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8 results on '"Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)"'

1. Common sense model of self-regulation for understanding adherence and quality of life in type 2 diabetes with structural equation modeling

Author

Marie Izaute, Estelle Fall, Igor Tauveron, Salwan Maqdasy, Nadia Chakroun-Baggioni, Philip Böhme, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie - Diabète - Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne (LAPSCO), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Clermont-Ferrand, Clermont-Ferrand, France., 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 LAPSCO, HAL

Subjects
Quality of life, Coping (psychology), media_common.quotation_subject, Type 2 diabetes, Disease, Acceptance and commitment therapy, Structural equation modeling, Self-Control, 03 medical and health sciences, 0302 clinical medicine, Perception, Diabetes mellitus, Surveys and Questionnaires, Adaptation, Psychological, medicine, Humans, 030212 general & internal medicine, Acceptance and Commitment Therapy, media_common, Autobiographical memory, 030503 health policy & services, General Medicine, medicine.disease, 3. Good health, Diabetes Mellitus, Type 2, Latent Class Analysis, Adherence, [SCCO.PSYC] Cognitive science/Psychology, [SCCO.PSYC]Cognitive science/Psychology, Treatment perceptions, Coping, 0305 other medical science, Psychology, Illness perceptions, Clinical psychology
Abstract

International audience; Objectives The objective of the present study was to test the Common Sense Model of self-regulation (CSM) for its relevance for improving adherence and quality of life in type 2 diabetes. Methods A sample of 253 patients with type 2 diabetes was recruited. They completed questionnaires about their perceptions regarding diabetes, coping strategies, therapeutic adherence and quality of life. Their HbA1c levels were also collected. Structural equation modeling (SEM) was used to check the adequacy of our theoretical model (CSM) with the patient data. Results The final model indicated that perceptions were directly and indirectly related to health outcomes through coping strategies and adequately matched the data (χ2 / df = 561/ 220 = 2.55; RMSEA = 0.08; PCFI = 0.66; PGFI = 0.70). Moreover, the model appeared to be identical for both types of treatment (oral and injectable). Conclusions Illness perceptions and coping strategies, or, more specifically, how patients accept disease and think they are able to manage it, significantly affect therapeutic adherence and quality of life in type 2 diabetes. Practice implications These results pave the way for developing psychological treatments aimed at improving patient acceptance and internal resources (e.g. use of autobiographical memory, Acceptance and Commitment Therapy).

Published
2021

2. Bread wheat TaSPO11‐1 exhibits evolutionarily conserved function in meiotic recombination across distant plant species

Author

Alain Nicolas, Giacomo Bastianelli, Emmanuel Guiderdoni, Robin Michard, Ian Fayos, Olivier Da Ines, Charles I. White, Pierre Sourdille, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-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), Génétique Diversité et Ecophysiologie des Céréales (GDEC), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SAS Meiogenix France, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), French government IDEX-ISITE initiative 16-IDEX-0001 (CAP20-25), French National Research Agency (ANR) 2014/1020, CNRS, INSERM, INRAE, Université Clermont Auvergne, 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), Meiogenix, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (Inserm), ANRT CIFRE grant no. 2014/1020, ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Sourdille, Pierre, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, 0301 basic medicine, [SDV]Life Sciences [q-bio], Plant Science, [SDV.GEN] Life Sciences [q-bio]/Genetics, 01 natural sciences, F30 - Génétique et amélioration des plantes, Arabidopsis, [SDV.GEN.GPL] Life Sciences [q-bio]/Genetics/Plants genetics, wheat, Conserved Sequence, Triticum, ComputingMilieux_MISCELLANEOUS, Plant Proteins, 2. Zero hunger, Genetics, meiotic recombination, biology, phytogénétique, food and beverages, Protéine, Complementation, [SDV] Life Sciences [q-bio], Meiosis, Ploidy, Méiose, Spo11, Gene Transfer, Horizontal, Aegilops, SPO11-1, Triticum aestivum, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genes, Plant, Evolution, Molecular, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, Aegilops tauschii, protein evolution, Gene, [SDV.GEN]Life Sciences [q-bio]/Genetics, Génome, Arabidopsis Proteins, fungi, Oryza, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, biology.organism_classification, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, Triticum urartu, grasses, biology.protein, Homologous recombination, Sequence Alignment, 010606 plant biology & botany
Abstract

