a Galaxy tool and via GitHub. Electronic supplementary material The online version of this article (10.1186/s13100-018-0130-7) contains supplementary material, which is available to authorized users.
Published: 2018

21. High-Affinity LNA-DNA Mixmer Probes for Detection of Chromosome-Specific Polymorphisms of 5S rDNA Repeats in Arabidopsis thaliana

Author: Lauriane, Simon, Aline V, Probst, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: LNA–DNA mixmer probes, Arabidopsis thaliana, Fluorescence in situ hybridization, [SDV]Life Sciences [q-bio], Arabidopsis, RNA, Ribosomal, 5S, 5S rDNA, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, DNA, Ribosomal, Polymorphism, Single Nucleotide, Chromosomes, Plant, Binding affinity, Nuclei spreads, DNA Probes, In Situ Hybridization, Fluorescence, Repetitive Sequences, Nucleic Acid
Abstract: International audience; Fluorescence in situ hybridization is a standard technique to visualize specific DNA sequences by hybridization with fluorescent probes and, most commonly, relies on DNA probes generated by nick translation. In this chapter, we describe the use of directly labeled LNA-DNA mixmer probes for the rapid detection of repetitive sequences on Arabidopsis thaliana nuclei spreads. We further demonstrate that due to the high thermal stability of the heteroduplexes and the resulting elevated binding affinity of LNA-DNA mixmer probes for their target DNA, these probes can be used to discriminate between repetitive sequences differing by only a few single nucleotide polymorphisms.
Published: 2018

22. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients

Author: Vincent Sapin, Damien Bouvier, Jeannot Schmidt, Daniel Pic, Jean Roubin, Farès Moustafa, Gautier Allouchery, Bruno Pereira, Julien Raconnat, Département des Urgences, CHU Clermont-Ferrand, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Laboratoire de Biochimie, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), service de Biostatistiques, DRCI, Centre Hospitalier Universitaire de Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: genetic structures, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clinical Biochemistry, S100B, Cohort Studies, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Medicine, Prospective Studies, Prospective cohort study, MESH: Cohort Studies, MESH: Aged, MESH: Middle Aged, Age Factors, Retrograde amnesia, General Medicine, Middle Aged, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Platelet Aggregation Inhibitors, MESH: Young Adult, Cohort, Medium Risk, Adult, medicine.medical_specialty, Adolescent, Alcohol Drinking, Traumatic brain injury, S100 Calcium Binding Protein beta Subunit, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, mTBI, Internal medicine, mild traumatic brain injury, Humans, In patient, Aged, MESH: Adolescent, MESH: Age Factors, MESH: Humans, Adult patients, business.industry, MESH: S100 Calcium Binding Protein beta Subunit, Biochemistry (medical), Significant difference, 030208 emergency & critical care medicine, MESH: Adult, medicine.disease, eye diseases, MESH: Prospective Studies, MESH: Sensitivity and Specificity, Brain Injuries, MESH: Brain Injuries, MESH: Biomarkers, sense organs, business, 030217 neurology & neurosurgery, Biomarkers, Platelet Aggregation Inhibitors, MESH: Alcohol Drinking
Abstract: Background: This study’s primary objective was to validate the routine use of S100B via a prospective study. The aim was a reduction of cranial computed tomography (CCT) scans by 30%. The secondary goal was to investigate the influence of age and associated risk factors on the reduction of CCT. Methods: S100B (sampling within 3 h postinjury) was used for patients with mild traumatic brain injury (mTBIs) presenting a medium risk of complications and requiring a CCT scan. Patients with negative S100B (S100B−) were discharged without a CCT scan. Results: Of the 1449 patients included in this study, 468 (32.3%) had S100B− with a sensitivity of 96.4% (95% CI: 87.5%–99.6%), a specificity of 33.4% (95% CI: 31%–36%) and a negative predictive value of 99.6% (95% CI: 98.5%–99.9%). No significant difference in serum levels or the S100B+ rate was observed if patients had retrograde amnesia (0.16 μg/L; 63.8%), loss of consciousness (0.13; 63.6%) or antiplatelet therapy (0.20; 77.9%). Significant differences were found between the S100B concentrations and S100B positivity rates in patients >65 years old and all the groups with patients 65 years old (n=504). Conclusions: The clinical use of S100B in mTBI management reduces the use of CCTs by approximately one-third; furthermore, the percentage of CCTs reduction is influenced by the age of the patient.
Published: 2018

23. Driving pressure and acute respiratory distress syndrome in critically ill patients

Author: Blondonnet, Raiko, Joubert, Elodie, Godet, Thomas, Berthelin, Pauline, Pranal, Thibaut, Roszyk, Laurence, Chabanne, Russell, Eisenmann, Nathanael, Lautrette, Alexandre, Belville, Corinne, Cayot, Sophie, Gillart, Thierry, Souweine, Bertrand, Bouvier, Damien, Blanchon, Loïc, Sapin, Vincent, Pereira, Bruno, Constantin, Jean-Michel, Jabaudon, Matthieu, Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Biochimie, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Correlation of Data, MESH: Humans, MESH: Middle Aged, MESH: Adult, acute respiratory distress syndrome, driving pressure, mechanical ventilation, intensive care unit, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Male, risk prediction, MESH: Positive-Pressure Respiration, MESH: Critical Care, MESH: Risk Factors, MESH: Critical Illness, MESH: Respiratory Distress Syndrome, Adult, MESH: Intensive Care Units, MESH: Respiration, Artificial, MESH: Female, MESH: Risk Adjustment
Abstract: International audience; Elevated driving pressure (ΔP) may be associated with increased risk of acute respiratory distress syndrome (ARDS) in patients admitted via the emergency department and with post-operative pulmonary complications in surgical patients. This study investigated the association of higher ΔP with the onset of ARDS in a high-risk, intensive care unit (ICU) population.
Published: 2018

24. CBP and P300 regulate distinct gene networks required for human primary myoblast differentiation and muscle integrity

Author: Fauquier, Lucas, Azzag, Karim, Mendoza Parra, Marco Antonio, Quillien, Aurélie, Boulet, Manon, Diouf, Sarah, Carnac, Gilles, Waltzer, Lucas, Gronemeyer, Hinrich, Vandel, Laurence, Centre de biologie du développement (CBD), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-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 de Strasbourg (UNISTRA), MENDOZA PARRA, Marco Antonio, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI)
Subjects: Transcriptional Activation, Transcription, Genetic, Sialoglycoproteins, [SDV]Life Sciences [q-bio], Primary Cell Culture, lcsh:Medicine, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Muscle Development, Article, Cell Line, Myoblasts, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, Humans, Gene Regulatory Networks, lcsh:Science, Muscle, Skeletal, Promoter Regions, Genetic, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Zebrafish, ComputingMilieux_MISCELLANEOUS, lcsh:R, Cell Differentiation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Peptide Fragments, Trans-Activators, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, E1A-Associated p300 Protein
Abstract: International audience; The acetyltransferases CBP and P300 have been implicated in myogenesis in mouse immortalized cell lines but these studies focused only on the expression of a handful of myogenic factors. Hence, the respective role of these two related cofactors and their impact at global scale on gene expression rewiring during primary myoblast differentiation remain unknown. Here, we characterised the gene networks regulated by these two epigenetic enzymes during human primary myoblast differentiation (HPM). We found that CBP and p300 play a critical role in the activation of the myogenic program and mostly regulate distinct gene sets to control several aspects of HPM biology, even though they also exhibit some degree of redundancy. Moreover, CBP or P300 knockdown strongly impaired muscle cell adhesion and resulted in the activation of inflammation markers, two hallmarks of dystrophic disease. This was further validated in zebrafish where inhibition of CBP and P300 enzymatic activities led to cell adhesion defects and muscle fiber detachment. Our data highlight an unforeseen link between CBP/ P300 activity and the emergence of dystrophic phenotypes. They thereby identify CBP and P300 as mediators of adult muscle integrity and suggest a new lead for intervention in muscular dystrophy.
Published: 2018

25. Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse

Author: El Khouri, Elma, Whitfield, Marjorie, Stouvenel, Laurence, Kini, Archana, Riederer, Brigitte, Lorès, Patrick, Roemermann, Dorothee, di Stefano, Gabriella, Drevet, Joël, Saez, Fabrice, Seidler, Ursula, Touré, Aminata, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Gastroenterology, Hepatology and Endocrinology (MHH), Hannover Medical School [Hannover] (MHH), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

26. Replication-coupled histone H3.1 deposition determines nucleosome composition and heterochromatin dynamics during Arabidopsis seedling development

Author: Céline Duc, Sophie Desset, Samuel Le Goff, Aline V. Probst, Sylviane Cotterell, Matthias Benoit, Lauriane Simon, Axel Poulet, Christophe Tatout, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: DNA Replication, 0106 biological sciences, 0301 basic medicine, Physiology, Heterochromatin, [SDV]Life Sciences [q-bio], Arabidopsis, Plant Science, Biology, 01 natural sciences, Histones, 03 medical and health sciences, Histone H3, Histone H1, Nucleosome, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Chromatin Assembly Factor-1, ComputingMilieux_MISCELLANEOUS, Repetitive Sequences, Nucleic Acid, CAF-1, Arabidopsis Proteins, Lysine, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Chromatin Assembly and Disassembly, Plants, Genetically Modified, Nucleosomes, Chromatin, Cell biology, 030104 developmental biology, Histone, Seedlings, Mutation, biology.protein, RNA Splicing Factors, 010606 plant biology & botany
Abstract: Developmental phase transitions are often characterized by changes in the chromatin landscape and heterochromatin reorganization. In Arabidopsis, clustering of repetitive heterochromatic loci into so-called chromocenters is an important determinant of chromosome organization in nuclear space. Here, we investigated the molecular mechanisms involved in chromocenter formation during the switch from a heterotrophic to a photosynthetically competent state during early seedling development. We characterized the spatial organization and chromatin features at centromeric and pericentromeric repeats and identified mutant contexts with impaired chromocenter formation. We find that clustering of repetitive DNA loci into chromocenters takes place in a precise temporal window and results in reinforced transcriptional repression. Although repetitive sequences are enriched in H3K9me2 and linker histone H1 before repeat clustering, chromocenter formation involves increasing enrichment in H3.1 as well as H2A.W histone variants, hallmarks of heterochromatin. These processes are severely affected in mutants impaired in replication-coupled histone assembly mediated by CHROMATIN ASSEMBLY FACTOR 1 (CAF-1). We further reveal that histone deposition by CAF-1 is required for efficient H3K9me2 enrichment at repetitive sequences during chromocenter formation. Taken together, we show that chromocenter assembly during post-germination development requires dynamic changes in nucleosome composition and histone post-translational modifications orchestrated by the replication-coupled H3.1 deposition machinery.
Published: 2018

27. The Biomarker S100B and Mild Traumatic Brain Injury: A Meta-analysis

Author: Bruno Pereira, Charlotte Oris, Vincent Sapin, Damien Bouvier, Sergio Manzano, Christoph Castellani, Julie Durif, Jeanne Simon-Pimmel, service de Biostatistiques, DRCI, CHU Clermont-Ferrand, Pediatric Emergency Division [Geneva], Geneva University Hospital (HUG), Laboratoire de Biochimie, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Délégation à la recherche clinique et aux innovations (DRCI), CHU de Clermont-Ferrand, Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Time Factors, Traumatic brain injury, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MEDLINE, Context (language use), S100 Calcium Binding Protein beta Subunit, 030204 cardiovascular system & hematology, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, S100 Calcium Binding Protein beta Subunit/blood, Reference Values, Internal medicine, MESH: Child, Medicine, Humans, Sampling (medicine), [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Child, Tomography, Brain Concussion, ddc:618, MESH: Humans, MESH: Brain Concussion, business.industry, MESH: S100 Calcium Binding Protein beta Subunit, MESH: Time Factors, MESH: Reference Values, medicine.disease, Confidence interval, MESH: Sensitivity and Specificity, 3. Good health, X-Ray Computed, Data extraction, Meta-analysis, Pediatrics, Perinatology and Child Health, MESH: Biomarkers, Biomarker (medicine), Brain Concussion/blood/diagnosis/diagnostic imaging/etiology, business, Tomography, X-Ray Computed, MESH: Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Biomarkers, Biomarkers/blood
Abstract: CONTEXT: The usefulness of S100B has been noted as a biomarker in the management of mild traumatic brain injury (mTBI) in adults. However, S100B efficacy as a biomarker in children has previously been relatively unclear. OBJECTIVE: A meta-analysis is conducted to assess the prognostic value of S100B in predicting intracerebral lesions in children after mTBI. DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and Google Scholar. STUDY SELECTION: Studies including children suffering mTBI who underwent S100B measurement and computed tomography (CT) scans were included. DATA EXTRACTION: Of 1030 articles screened, 8 studies met the inclusion criteria. RESULTS: The overall pooled sensitivity and specificity were 100% (95% confidence interval [CI]: 98%–100%) and 34% (95% CI: 30%–38%), respectively. A second analysis was based on the collection of 373 individual data points from 4 studies. Sensitivity and specificity results, obtained from reference ranges in children with a sampling time LIMITATIONS: Only patients undergoing both a CT scan and S100B testing were selected for evaluation. CONCLUSIONS: S100B serum analysis as a part of the clinical routine could significantly reduce the number of CT scans performed on children with mTBI. Sampling should take place within 3 hours of trauma. Cutoff levels should be based on pediatric reference ranges.
Published: 2018

28. Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine Amnion

Author: Debra F. Anderson, Loïc Blanchon, Marion Rouzaire, Cecilia Y. Cheung, Robert A. Brace, Vincent Sapin, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Biochimie, CHU Clermont-Ferrand, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Vascular Endothelial Growth Factor A, 0301 basic medicine, Receptors, Retinoic Acid, medicine.drug_class, Retinoic acid, Tretinoin, RAR and RXR, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Andrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Pregnancy, Placenta, sheep fetal membranes, medicine, Animals, Amnion, Retinoid, Receptor, Cells, Cultured, reproductive and urinary physiology, Messenger RNA, Sheep, 030219 obstetrics & reproductive medicine, Chemistry, Obstetrics and Gynecology, amniotic fluid, intramembranous transport, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Original Articles, Vascular endothelial growth factor, 030104 developmental biology, medicine.anatomical_structure, embryonic structures, Female, tissues, Signal Transduction
Abstract: International audience; Vascular endothelial growth factor (VEGF) has been proposed as an important regulator of amniotic fluid absorption across the amnion into the fetal vasculature on the surface of the placenta. However, the activators of VEGF expression and action in the amnion have not been identified. Using the pregnant sheep model, we aimed to investigate the presence of the retinoic acid (RA) pathway in ovine amnion and to determine its effect on VEGF expression. Further, we explored relationships between RA receptors and VEGF and tested the hypothesis that RA modulates intramembranous absorption (IMA) through induction of amnion VEGF in sheep fetuses subjected to altered IMA rates. Our study showed that RA receptor isoforms were expressed in sheep amnion, and RA response elements (RAREs) were identified in ovine RARβ and VEGF gene promoters. In ovine amnion cells, RA treatment upregulated RARβ messenger RNA (mRNA) and increased VEGF transcript levels. In sheep fetuses, increases in IMA rate was associated with elevated VEGF mRNA levels in the amnion but not in the chorion. Further, RARβ mRNA was positively correlated with VEGF mRNA levels in the amnion and not chorion. We conclude that an RA pathway is present in ovine fetal membranes and that RA is capable of inducing VEGF. The finding of a positive relationship between amnion VEGF and RARβ during altered IMA rate suggests that the retinoid pathway may play a role through VEGF in regulating intramembranous transport across the amnion.
Published: 2018

29. Jak-Stat pathway induces Drosophila follicle elongation by a gradient of apical contractility

Author: Vincent Mirouse, Olivier Bardot, Hervé Alégot, Pierre Pouchin, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Génétique, Reproduction et Développement - Clermont Auvergne ( GReD ), Institut National de la Santé et de la Recherche Médicale-Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), This work was funded by the ATIP-Avenir program, Association pour la Recherche contre le Cancer (ARC) and the Auvergne Region., Mirouse, vincent, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: [SDV.BA] Life Sciences [q-bio]/Animal biology, QH301-705.5, Science, morphogenesis, Matrix (biology), [ SDV.BDD.MOR ] Life Sciences [q-bio]/Development Biology/Morphogenesis, developmental biology, 03 medical and health sciences, 0302 clinical medicine, Ovarian Follicle, stem cells, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Cell polarity, Myosin, medicine, Animals, Drosophila Proteins, Biology (General), Cytoskeleton, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Janus Kinases, 030304 developmental biology, 0303 health sciences, D. melanogaster, Chemistry, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, Apical constriction, dynamics, morphogen, Epithelium, [SDV.BDD.MOR] Life Sciences [q-bio]/Development Biology/Morphogenesis, Cell biology, STAT Transcription Factors, Developmental Biology and Stem Cells, medicine.anatomical_structure, Medicine, Drosophila, Female, Elongation, 030217 neurology & neurosurgery, Research Article, Signal Transduction, Transcription Factors, Morphogen
Abstract: Tissue elongation and its control by spatiotemporal signals is a major developmental question. Currently, it is thought thatDrosophilaovarian follicular epithelium elongation requires the planar polarization of the basal domain cytoskeleton and of the extra-cellular matrix, associated with a dynamic process of rotation around the anteroposterior axis. Here we show, by careful kinetic analysis offat2mutants, that neither basal planar polarization nor rotation is required during a first phase of follicle elongation. Conversely, a JAK-STAT signaling gradient from each follicle pole orients early elongation. JAK-STAT controls apical pulsatile contractions, and Myosin II activity inhibition affects both pulses and early elongation. Early elongation is associated with apical constriction at the poles and oriented cell rearrangements, but without any visible planar cell polarization of the apical domain. Thus, a morphogen gradient can trigger tissue elongation via a control of cell pulsing and without planar cell polarity requirement.Impact StatementFollicle elongation does not rely solely on the basal side of the cells but also requires a mechanism integrating a developmental cue with a morphogenetic process involving their apical domain.
Published: 2018

30. High frequency percussive ventilation increases alveolar recruitment in early acute respiratory distress syndrome: an experimental, physiological and CT scan study