International audience; The manipulation of meiotic recombination in crops is essential to develop new plant varieties rapidly, helping to produce more cultivars in a sustainable manner. One option is to control the formation and repair of the meiosis-specific DNA double-strand breaks (DSBs) that initiate recombination between the homologous chromosomes and ultimately lead to crossovers. These DSBs are introduced by the evolutionarily conserved topoisomerase-like protein SPO11 and associated proteins. Here, we characterized the homoeologous copies of the SPO11-1 protein in hexaploid bread wheat (Triticum aestivum). The genome contains three SPO11-1 gene copies that exhibit 93-95% identity at the nucleotide level, and clearly the A and D copies originated from the diploid ancestors Triticum urartu and Aegilops tauschii, respectively. Furthermore, phylogenetic analysis of 105 plant genomes revealed a clear partitioning between monocots and dicots, with the seven main motifs being almost fully conserved, even between clades. The functional similarity of the proteins among monocots was confirmed through complementation analysis of the Oryza sativa (rice) spo11-1 mutant by the wheat TaSPO11-1-5D coding sequence. Also, remarkably, although the wheat and Arabidopsis SPO11-1 proteins share only 55% identity and the partner proteins also differ, the TaSPO11-1-5D cDNA significantly restored the fertility of the Arabidopsis spo11-1 mutant, indicating a robust functional conservation of the SPO11-1 protein activity across distant plants. These successful heterologous complementation assays, using both Arabidopsis and rice hosts, are good surrogates to validate the functionality of candidate genes and cDNA, as well as variant constructs, when the transformation and mutant production in wheat is much longer and more tedious.

Published
2020

3. SPO11.2 is essential for programmed double‐strand break formation during meiosis in bread wheat ( Triticum aestivum L.)

Author

Isabelle Nadaud, Hélène Rimbert, Olivier Da Ines, Pierre Sourdille, Fatiha Benyahya, Charles I. White, Génétique Diversité et Ecophysiologie des Céréales - Clermont Auvergne (GDEC), Université Clermont Auvergne (UCA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 Diversité et Ecophysiologie des Céréales (GDEC), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 National de la Recherche Scientifique (CNRS), INRA, INSERM, Universite Clermont Auvergne, IDEX-ISITE initiative [16-IDEX-0001 (CAP20-25)], Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte, Region Hauts-de-France, Region Nouvelle-Aquitaine, ANR-14-CE19-0004,CROC,Contrôle de la fréquence de recombinaison méiotique pour accélérer l'innovation variétales chez les espèces cultivées polyploïdes(2014), European Project: AV0013222, 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 National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sourdille, Pierre, Appel à projets générique - Contrôle de la fréquence de recombinaison méiotique pour accélérer l'innovation variétales chez les espèces cultivées polyploïdes - - CROC2014 - ANR-14-CE19-0004 - Appel à projets générique - VALID, and FEDER [SRESRI 2015] - AV0013222 - INCOMING

Subjects
0106 biological sciences, 0301 basic medicine, DMC1 foci, [SDV]Life Sciences [q-bio], Arabidopsis, [SDV.GEN] Life Sciences [q-bio]/Genetics, Plant Science, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 01 natural sciences, [SDV.GEN.GPL] Life Sciences [q-bio]/Genetics/Plants genetics, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, DNA Breaks, Double-Stranded, Conserved Sequence, Triticum, Plant Proteins, 2. Zero hunger, Genetics, Recombination, Genetic, meiotic recombination, biology, Synapsis, food and beverages, [SDV] Life Sciences [q-bio], Meiosis, double-strand break formation, Ploidy, Genome, Plant, Spo11, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bivalent (genetics), [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, alternative splicing, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, crossover, [SDV.GEN]Life Sciences [q-bio]/Genetics, fungi, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Sequence Analysis, DNA, Diploidy, Tetraploidy, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, Triticum urartu, biology.protein, DMC1, Homologous recombination, Sequence Alignment, DNA Topoisomerases, 010606 plant biology & botany
Abstract

International audience; Meiotic recombination is initiated by formation of DNA double-strand breaks (DSBs). This involves a protein complex that includes in plants the two similar proteins, SPO11-1 and SPO11-2. We analysed the sequences of SPO11-2 in hexaploid bread wheat (Triticum aestivum), as well as in its diploid and tetraploid progenitors. We investigated its role during meiosis using single, double and triple mutants. The three homoeologous SPO11-2 copies of hexaploid wheat exhibit high nucleotide and amino acid similarities with those of the diploids, tetraploids and Arabidopsis. Interestingly, however, two nucleotides deleted in exon-2 of the A copy lead to a premature stop codon and suggest that it encodes a non-functional protein. Remarkably, the mutation was absent from the diploid A-relative Triticum urartu, but present in the tetraploid Triticum dicoccoides and in different wheat cultivars indicating that the mutation occurred after the first polyploidy event and has since been conserved. We further show that triple mutants with all three copies (A, B, D) inactivated are sterile. Cytological analyses of these mutants show synapsis defects, accompanied by severe reductions in bivalent formation and numbers of DMC1 foci, thus confirming the essential role of TaSPO11-2 in meiotic recombination in wheat. In accordance with its 2-nucleotide deletion in exon-2, double mutants for which only the A copy remained are also sterile. Notwithstanding, some DMC1 foci remain visible in this mutant, suggesting a residual activity of the A copy, albeit not sufficient to restore fertility.