Author: Thomas Godet, Emmanuel Futier, Matthieu Jabaudon, Bruno Pereira, Raiko Blondonnet, Jean-Michel Constantin, Jules Audard, Benjamin Rieu, J M Garcier, Aymeric Tremblay, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Université de Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and BLANCHON, LOIC
Subjects: ARDS, MESH: Pulmonary Alveoli, medicine.medical_treatment, Hemodynamics, Hyperinflation, Critical Care and Intensive Care Medicine, MESH: Tidal Volume, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Mechanical ventilation, Medicine, Lung volumes, MESH: Animals, 030212 general & internal medicine, MESH: Swine, MESH: Aged, Respiratory Distress Syndrome, MESH: Statistics, Nonparametric, MESH: Middle Aged, Acute respiratory distress syndrome, lcsh:Medical emergencies. Critical care. Intensive care. First aid, respiratory system, medicine.anatomical_structure, Lung morphology, Breathing, Cardiology, MESH: Tomography, X-Ray Computed, medicine.medical_specialty, Alveolar recruitment, MESH: Arterial Pressure, MESH: Blood Gas Analysis, High-Frequency Ventilation, 03 medical and health sciences, Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, MESH: Lung, MESH: High-Frequency Ventilation, Lung, MESH: Humans, business.industry, Research, 030208 emergency & critical care medicine, Oxygenation, lcsh:RC86-88.9, medicine.disease, Respiration, Artificial, Alveolar hyperinflation, MESH: Male, MESH: Prospective Studies, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Respiratory Distress Syndrome, Adult, High frequency percussive ventilation, MESH: Disease Models, Animal, business, MESH: Female
Abstract: Background High frequency percussive ventilation (HFPV) combines diffusive (high frequency mini-bursts) and convective ventilation patterns. Benefits include enhanced oxygenation and hemodynamics, and alveolar recruitment, while providing hypothetic lung-protective ventilation. No study has investigated HFPV-induced changes in lung aeration in patients with early acute respiratory distress syndrome (ARDS). Methods Eight patients with early non-focal ARDS were enrolled and five swine with early non-focal ARDS were studied in prospective computed tomography (CT) scan and animal studies, in a university-hospital tertiary ICU and an animal laboratory. Patients were optimized under conventional “open-lung” ventilation. Lung CT was performed using an end-expiratory hold (Conv) to assess lung morphology. HFPV was applied for 1 hour to all patients before new CT scans were performed with end-expiratory (HFPV EE) and end-inspiratory (HFPV EI) holds. Lung volumes were determined after software analysis. At specified time points, blood gases and hemodynamic data were collected. Recruitment was defined as a change in non-aerated lung volumes between Conv, HFPV EE and HFPV EI. The main objective was to verify whether HFPV increases alveolar recruitment without lung hyperinflation. Correlation between pleural, upper airways and HFPV-derived pressures was assessed in an ARDS swine-based model. Results One-hour HFPV significantly improved oxygenation and hemodynamics. Lung recruitment significantly rose by 12.0% (8.5–18.0%), P = 0.05 (Conv-HFPV EE) and 12.5% (9.3–16.8%), P = 0.003 (Conv-HFPV EI). Hyperinflation tended to increase by 2.0% (0.5–2.5%), P = 0.89 (Conv-HFPV EE) and 3.0% (2.5–4.0%), P = 0.27 (Conv-HFPV EI). HFPV hyperinflation correlated with hyperinflated and normally-aerated lung volumes at baseline: r = 0.79, P = 0.05 and r = 0.79, P = 0.05, respectively (Conv-HFPV EE); and only hyperinflated lung volumes at baseline: r = 0.88, P = 0.01 (Conv-HFPV EI). HFPV CT-determined tidal volumes reached 5.7 (1.1–8.1) mL.kg-1 of ideal body weight (IBW). Correlations between pleural and HFPV-monitored pressures were acceptable and end-inspiratory pleural pressures remained below 25cmH20. Conclusions HFPV improves alveolar recruitment, gas exchanges and hemodynamics of patients with early non-focal ARDS without relevant hyperinflation. HFPV-derived pressures correlate with corresponding pleural or upper airways pressures. Trial registration ClinicalTrials.gov, NCT02510105. Registered on 1 June 2015. The trial was retrospectively registered. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1924-6) contains supplementary material, which is available to authorized users.
Published: 2018

31. Investigation of Nuclear Periphery Protein Interactions in Plants Using the Membrane Yeast Two-Hybrid (MbY2H) System

Author: Voisin, Maxime, Vanrobays, Emmanuel, Tatout, Christophe, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cell Nucleus, Interactome, Arabidopsis thaliana, Genetic Vectors, Gene Expression, Membrane Proteins, Nuclear Proteins, Yeast two-hybrid, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, Plant Cells, Two-Hybrid System Techniques, Membrane protein, Protein Interaction Mapping, LINC complex, Cloning, Molecular, Gene Library, Protein Binding
Abstract: International audience; Identification of membrane protein interactomes is a key issue to better understand how these molecules carry out their functions. However, protein-protein interactions using conventional interaction assays are particularly challenging for integral membrane proteins, because of their hydrophobic nature. Here we describe the membrane yeast two-hybrid (MbY2H) system, a powerful tool for identifying the interactors of membrane and membrane-associated proteins.
Published: 2018

32. Reply to Riché et al.: Sevoflurane in Acute Respiratory Distress Syndrome: Are Lung Protection and Anesthesia Depth Influenced by Pulmonary Morphology?

Author: Matthieu Jabaudon, Raiko Blondonnet, Jean-Michel Constantin, Thomas Godet, Emmanuel Futier, Jean-Etienne Bazin, Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Service de Médecine Intensive et Réanimation [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Pulmonary and Respiratory Medicine, Pilot Projects, Acute respiratory distress, Critical Care and Intensive Care Medicine, MESH: Anesthesia, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Sevoflurane, 03 medical and health sciences, 0302 clinical medicine, MESH: Sevoflurane, medicine, Humans, MESH: Lung, Anesthesia, Lung, ComputingMilieux_MISCELLANEOUS, Respiratory Distress Syndrome, MESH: Humans, Lung protection, business.industry, 030208 emergency & critical care medicine, MESH: Pilot Projects, 3. Good health, 030228 respiratory system, MESH: Respiratory Distress Syndrome, Adult, business, medicine.drug
Abstract: International audience
Published: 2017

33. OXIDATIVE STRESS AND MITOCHONDRIAL DYNAMICS MALFUNCTION ARE LINKED IN PELIZAEUS-MERZBACHER DISEASE

Author: Odile Boespflug-Tanguy, Marie-Noëlle Bonnet-Dupeyron, Mélina Bégou, Johan Auwerx, Jone López-Erauskin, Aurora Pujol, Nathalie Launay, Céline Guéret-Gonthier, Catherine Vaurs-Barrière, Pablo Ranea-Robles, Patrizia Bianchi, Stéphane Fourcade, Bérengère Petit, Laia Morató, Montserrat Ruiz, Cristina Guilera, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pharmacologie fondamentale et clinique de la douleur, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratory of Integrative and Systems Physiology (LISP), Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuro-Dol - Clermont Auvergne (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Dol - Clermont Auvergne ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Neuro-Dol ( Neuro-Dol ), Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Génétique, reproduction et développement ( GReD ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR79-Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), Laboratory of Integrative and Systems Physiology ( LISP ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, 0301 basic medicine, Proteolipid protein 1, Pelizaeus-Merzbacher Disease, [SDV]Life Sciences [q-bio], experimental autoimmune encephalomyelitis, Mitochondrion, medicine.disease_cause, Mitochondrial Dynamics, Pelizaeus‐Merzbacher disease, Myelin, 0302 clinical medicine, oxidative stress, alzheimers-disease, Child, Cells, Cultured, Research Articles, ComputingMilieux_MISCELLANEOUS, General Neuroscience, Neurodegeneration, Mitochondria, Rare diseases, 3. Good health, Myelin proteolipid protein, Cell biology, antioxidants, medicine.anatomical_structure, Spinal Cord, multiple-sclerosis, Child, Preschool, Malalties rares, axonal degeneration, Research Article, Estrès oxidatiu, Glutamic Acid, Mice, Transgenic, Oxidative phosphorylation, Biology, DNA, Mitochondrial, energy-metabolism, Pathology and Forensic Medicine, Mitochondrial Proteins, 03 medical and health sciences, medicine, Animals, Humans, RNA, Messenger, Myelin Proteolipid Protein, [ SDV ] Life Sciences [q-bio], bioenergetic failure, Infant, Pelizaeus–Merzbacher disease, proteomic identification, Fibroblasts, medicine.disease, Mice, Inbred C57BL, transgenic mouse model, 030104 developmental biology, Oxidative stress, central-nervous-system, x-adrenoleukodystrophy, Neurology (clinical), 030217 neurology & neurosurgery
Abstract: Pelizaeus‐Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. The Plp1 overexpressing mouse model (PLP‐tg66/66) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan. The sequence of cellular events that cause neurodegeneration and ultimately death is poorly understood. In this work, we analyzed patient‐derived fibroblasts and spinal cords of the PLP‐tg66/66 mouse model, and identified redox imbalance, with altered antioxidant defense and oxidative damage to several enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We also evidenced malfunction of the mitochondria compartment with increased ROS production and depolarization in PMD patient's fibroblasts, which was prevented by the antioxidant N‐acetyl‐cysteine. Finally, we uncovered an impairment of mitochondrial dynamics in patient's fibroblasts which may help explain the ultrastructural abnormalities of mitochondria morphology detected in spinal cords from PLP‐tg66/66 mice. Altogether, these results underscore the link between redox and metabolic homeostasis in myelin diseases, provide insight into the pathophysiology of PMD, and may bear implications for tailored pharmacological intervention.
Published: 2017

34. Biological properties of propolis extracts: Something new from an ancient product

Author: Allan Fouache, Amar Zellagui, Amalia Trousson, Silvère Baron, Mesbah Lahouel, Jean-Marc A. Lobaccaro, Nada Zabaiou, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Antifungal, Antifungal Agents, medicine.drug_class, Anti-Inflammatory Agents, Cancer therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ethanolic extracts, Biology, Biochemistry, Propolis, Terpene, 03 medical and health sciences, Honey Bees, P70S6 kinase, Neoplasms, Biological property, Botany, medicine, Animals, Humans, Molecular Biology, Prostate cancer, Cell Proliferation, Traditional therapy, Plant Extracts, Organic Chemistry, Flavonoids, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Antineoplastic Agents, Phytogenic, Anti-Bacterial Agents, 3. Good health, 030104 developmental biology, Ethnobotany
Abstract: International audience; Natural products are an interesting source of new therapeutics, especially for cancer therapy as 70% of them have botany origin. Propolis, a resinous mixture that honey bees collect and transform from tree buds, sap flows, or other botanical sources, has been used by ethnobotany and traditional practitioners as early in Egypt as 3000 BCE. Enriched in flavonoids, phenol acids and terpene derivatives, propolis has been widely used for its antibacterial, antifungal and anti-inflammatory properties. Even though it is a challenge to standardize propolis composition, chemical analyses have pointed out interesting molecules that also present anti-oxidant and anti-proliferative properties that are of interest in the field of anti-cancer therapy. This review describes the various geographical origins and compositions of propolis, and analyzes how the main compounds of propolis could modulate cell signaling. A focus is made on the putative use of propolis in prostate cancer.
Published: 2017

35. Effect of hibernating bear serum effect on human myotubes transcriptome: BMP signaling regulation

Author: Richard, Chloé, Fourneaux, Guillaume, Geffroy, Alexandre, Coudy-Gandilhon, Cécile, Cueff, Gwendal, Tatout, Christophe, Gauquelin-Koch, Guillemette, Lefai, Etienne, Bertile, Fabrice, Combaret, Lydie, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut Pluridisciplinaire Hubert Curien (IPHC), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre National d’Études Spatiales [Paris] (CNES), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Abstract: International audience; Muscle loss (atrophy) is observed in several physio-pathological situations and has very harmful consequences for the patients. However, despite a thorough understanding of muscle atrophy mechanisms using rodent and human models, no effective treatment is yet available. We use a bioinspired approach from the brown bear, which is naturally resistant to muscle atrophy during winter hibernation. We previously reported that this phenotype was associated with the maintenance or activation of the BMP (Bone Morphogenetic Protein) pathway (1), which positively controls muscle mass. We have also shown that winter bear serum (WBS) displays translational effects on human myotubes by inducing hypertrophy (2). Here, we aimed at further investigating the effect of WBS on human myotubes using large-scale transcriptomic analysis (mRNA sequencing) complemented using Western-blots. We identified 24,826 genes, of which 352 were differentially expressed between human myotubes cultivated for 48h with 5% of WBS or summer bear serum (SBS). Functional annotation analysis using the Gene Ontology resource revealed significant enrichment of biological processes related to (i) muscle function, (ii) extracellular matrix remodeling and (iii) negative regulation of BMP signaling. More precisely, we observed that several BMP signaling endogenous inhibitors were down-regulated at the mRNA and protein levels. Overall, these data show that hibernating bear serum induces transcriptomic reprogramming of BMP signaling regulation in human myotubes. Furthermore, the down-regulation of BMP inhibitors suggests a reduction in the repressive processes of the BMP pathway. Further studies will investigate how this reprogramming might influence BMP signaling and/or muscle mass maintenance under catabolic conditions.
Published: 2023

36. Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression

Author: Gwénaëlle Détourné, Axel Poulet, Christophe Tatout, Alaguraj Veluchamy, Lauriane Simon, Sylviane Cotterell, Matthias Benoit, David Latrasse, Moussa Benhamed, Matthieu Jung, Samuel Le Goff, Céline Duc, Aline V. Probst, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), 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), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Recherche Agronomique (INRA), ANR [ANR-10-INBS-0009], Region Auvergne, ANR [ANR-11 JSV2 009 01, ANR-12 ISV6 0001], CNRS, INSERM, Universite Clermont Auvergne, and 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)
Subjects: 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, X-linked Nuclear Protein, Hydrolases, Arabidopsis, Plant Science, DNA, Ribosomal, Histones, 03 medical and health sciences, Histone H3, Gene Expression Regulation, Plant, hemic and lymphatic diseases, Histone H2A, Nucleosome, Histone code, ATRX, Research Articles, Phylogeny, Genetics, biology, Arabidopsis Proteins, Epistasis, Genetic, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Plants, Genetically Modified, Chromatin, 030104 developmental biology, Histone, Chaperone (protein), Mutation, biology.protein, Molecular Chaperones
Abstract: International audience; Histones are essential components of the nucleosome, the major chromatin subunit that structures linear DNA molecules and regulates access of other proteins to DNA. Specific histone chaperone complexes control the correct deposition of canonical histones and their variants to modulate nucleosome structure and stability. In this study, we characterize the Arabidopsis thaliana Alpha Thalassemia-mental Retardation X-linked (ATRX) ortholog and show that ATRX is involved in histone H3 deposition. Arabidopsis ATRX mutant alleles are viable, but show developmental defects and reduced fertility. Their combination with mutants of the histone H3.3 chaperone HIRA (Histone Regulator A) results in impaired plant survival, suggesting that HIRA and ATRX function in complementary histone deposition pathways. Indeed, ATRX loss of function alters cellular histone H3.3 pools and in consequence modulates the H3.1/H3.3 balance in the cell. H3.3 levels are affected especially at genes characterized by elevated H3.3 occupancy, including the 45S ribosomal DNA (45S rDNA) loci, where loss of ATRX results in altered expression of specific 45S rDNA sequence variants. At the genome-wide scale, our data indicate that ATRX modifies gene expression concomitantly to H3.3 deposition at a set of genes characterized both by elevated H3.3 occupancy and high expression. Together, our results show that ATRX is involved in H3.3 deposition and emphasize the role of histone chaperones in adjusting genome expression.
Published: 2017

37. Retinoic Acid Engineered Amniotic Membrane Used as Graft or Homogenate: Positive Effects on Corneal Alkali Burns

Author: Vincent Sapin, Christelle Gross, Loïc Blanchon, Aurélie Comptour, R. Joubert, E Daniel, N. Bonnin, Frédéric Chiambaretta, Corinne Belville, Recherches Avicoles (SRA), Institut National de la Recherche Agronomique (INRA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Laboratoire de Biochimie, Centre Hospitalier Universitaire de Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Gabriel Montpied [Clermont-Ferrand], Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, medicine.medical_specialty, Retinoic acid, Transplants, Tretinoin, Alkalies, Pharmacology, Mice, 03 medical and health sciences, chemistry.chemical_compound, Corneal Burn, Keratolytic Agents, 0302 clinical medicine, Cornea, Burns, Chemical, medicine, Animals, Humans, Amnion, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Corneal Ulcer, Fluorescent Antibody Technique, Indirect, Wound Healing, Tissue Engineering, business.industry, 3. Good health, Surgery, Vascular endothelial growth factor, Disease Models, Animal, Eye Burns, Retinoic acid receptor, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, chemistry, 030221 ophthalmology & optometry, business, Wound healing, medicine.drug
Abstract: Purpose Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment. Methods Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified. Results AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins. Conclusions Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.
Published: 2017

38. Myocilin expression is regulated by retinoic acid in the trabecular meshwork-derived cellular environment

Author: Vincent Sapin, Geoffroy Marceau, Aurélie Comptour, Frédéric Chiambaretta, C. Prat, Loïc Blanchon, Gael Clairefond, Corinne Belville, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laoratoire de Biochimie, CHU Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], Laboratoire de Biochimie, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, genetic structures, Retinoic acid, Glaucoma, chemistry.chemical_compound, 0302 clinical medicine, Trabecular meshwork, Cells, Cultured, Regulation of gene expression, Immunohistochemistry, Sensory Systems, Cell biology, medicine.anatomical_structure, Glaucoma, Open-Angle, medicine.drug, medicine.medical_specialty, Open angle glaucoma, Blotting, Western, Tretinoin, Biology, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, Cellular and Molecular Neuroscience, Retinoids, Keratolytic Agents, Internal medicine, medicine, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Eye Proteins, Myocilin, Intraocular Pressure, Glycoproteins, medicine.disease, eye diseases, Gene regulation, Ophthalmology, Cytoskeletal Proteins, 030104 developmental biology, Endocrinology, chemistry, Gene Expression Regulation, 030221 ophthalmology & optometry, Eye development, RNA, sense organs
Abstract: International audience; Glaucoma is the leading cause of irreversible blindness and is usually classified as angle closure and open angle glaucoma (OAG). Primary open angle glaucoma represents the most frequent clinical presentation leading to ganglion cell death and optic nerve degeneration as a main consequence of an intraocular pressure' (IOP) increase. The mechanisms of this IOP increase in such pathology remain unclear but one protein called Myocilin could be a part of the puzzle in the trabecular meshwork (TM). Previously described to be transcriptionally regulated by glucocorticoids, the comprehension of the trabecular regulation of Myocilin' expression has only weakly progressed since 15 years. Due to the essential molecular and cellular implications of retinoids' pathway in eye development and physiology, we investigate the potential role of the retinoic acid in such regulation and expression. This study demonstrates that the global retinoids signaling machinery is present in immortalized TM cells and that Myocilin (MYOC) expression is upregulated by retinoic acid alone or combined with a glucocorticoid co-treatment. This regulation by retinoic acid acts through the MYOC promoter which contains a critical cluster of four retinoic acid responsive elements (RAREs), with the RARE-DR2 presenting the strongest effect and binding the RARα/RXRα heterodimer. All together, these results open up new perspectives for the molecular understanding glaucoma pathophysiology and provide further actionable clues on Myocilin gene regulation.
Published: 2017