Published
2020

4. Sperm cryostorage in a dry tank: An accurate alternative

Author

Florence Brugnon, Laurent Janny, Cyril Bouche, Aurélie Vega, Stéphanie Mestres, Bruno Pereira, Laure Chaput, Hanae Pons-Rejraji, Vorilhon S, Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), service de Biostatistiques, DRCI, Centre Hospitalier Universitaire de Clermont-Ferrand, Laboratoire BDR CECOS - FIV AMP, CHU Estaing [Clermont-Ferrand], Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), and BRUGNON, Florence

Subjects
Adult, Male, Acrosome integrity, [SDV]Life Sciences [q-bio], Human sperm, Liquid phase, Semen, DNA fragmentation, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Semen analysis, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Vitality, General Biochemistry, Genetics and Molecular Biology, Liquid nitrogen tank, 03 medical and health sciences, 0302 clinical medicine, Animal science, Dry tank, medicine, Humans, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Slow freezing, Cryopreservation, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Chemistry, urogenital system, [SDV.BA]Life Sciences [q-bio]/Animal biology, 0402 animal and dairy science, Floor level, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Motility, 04 agricultural and veterinary sciences, General Medicine, Liquid nitrogen, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 040201 dairy & animal science, Sperm, Spermatozoa, [SDV] Life Sciences [q-bio], Dry storage, General Agricultural and Biological Sciences, Cryostorage, Semen Preservation
Abstract

International audience; This prospective study aimed to determine the effects of dry nitrogen cryostorage on human sperm characteristics in comparison with liquid nitrogen cryostorage. For this purpose, 42 men undergoing routine semen analysis (21 normozoospermia and 21 with altered semen parameters) were analyzed. After slow freezing, half of the straws of each sample were randomly stored in liquid and dry tanks, at the top and bottom levels of the latter. After 6 months storage, thawed samples were treated by density gradient centrifugation and sperm characteristics were compared. There was no difference in sperm progressive motility (15.1% ± 14.2% vs. 15.1% ± 12.7%; p = 0.76), sperm vitality (25.5% ± 17.7% vs. 26.2% ± 19%; p = 0.71), percentages of acrosome-reacted spermatozoa (38% ± 8.5% vs. 38.5% ± 7.4%; p = 0.53) and DNA fragmentation spermatozoa (27.3% ± 12.4% vs. 28.5% ± 12.9%, p = 0.47) after cryostorage in the dry or the liquid nitrogen tank. Moreover, we did not observe differences between either cryostorage system for normal and altered sperm samples. This lack of difference was also observed whatever the floor level of cryostorage in the dry tank. The temperature measurement of the dry tank showed a stable temperature at -194 °C throughout storage whatever the storage floor level, guaranteeing the stability of the low temperatures suitable for human sperm storage. Because of its greater safety, dry storage without contact with the liquid phase should be preferred and can be a useful alternative for the cryostorage of human sperm samples.

Published
2020

5. Conserved Small Nucleotidic Elements at the Origin of Concerted piRNA Biogenesis from Genes and lncRNAs

Author

Igor V. Sharakhov, Hugues Roest Crollius, Elise Parey, Emilie Brasset, Silke Jensen, Chantal Vaury, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-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 (UCA), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virginia Polytechnic Institute and State University [Blacksburg], Tomsk State University [Tomsk], This work was supported by the 'Russian Science Foundation' (http://rscf.ru) (15-14-20011 to I.V.S.), the 'Agence Nationale de la Recherche' (https://anr.fr) (ANR-17-CE12-0030 EpiTET to E.B. and C.V.), the 'Fondation ARC pour la Recherche sur le Cancer' (https://www.fondation-arc.org) (PJA 20171206129 to E.B.) and the French government IDEX-ISITE initiative (https://www.gouvernement.fr/idex-isite) (16-IDEX-0001, CAP20-25, to E.B.)., ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Jensen, Silke, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris

Subjects
Male, 0301 basic medicine, Small RNA, malaria mosquitoes, [SDV]Life Sciences [q-bio], Genome, Insect, Genes, Insect, piRNA, germline, Germline, Mice, 0302 clinical medicine, Aedes, Testis, Gene Regulatory Networks, RNA, Small Interfering, lcsh:QH301-705.5, Conserved Sequence, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, long non-coding RNA, General Medicine, Long non-coding RNA, 3. Good health, [SDV] Life Sciences [q-bio], Drosophila melanogaster, Female, RNA, Long Noncoding, Regulatory Pathway, endocrine system, Piwi-interacting RNA, Computational biology, Biology, Article, Evolution, Molecular, Biological pathway, 03 medical and health sciences, small RNAs, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Anopheles, Consensus Sequence, Animals, Humans, Gene silencing, Gene, Repetitive Sequences, Nucleic Acid, 030304 developmental biology, urogenital system, Ovary, RNA, Molecular Sequence Annotation, DNA, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, 030104 developmental biology, lcsh:Biology (General), DNA Transposable Elements, 030217 neurology & neurosurgery, Biogenesis
Abstract