39. Detection of the alternative lengthening of telomeres pathway in malignant gliomas for improved molecular diagnosis

Author: Bruno Pereira, Marie-Véronique Demattei, Pierre Verrelle, Jean-Louis Kemeny, Anne Fogli, Julian Biau, Nathalie Grandin, Philippe Arnaud, Emmanuel Chautard, Laetitia Corset, Catherine Godfraind, Michel Charbonneau, Catherine Vaurs-Barrière, T. Khalil, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Cancer Resistance Exploring and Targeting (CREaT), Université d'Auvergne - Clermont-Ferrand I (UdA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de pathologie, Laboratoire de Neuropathologie, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Clinique Saint-Luc, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Neurochirurgie [CHU Clermont-Ferrand], Image Guided Clinical Neurosciences and Connectomics (IGCNC), Génétique, Reproduction et Développement (GReD), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Etude des Parasites Génétiques (LEPG), Université de Tours, Université de Tours-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), service d’anatomopathologie, Centre Hospitalier Universitaire Gabriel Montpied, Laboratoire de Pathologie, Université Catholique de Louvain (UCL)-Clinique Saint-Luc, Délégation à la Recherche Clinique et à l’Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Neurochirurgie A [Clermont-Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin, CRLCC Jean Perrin, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de Biochimie Médicale et Biologie Moléculaire [CHU Clermont-Ferrand], Génétique, Reproduction et Développement - Clermont Auvergne ( GReD ), IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), UMR 6239, Equipe Cellules usine, Ingénierie des protéines et Bio-informatique, Université Francois Rabelais [Tours]-Centre National de la Recherche Scientifique ( CNRS ), Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Cancer Resistance Exploring and Targeting ( CREaT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Université Catholique de Louvain ( UCL ) -Clinique Saint-Luc, Biostat Unit, Image Guided Clinical Neurosciences and Connectomics ( IGCNC ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), and CHAUTARD, Emmanuel
Subjects: 0301 basic medicine, Male, Cancer Research, Telomerase, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, Exon, chemistry.chemical_compound, DNA Modification Methylases, ComputingMilieux_MISCELLANEOUS, Mutation, Brain Neoplasms, Brain, Methylation, Glioma, Middle Aged, Isocitrate Dehydrogenase, 3. Good health, Neurology, Oncology, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Female, Adult, X-linked Nuclear Protein, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Extrachromosomal DNA, Cell Line, Tumor, medicine, Humans, ATRX, Tumor Suppressor Proteins, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Telomere Homeostasis, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Molecular biology, Telomere, 030104 developmental biology, DNA Repair Enzymes, chemistry, RNA, Neurology (clinical), Neoplasm Grading, DNA
Abstract: International audience; Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice. The presence of C-circles significantly correlated with IDH1/2 mutation, MGMT exon 1 methylation, low Ki-67 immunostaining, increased telomeric DNA content, absence of functional ATRX protein and level of HTERT gene expression. In multivariate analysis, we observed a trend to a correlation between elevated TERRA levels and increased survival. Interestingly, the C-circles assay allowed to detect ALT activation in glioblastomas exhibiting wild-type IDH1/2 and ATRX expression. These results suggest that, after the correlations uncovered here have been confirmed on larger numbers of tumors, telomeric markers might be useful in improving diagnosis. They also point out to the utility of using the specific, sensitive and quantitative C-circle and Telo/Alu assays that can work with as few as 30 ng of tumor DNA
Published: 2017

40. Evaluation of the time required to complete a cataract training program on EyeSi surgical simulator during the first-year residency

Author: Thibaud Mathis, Romain Mouchel, Jean Malecaze, Thibaud Garcin, Thibaud Mautuit, Laurent Kodjikian, Carole Burillon, Loïc Druette, Philippe Denis, Hospices Civils de Lyon (HCL), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Hôpital Edouard Herriot [CHU - HCL], Université de Lyon, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Ophthalmology, [PHYS.PHYS]Physics [physics]/Physics [physics], phacoemulsification, virtual reality, General Medicine, medical education, simulation, Cataract, training program
Abstract: Purpose To evaluate the time required to complete a cataract training program for first-year ophthalmology residents using the EyeSi simulator. In addition, evaluate whether the simulator improves virtual performance of cataract surgery during the program. Methods We prospectively included first-year ophthalmology residents who had no experience of cataract surgery. The EyeSi simulator was used, and residents were able to follow the cataract training program, including course A (the easiest) through to course D (the hardest). In course B and above, a “cataract challenge” is proposed to the trainee every hour of simulation. Results A total of 24 participants were included in the study. During the study period, the mean (SD) total time spent on the surgical simulator was 815.6 (174.7) minutes. All the participants completed courses A and B within a mean (SD) of 366.7 (108.0) minutes. A total of 22 residents (91.7%) residents completed course C, and 5 (20.8%) course D. The mean (SD) best score on cataract challenge was 445.6/500 (40.2; range: 330–493) and was obtained in a mean (SD) 7.6 (2.6) attempts. All the residents obtained a score ≥ 60%. The best score in cataract challenge was not correlated to the time spent to achieve courses A and B (r = -0.37, p = 0.0726). Conclusions The time required to complete a basic cataract training program is possible during the first-year residency. The scores obtained in the cataract challenge also increased during the training program and should lead to better surgery skills in these young ophthalmologists.
Published: 2022

41. mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD)

Author: T. Dumontet, Jean-Christophe Pointud, Pierre Val, Anne-Marie Lefrançois-Martinez, Constantine A. Stratakis, Jérôme Bertherat, Frédérique Tissier, Coralie Drelon, Isabelle Sahut-Barnola, Cyrille de Joussineau, M. Batisse-Lignier, Igor Tauveron, Antoine Martinez, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Section on Endocrinology and Genetics, National Institutes of Health (NIH)-National Institute of Child Health and Human Development, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Pôle Endocrinologie-Diabétologie Adultes-Enfants, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), de Joussineau, Cyrille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Génétique, reproduction et développement (GReD), Université Blaise Pascal - Clermont-Ferrand 2 (UBP) - Université d'Auvergne - Clermont-Ferrand I (UdA) - IFR79 - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP] - Hôpital Saint-Vincent de Paul, National Institutes of Health (NIH) - National Institute of Child Health and Human Development, Service d'Endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP] - Centre de Référence pour les Maladies Rares, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Cochin [AP-HP]-Centre de Référence pour les Maladies Rares, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Centre de Référence pour les Maladies Rares
Subjects: Adrenal Cortex Diseases, Male, Tumor suppressor gene, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Hyperphosphorylation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], mTORC1, Mechanistic Target of Rapamycin Complex 1, Biology, Gene Knockout Techniques, Mice, 03 medical and health sciences, 0302 clinical medicine, Adrenocorticotropic Hormone, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cell Line, Tumor, Genetics, Animals, Humans, Phosphorylation, Protein kinase A, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), PI3K/AKT/mTOR pathway, 030304 developmental biology, Sirolimus, 0303 health sciences, TOR Serine-Threonine Kinases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Articles, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell biology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Disease Models, Animal, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Multiprotein Complexes, 030220 oncology & carcinogenesis, bcl-Associated Death Protein, Signal transduction, Signal Transduction, Primary pigmented nodular adrenocortical disease
Abstract: International audience; : Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1α of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which results in increased resistance to apoptosis that contributes to the tumorigenic process. We used in vitro and in vivo models to investigate the possibility of a crosstalk between PKA and mammalian target of rapamycin (mTOR) pathways in adrenocortical cells and its possible involvement in apoptosis resistance. Impact of PKA signaling on activation of the mTOR pathway and apoptosis was measured in a mouse model of PPNAD (AdKO mice), in human and mouse adrenocortical cell lines in response to pharmacological inhibitors and in PPNAD tissues by immunohistochemistry. AdKO mice showed increased mTOR complex 1 (mTORC1) pathway activity. Inhibition of mTORC1 by rapamycin restored sensitivity of adrenocortical cells to apoptosis in AdKO but not in wild-type mice. In both cell lines and mouse adrenals, rapid phosphorylation of mTORC1 targets including BAD proapoptotic protein was observed in response to PKA activation. Accordingly, BAD hyperphosphorylation, which inhibits its proapoptotic activity, was increased in both AdKO mouse adrenals and human PPNAD tissues. In conclusion, mTORC1 pathway is activated by PKA signaling in human and mouse adrenocortical cells, leading to increased cell survival, which is correlated with BAD hyperphosphorylation. These alterations could be causative of tumor formation.
Published: 2014

42. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development

Author: Drelon, Coralie, Berthon, Annabel, Sahut-Barnola, Isabelle, Mathieu, Mickael, Dumontet, Typhanie, Rodriguez, Stéphanie, Batisse-Lignier, Marie, Tabbal, Houda, Tauveron, Igor, Martinez, Anne-Marie, Pointud, Jean-Christophe, Gomez-Sanchez, Celso, Vainio, Seppo, Shan, Jingdong, Val, Sonia, Val, Andreas, Stratakis, Constantine, Martinez, Antoine, VAL, Pierre, Lefrançois-Martinez, Marie, Sacco, Sonia, Schedl, Andreas, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, University of Mississippi Medical Center (UMMC), Laboratory of Developmental Biology, Department of Medical Biochemistry and Molecular Biology, University of Oulu and Biocenter Oulu, Section on Endocrinology and Genetics, National Institutes of Health (NIH)-National Institute of Child Health and Human Development, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Universitaire Lorrain d'Histoire (CRULH), Université de Lorraine (UL), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique du développement normal et pathologique, and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Carcinogenesis, Cellular differentiation, MESH: beta Catenin, Adrenal Gland Neoplasms, General Physics and Astronomy, MESH: Zona Fasciculata, Mice, chemistry.chemical_compound, WNT4, MESH: Animals, Phosphorylation, Wnt Signaling Pathway, beta Catenin, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, Aldosterone, biology, Adrenal cortex, Wnt signaling pathway, MESH: Wnt Signaling Pathway, Cell Differentiation, MESH: Carcinogenesis, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Cell biology, medicine.anatomical_structure, Female, Zona Glomerulosa, MESH: Cell Differentiation, endocrine system, medicine.medical_specialty, Beta-catenin, MESH: Cell Line, Tumor, MESH: Zona Glomerulosa, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Cyclic AMP-Dependent Protein Kinases, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Zona fasciculata, Cell Line, Tumor, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, MESH: Mice, MESH: Humans, MESH: Phosphorylation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Chemistry, Cyclic AMP-Dependent Protein Kinases, MESH: Adrenal Gland Neoplasms, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Endocrinology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, chemistry, Zona glomerulosa, biology.protein, Zona Fasciculata, MESH: Female
Abstract: Adrenal cortex physiology relies on functional zonation, essential for production of aldosterone by outer zona glomerulosa (ZG) and glucocorticoids by inner zona fasciculata (ZF). The cortex undergoes constant cell renewal, involving recruitment of subcapsular progenitors to ZG fate and subsequent lineage conversion to ZF identity. Here we show that WNT4 is an important driver of WNT pathway activation and subsequent ZG differentiation and demonstrate that PKA activation prevents ZG differentiation through WNT4 repression and WNT pathway inhibition. This suggests that PKA activation in ZF is a key driver of WNT inhibition and lineage conversion. Furthermore, we provide evidence that constitutive PKA activation inhibits, whereas partial inactivation of PKA catalytic activity stimulates β-catenin-induced tumorigenesis. Together, both lower PKA activity and higher WNT pathway activity lead to poorer prognosis in adrenocortical carcinoma (ACC) patients. These observations suggest that PKA acts as a tumour suppressor in the adrenal cortex, through repression of WNT signalling., The adrenal cortex undergoes functional zonation to generate an outer zona glomerulosa (ZG) and inner zona fasciculata (ZF), but how this is regulated at a molecular level is unclear. Here, the authors show that ZG differentiation is stimulated by WNT signalling and that PKA blocks WNT signalling to allow ZF differentiation and also prevents WNT-induced cancer development.
Published: 2016

43. International Congress on Transposable elements (ICTE 2016) in Saint Malo: mobile elements under the sun of Brittany

Author: Mireille Bétermier, Jean-Nicolas Volff, Chantal Vaury, Michael Chandler, Antoine Bridier-Nahmias, Pascale Lesage, Gaël Cristofari, Nicolas Gilbert, Hadi Quesneville, Séverine Chambeyron, Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Département chimie alimentation santé environnement risque-CNAM ( CASER ), Laboratoire de microbiologie et génétique moléculaires ( LMGM ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche sur le Cancer et le Vieillissement ( IRCAN ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Eloi-Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Unité de Recherche Génomique Info ( URGI ), Institut National de la Recherche Agronomique ( INRA ), Génétique, reproduction et développement ( GReD ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR79-Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), Institut de Génomique Fonctionnelle de Lyon ( IGFL ), École normale supérieure - Lyon ( ENS Lyon ) -Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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 Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Lesage, Pascale, and BMC, BMC
Subjects: 0301 basic medicine, Transposable element, lcsh:QH426-470, Evolution of transposable elements, [SDV]Life Sciences [q-bio], education, Control of transposition, Library science, Impact on genomes, Meeting Report, Biology, Mobile DNA, 03 medical and health sciences, Human health, International congress, Molecular Biology, Malo, ComputingMilieux_MISCELLANEOUS, Genetics, [ SDV ] Life Sciences [q-bio], Mechanism of transposition, SAINT, Genome structure, biology.organism_classification, [SDV] Life Sciences [q-bio], lcsh:Genetics, 030104 developmental biology, Transposon-based gene therapy, Transposable elements, Mobile genetic elements
Abstract: International audience; AbstractThe third international conference on Transposable Elements (ICTE) was held 16–19 April 2016 in Saint Malo, France. Organized by the French Transposition Community (Research group of the CNRS: “Mobile genetic elements: from mechanism to populations, an integrative approach”) and the French Society of Genetics, the conference’s goal was to bring together researchers who study transposition in diverse organisms, using multiple experimental approaches. The meeting gathered 180 participants from all around the world. Most of them contributed through poster presentations, invited talks and short talks selected from poster abstracts. The talks were organized into six scientific sessions: “Taming mobile DNA: self and non-self recognition”; “Trans-generational inheritance”; “Mobile DNA genome structure and organization, from molecular mechanisms to applications”; “Remembrance of (retro)transposon past: mobile DNA in genome evolution”; and finally “The yin and the yang of mobile DNA in human health”.
Published: 2016

44. A novel family of plant nuclear envelope-associated proteins

Author: Vidya Pawar, David E. Evans, Katja Graumann, Axel Poulet, Gwénaëlle Détourné, Emmanuel Vanrobays, Christophe Tatout, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Biological and Medical Sciences, Oxford Brookes University, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, 0301 basic medicine, Nuclear Envelope, Physiology, LINC complex, nucleus, Blotting, Western, Arabidopsis, Plant Science, Genes, Plant, 01 natural sciences, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, Two-Hybrid System Techniques, Arabidopsis thaliana, chromatin, Inner membrane, Cloning, Molecular, Transcription factor, Cytoskeleton, Phylogeny, Microscopy, Confocal, biology, Arabidopsis Proteins, Chemistry, nucleoskeleton, Membrane Proteins, nuclear lamina, biology.organism_classification, Chromatin, Cell biology, Transmembrane domain, 030104 developmental biology, Nuclear lamina, inner nuclear membrane, SUN domain, nuclear envelope, 010606 plant biology & botany, higher plant
Abstract: International audience; This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain. AtNEAP proteins localise to the nuclear periphery as part of stable protein complexes, are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex. An A. thaliana cDNA library screen identified a putative transcription factor called AtbZIP18 as a novel interactor of AtNEAP1, which suggest a connection between NEAP and chromatin. An Atneap1 Atneap3 double-knockout mutant showed reduced root growth, and altered nuclear morphology and chromatin structure. Thus AtNEAPs are suggested as inner nuclear membrane-anchored coiled-coil proteins with roles in maintaining nuclear morphology and chromatin structure.
Published: 2016

45. Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology

Author: Lars Björndahl, Christopher L R Barratt, David Mortimer, Ashok Agarwal, Robert J Aitken, Juan G Alvarez, Natalie Aneck-Hahn, Stefan Arver, Elisabetta Baldi, Lluís Bassas, Florence Boitrelle, Riana Bornman, Douglas T Carrell, José A Castilla, Gerardo Cerezo Parra, Jerome H Check, Patricia S Cuasnicu, Sally Perreault Darney, Christiaan de Jager, Christopher J De Jonge, Joël R Drevet, Erma Z Drobnis, Stefan S Du Plessis, Michael L Eisenberg, Sandro C Esteves, Evangelini A Evgeni, Alberto Ferlin, Nicolas Garrido, Aleksander Giwercman, Ilse G F Goovaerts, Trine B Haugen, Ralf Henkel, Lars Henningsohn, Marie-Claude Hofmann, James M Hotaling, Piotr Jedrzejczak, Pierre Jouannet, Niels Jørgensen, Jackson C Kirkman Brown, Csilla Krausz, Maciej Kurpisz, Ulrik Kvist, Dolores J Lamb, Hagai Levine, Kate L Loveland, Robert I McLachlan, Ali Mahran, Liana Maree, Sarah Martins da Silva, Michael T Mbizvo, Andreas Meinhardt, Roelof Menkveld, Sharon T Mortimer, Sergey Moskovtsev, Charles H Muller, Maria José Munuce, Monica Muratori, Craig Niederberger, Cristian O’Flaherty, Rafael Oliva, Willem Ombelet, Allan A Pacey, Michael A Palladino, Ranjith Ramasamy, Liliana Ramos, Nathalie Rives, Eduardo Rs Roldan, Susan Rothmann, Denny Sakkas, Andrea Salonia, Maria Cristina Sánchez-Pozo, Rosanna Sapiro, Stefan Schlatt, Peter N Schlegel, Hans-Christian Schuppe, Rupin Shah, Niels E Skakkebæk, Katja Teerds, Igor Toskin, Herman Tournaye, Paul J Turek, Gerhard van der Horst, Monica Vazquez-Levin, Christina Wang, Alex Wetzels, Theodosia Zeginiadou, Armand Zini, Faculty of Medicine and Pharmacy, Clinical sciences, Biology of the Testis, Centre for Reproductive Medicine - Gynaecology, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Neuroendocrine, Endocrine and Germinal Differentiation Communication (NorDic), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Björndahl, L, Barratt, Clr, Mortimer, D, Agarwal, A, Aitken, Rj, Alvarez, Jg, Aneck-Hahn, N, Arver, S, Baldi, E, Bassas, L, Boitrelle, F, Bornman, R, Carrell, Dt, Castilla, Ja, Cerezo Parra, G, Check, Jh, Cuasnicu, P, Darney, Sp, de Jager, C, De Jonge, Cj, Drevet, Jr, Drobnis, Ez, Du Plessis, S, Eisenberg, Ml, Esteves, Sc, Evgeni, Ea, Ferlin, A, Garrido, N, Giwercman, A, Goovaerts, Igf, Haugen, Tb, Henkel, R, Henningsohn, L, Hofmann, Mc, Hotaling, Jm, Jedrzejczak, P, Jouannet, P, Jørgensen, N, Kirkman Brown, Jc, Krausz, C, Kurpisz, M, Kvist, U, Lamb, Dj, Levine, H, Loveland, Kl, Mclachlan, Ri, Mahran, A, Maree, L, Martins da Silva, S, Mbizvo, Mt, Meinhardt, A, Menkveld, R, Mortimer, St, Moskovtsev, S, Muller, Ch, Munuce, Mj, Muratori, M, Niederberger, C, O'Flaherty, C, Oliva, R, Ombelet, W, Pacey, Aa, Palladino, Ma, Ramasamy, R, Ramos, L, Rives, N, Roldan, Er, Rothmann, S, Sakkas, D, Salonia, A, Sánchez-Pozo, Mc, Sapiro, R, Schlatt, S, Schlegel, Pn, Schuppe, Hc, Shah, R, Skakkebæk, Ne, Teerds, K, Toskin, I, Tournaye, H, Turek, Pj, van der Horst, G, Vazquez-Levin, M, Wang, C, Wetzels, A, Zeginiadou, T, Zini, A., Pacey, Allan/0000-0002-4387-8871, Arver, Stefan/0000-0002-2925-355X, Mortimer, David/0000-0002-0638-2893, Barratt, christopher/0000-0003-0062-9979, Kirkman-Brown, Jackson, C/0000-0003-2833-8970, Bjorndahl, Lars/0000-0002-4709-5807, Baldi, Elisabetta/0000-0003-1808-3097, Aitken, Robert John/0000-0002-9152-156X, Bjorndahl, Lars, Barratt, Christopher L. R., Mortimer, David, Agarwal, Ashok, Aitken, Robert J., Alvarez, Juan G., Aneck-Hahn, Natalie, Arver, Stefan, Baldi, Elisabetta, Bassas, Lluis, Boitrelle, Florence, Bornman, Riana, Carrell, Douglas T., Castilla, Jose A., Cerezo Parra, Gerardo, Check, Jerome H., Cuasnicu, Patricia S., Darney, Sally Perreault, de Jager, Christiaan, De Jonge, Christopher J., Drevet, Joel R., Drobnis, Erma Z., Du Plessis, Stefan S., Eisenberg, Michael L., Esteves, Sandro C., Evgeni, Evangelini A., Ferlin, Alberto, Garrido, Nicolas, Giwercman, Aleksander, Goovaerts, Ilse G. F., Haugen, Trine B., Henkel, Ralf, Henningsohn, Lars, Hofmann, Marie-Claude, Hotaling, James M., Jedrzejczak, Piotr, Jouannet, Pierre, Jorgensen, Niels, Brown, Jackson C. Kirkman, Krausz, Csilla, Kurpisz, Maciej, Kvist, Ulrik, Lamb, Dolores J., Levine, Hagai, Loveland, Kate L., McLachlan, Robert, I, Mahran, Ali, Maree, Liana, da Silva, Sarah Martins, Mbizvo, Michael T., Meinhardt, Andreas, Menkveld, Roelof, Mortimer, Sharon T., Moskovtsev, Sergey, Muller, Charles H., Jose Munuce, Maria, Muratori, Monica, Niederberger, Craig, O'Flaherty, Cristian, Oliva, Rafael, OMBELET, Willem, Pacey, Allan A., Palladino, Michael A., Ramasamy, Ranjith, Ramos, Liliana, Rives, Nathalie, Roldan, Eduardo Rs, Rothmann, Susan, Sakkas, Denny, Salonia, Andrea, Cristina Sanchez-Pozo, Maria, Sapiro, Rosanna, Schlatt, Stefan, Schlegel, Peter N., Schuppe, Hans-Christian, Shah, Rupin, Skakkebaek, Niels E., Teerds, Katja, Toskin, Igor, Tournaye, Herman, Turek, Paul J., van der Horst, Gerhard, Vazquez-Levin, Monica, Wang, Christina, Wetzels, Alex, Zeginiadou, Theodosia, and Zini, Armand
Subjects: Reproducitibility, [SDV]Life Sciences [q-bio], andrology, basic semen examination, journal requirements, laboratory training, patient security, quality control, reproducibility, reproductive medicine, science development, standardized laboratory procedures, Humans, Reproducibility of Results, Publishing, Semen, Semen Analysis, Andrology, Obstetrics & Reproductive Medicine, Biology, 11 Medical and Health Sciences, Reproductive Biology, Science & Technology, Rehabilitation, Obstetrics & Gynecology, Obstetrics and Gynecology, Reproductive Medicine, 16 Studies in Human Society, Human and Animal Physiology, Fysiologie van Mens en Dier, Human medicine, Life Sciences & Biomedicine
Abstract: Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.
Published: 2022

46. Efficacy of Thin and Ultrathin Descemet Stripping Automated Endothelial Keratoplasty and Influence of Graft Thickness on Postoperative Outcomes: Systematic Review and Meta-analysis

Author: Lauren Béal, Valentin Navel, Bruno Pereira, Florent Magnier, Stephanie L. Watson, Julien S. Baker, Frédéric Chiambaretta, Frédéric Dutheil, Service d'Ophtalmologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), The University of Sydney, Sydney Eye Hospital, Hong Kong Baptist University (HKBU), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and Service Santé Travail Environnement [CHU Clermont-Ferrand]
Subjects: Graft Rejection, Ophthalmology, Endothelium, Corneal, Visual Acuity, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Refraction, Ocular, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Descemet Stripping Endothelial Keratoplasty, Corneal Diseases, Retrospective Studies
Abstract: International audience; PurposeTo conduct a systematic review and meta-analysis on the efficacy of thin and ultrathin Descemet stripping automated endothelial keratoplasty (T-DSAEK and UT-DSAEK, with graft thickness 100 μm induced a hyperopic shift. Metaregressions did not demonstrate differences between the 3 groups (100 μm.
Published: 2022

47. Dysregulation of RAGE receptor in Ocular Surface pathology

Author: Navel, Valentin, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université Clermont Auvergne, Frédéric Chiambaretta, and Loïc Blanchon
Subjects: Ophthalmology, Oeil sec, Ophtalmologie, Ocular surface, Surface oculaire, Dry eye disease, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Keratoconus, Kératocone, Rage, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The Receptor for Advanced Glycation End products (RAGE) is a ubiquitous transmembrane receptor involved in several pro-inflammatory activation pathways. The transmembrane form (fl-RAGE) is described to induce the intracellular activation signal, and soluble forms (s-RAGE and es-RAGE) to act as decoys sequestering the ligands. The role of RAGE is well-known in the pathophysiology of diabetic retinopathy, much less in pathologies of the ocular surface such as keratoconus (KC) and dry eye syndrome (DED). Historically defined as an ectatic and non-inflammatory corneal disease, KC seems to trigger or increase with the inflammatory biomarkers (IL-1, IL-6, TNF-α, MMP-9) in the ocular surface. Moreover, in DED, an inflammatory vicious circle within the ocular surface is recognized as a central pathophysiological mechanism, with the instability of the tear film and its hyperosmolarity. In addition, like others barriers tissues, the ocular surface is daily exposed to oxidative stress (i.e. atmospheric pollution or ultraviolet radiation). It is well-known that the RAGE pathway is linked with the unbalance of the oxidative stress in tissues. Thus, in this work, we showed the overexpression of RAGE isoforms in the tissues and tears of subjects with KC compared to healthy subjects. Moreover, in systematic reviews applied to meta-analyses, we synthesized the existing literature to show that there was an imbalance of the oxidative stress in the tissues and tears of the ocular surface of patients with KC and DED. Finally, we developed an animal experimentation model (C57 Black 6 mouses) linked with a study carried out on a cell model (primary cells, corneal and conjunctival cell lines) in order to understand the involvement of RAGE in the physiopathology of dry eye syndrome.; Le Récepteur aux Produits Avancés de Glycation (Receptor for Advanced Glycation End products, RAGE) est un récepteur transmembranaire, ubiquitaire, impliqué dans de nombreuses voies d'activation pro-inflammatoires. On lui décrit une forme transmembranaire (fl-RAGE) qui véhicule le signal d'activation intracellulaire, et des formes solubles (s-RAGE et es-RAGE) qui ont un rôle de leurres en séquestrant les ligands. Le rôle de RAGE est bien connu dans la physiopathologie de la rétinopathie diabétique, beaucoup moins dans des pathologies de la surface oculaire comme le kératocône (KC) et le syndrome sec oculaire (dry eye disease, DED). Longtemps défini comme une pathologie cornéenne ectasiante et non inflammatoire, le KC semble déclenché ou aggravé par des phénomènes inflammatoires au sein de la surface oculaire, comme l'atteste des travaux récents montrant une élévation des biomarqueurs de l'inflammation (IL-1, IL-6, TNF-α, MMP-9). Par ailleurs, dans le DED, un cercle vicieux inflammatoire au sein de la surface oculaire est reconnu comme mécanisme physiopathologique centrale, avec l'instabilité du film lacrymal et son hyperosmolarité. De plus, en qualité de tissus barrières avec notre environnement, la surface oculaire est quotidiennement exposée au stress oxydatif lié à la pollution atmosphérique ou au rayonnement ultra-violet. Il existe un lien d'activation entre les acteurs de la voie RAGE et le déséquilibre de la balance oxydative dans les tissus. Par ce travail, nous avons montré la surexpression des isoformes de RAGE dans les tissus et larmes de sujets atteints de KC par rapport à des sujets sains. Par ailleurs, dans un cadre formel appliqué aux méta-analyses, nous avons synthétisé la littérature existante pour montrer qu'il existait un déséquilibre de la balance oxydative dans les tissus et larmes de la surface oculaire de patients atteints de KC et de DED. Forts de ces résultats, nous avons développé un modèle d'expérimentation animale (souris C57 Black 6) en parallèle d'une étude menée sur modèle cellulaire (cellules primaires et lignées cellulaires cornéennes et conjonctivales) afin de comprendre l'implication de RAGE dans la physiopathologie du syndrome sec oculaire, et notamment les mécanismes inflammatoires impliqués dans sa survenue et chronicisation.
Published: 2023

48. A bicellular fluorescent ductal carcinoma in situ (DCIS)-like tumoroid to study the progression of carcinoma: practical approaches and optimization

Author: Ola Habanjar, Anne-Catherine Maurin, Cyrielle Vituret, Caroline Vachias, Lucie Longechamp, Cécile Garnier, Caroline Decombat, Céline Bourgne, Mona Diab-Assaf, Florence Caldefie-Chezet, Laetitia Delort, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), and Université Libanaise
Subjects: [SDV]Life Sciences [q-bio], Biomedical Engineering, General Materials Science
Abstract: International audience; Recently, many types of 3D culture systems have been developed to preserve the physicochemical environment and biological characteristics of the original tumors better than the conventional 2D monolayer culture system. There are various types of models belonging to this culture, such as the culture based on non-adherent and/or scaffold-free matrices to form the tumors. Agarose mold has been widely used to facilitate tissue spheroid assembly, as it is essentially non-biodegradable, bio-inert, biocompatible, low-cost, and low-attachment material that can promote cell spheroidization. As no studies have been carried out on the development of a fluorescent bicellular tumoroid mimicking ductal carcinoma in situ (DCIS) using human cell lines, our objective was to detail the practical approaches developed to generate this model, consisting of a continuous layer of myoepithelial cells (MECs) around a previously formed in situ breast tumor. The practical approaches developed to generate a bi-cellular tumoroid mimicking ductal carcinoma in situ (DCIS), consisting of a continuous layer of myoepithelial cells (MECs) around a previously formed in situ breast tumoroid. Firstly, the optimal steps and conditions of spheroids generation using a non-adherent agarose gel were described, in particular, the appropriate medium, seeding density of each cell type and incubation period. Next, a lentiviral transduction approach to achieve stable fluorescent protein expression (integrative system) was used to characterize the different cell lines and to track tumoroid generation through immunofluorescence, the organization of the two cell types was validated, specific merits and drawbacks were compared to lentiviral transduction. Two lentiviral vectors expressing either EGFP (Enhanced Green Fluorescent Protein) or m-Cherry (Red Fluorescent Protein) were used. Various rates of a multiplicity of infection (MOI) and multiple types of antibodies (anti-p63, anti-CK8, anti-Maspin, anti-Calponin) for immunofluorescence analysis were tested to determine the optimal conditions for each cell line. At MOI 40 (GFP) and MOI 5 (m-Cherry), the signals were almost homogeneously distributed in the cells which could then be used to generate the DCIS-like tumoroids. Images of the tumoroids in agarose molds were captured with a confocal microscope Micro Zeiss Cell Observer Spinning Disk or with IncuCyte (R) to follow the progress of the generation. Measurement of protumoral cytokines such as IL-6, IL8 and leptin confirmed their secretion in the supernatants, indicating that the properties of our cells were not altered. Finally the advantages and disadvantages of each fluorescent approach were discussed. This model could also be used for other solid malignancies to study the complex relationship between different cells such as tumor and myoepithelial cells in various microenvironments (inflammatory, adipose and tumor, obesity, etc.). Although, this new model is well established to monitor drug screening applications and perform pharmacokinetic and pharmacodynamic analyses.
Published: 2023

49. RTEL1 is required for silencing and epigenome stability

Author: Margaux Olivier, Amy Hesketh, Marie-Noëlle Pouch-Pélissier, Thierry Pélissier, Ying Huang, David Latrasse, Moussa Benhamed, Olivier Mathieu, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: Transcriptional silencing is an essential mechanism for controlling the expression of genes, transgenes and heterochromatic repeats through specific epigenetic marks on chromatin that are maintained during DNA replication. In Arabidopsis, silenced transgenes and heterochromatic sequences are typically associated with high levels of DNA methylation, while silenced genes are enriched in H3K27me3. Reactivation of these loci is often correlated with decreased levels of these repressive epigenetic marks. Here, we report that the DNA helicase REGULATOR OF TELOMERE ELONGATION 1 (RTEL1) is required for transcriptional silencing. RTEL1 deficiency causes upregulation of many genes enriched in H3K27me3 accompanied by a moderate decrease in this mark, but no loss of DNA methylation at reactivated heterochromatic loci. Instead, heterochromatin exhibits DNA hypermethylation and increased H3K27me3 inrtel1. We further find that loss of RTEL1 suppresses the release of heterochromatin silencing caused by the absence of the MOM1 silencing factor. RTEL1 is conserved among eukaryotes and plays a key role in resolving DNA secondary structures during DNA replication. Inducing such aberrant DNA structures using DNA cross-linking agents also results in a loss of transcriptional silencing. These findings uncover unappreciated roles for RTEL1 in transcriptional silencing and in stabilizing DNA methylation and H3K27me3 patterns.
Published: 2023

50. The histone demethylase Kdm3 prevents auto-immune piRNAs production in Drosophila

Author: Karine Casier, Julie Autaa, Nathalie Gueguen, Valérie Delmarre, Pauline P. Marie, Stéphane Ronsseray, Clément Carré, Emilie Brasset, Laure Teysset, Antoine Boivin, Laboratoire de Biologie du Développement [IBPS] (LBD), 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), 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), Génétique, Reproduction et Développement (GReD), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
Subjects: [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Multidisciplinary, [SDV]Life Sciences [q-bio]
Abstract: SUMMARYIn animals, genome integrity of the germ line is protected from transposable element (TE) activity by small, non-coding, dedicated RNAs acting as an immune system against TEs, and called PIWI-interacting RNAs (piRNAs) 1,2. In Drosophila, the production of piRNAs is initiated from heterochromatic loci containing remnants of TEs and enriched in histone H3 trimethylated on lysine 9 (H3K9me3) 3–5. These loci, called piRNA clusters, constitute a memory of past TE invasions. Little is known about how piRNA clusters are genetically defined. Using a genetic screen combined with a bimodal epigenetic state piRNA cluster (BX2), we identified the splicing factor Half pint (Hfp) and the histone demethylase KDM3 as being able to prevent BX2 piRNA production. Furthermore, we showed that Hfp is needed to splice Kdm3 transcripts. Germline expression of Kdm3 coding sequence (splicing-independent) rescued the hfp germline knock-down (GLKD) effect demonstrating that Kdm3 is sufficient to prevent BX2 piRNA production. Our data revealed that in the absence of Kdm3, dozens of gene-containing regions become bona fide germinal dual strand piRNA clusters. Indeed, they produce piRNAs originating from both DNA strands, become transcribed in a Moonshiner-dependent manner and enriched in di-and tri-methylation of lysine 9 of histone H3 (H3K9me2/3) and in Rhino, an HP1-like protein. Eggs laid by Kdm3 GLKD females do not hatch and show developmental defects phenocopying loss of function of genes included into the new piRNA clusters, suggesting an inheritance of functional ovarian “auto-immune” piRNAs. Our results demonstrate that some gene-containing regions are actively prevented for piRNA production by proteins that counteract piRNA cluster emergence. Hence, a non-piRNA-producing state is therefore not a “by default” state but rather a cellular lock that is actively controlled for some genomic loci.KEY FACTSHfp regulates the expression of Kdm3 via its splicingKdm3 prevents genomic regions containing coding genes from becoming piRNA clustersEmbryos from Kdm3 mutant females show developmental phenotypes suggesting that auto-immune piRNAs are functional and alter the expression of genes embedded in newly established piRNA clusters
Published: 2023

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