PIWI-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing in animal germ cells. The piRNA pathway is increasingly recognized as critical for essential cellular functions such as germline development and reproduction. In the Anopheles gambiae ovary, as much as 11% of piRNAs map to protein-coding genes. Here we show that ovarian mRNAs and long non-coding RNAs (lncRNAs) are processed into piRNAs that can direct other transcripts into the piRNA biogenesis pathway. Targeting piRNAs fuel transcripts either into the ping-pong cycle of piRNA amplification or into the machinery of phased piRNA biogenesis, thereby creating networks of inter-regulating transcripts. RNAs of the same network share related genomic repeats. These repeats give rise to piRNAs, which target other transcripts and lead to a cascade of concerted RNA slicing. While ping-pong networks are based on repeats of several hundred nucleotides, networks that rely on phased piRNA biogenesis operate through short ∼40-nucleotides long repeats, which we named snetDNAs. Interestingly, snetDNAs are recurring in evolution from insects to mammals. Our study brings to light a new type of a conserved regulatory pathway, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway.AUTHOR SUMMARYSmall RNA molecules are essential actors in silencing mobile genetic elements in animal germ cells. The 24-29-nucleotide-long Piwi-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing. Mosquitoes of the Anopheles gambiae species complex are the principal vectors of malaria, and research on their germline is essential to develop new strategies of vector control by acting on reproduction. In the Anopheles gambiae ovary as much as 11% of piRNAs originate from protein-coding genes. We identified piRNAs which are able to target transcripts from several distinct genes or long non-coding RNAs (lncRNAs), bringing together genic transcripts and lncRNAs in a same regulation network. piRNA targeting induces transcript slicing and production of novel piRNAs, which then target other mRNAs and lncRNAs leading again to piRNA processing, thus resulting in a cascade of RNA slicing and piRNA production. Each network relies on piRNAs originating from repeated genetic elements, present in all transcripts of the same network. Some of these repeats are very short, only ∼40-nucleotides long. We identified similar repeats in all 43 animal species that we analysed, including mosquitoes, flies, arachnidae, snail, mouse, rat and human, suggesting that such regulation networks are recurrent, possibly conserved, in evolutionary history.

Published
2020

6. Differential expression and localisation of TGF-β isoforms and receptors in the murine epididymis

Author

Rachel Guiton, Joël R. Drevet, Allison Voisin, Stephanie Bravard, Fabrice Saez, Christelle Damon-Soubeyrand, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-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), AV was supported by the French ministry of higher education, research, and innovation (MESRI). FS, JRD, and RG received funds from INSERM, CNRS, and MESRI., 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Drevet, Joel, and Bodescot, Myriam

Subjects
Male, 0301 basic medicine, Gene isoform, [SDV]Life Sciences [q-bio], medicine.medical_treatment, lcsh:Medicine, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Transforming Growth Factor beta, Testis, medicine, Animals, Protein Isoforms, lcsh:Science, Receptor, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, ComputingMilieux_MISCELLANEOUS, Epididymis, [SDV.BDD.GAM] Life Sciences [q-bio]/Development Biology/Gametogenesis, [SDV.BDLR.RS] Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 030219 obstetrics & reproductive medicine, Multidisciplinary, lcsh:R, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Peripheral tolerance, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Spermatozoa, Cell biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, 030104 developmental biology, medicine.anatomical_structure, Cytokine, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Infertility, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, lcsh:Q, Receptors, Transforming Growth Factor beta, Signal Transduction, Transforming growth factor
Abstract

Testes produce spermatozoa that transit through and are stored in the epididymis where they acquire their fertilising capacities. Spermatozoa appear in the genital tract at puberty, long after the immune system was trained to self-antigens. As a consequence, this organ has to set strategies to tolerate sperm antigens to avoid autoimmune responses that would specifically target and destroy them. A recent study pointed the Transforming Growth Factor-beta (TGF-β) signalling in the dendritic cells as a crucial mechanism for epididymal tolerance to spermatozoa. In the mouse, TGF-β exists under three isoforms, and three distinct receptors have been described. Using RT-qPCR, immunohistochemistry and ELISA techniques, we investigated the expression and spatial distribution of the epididymal TGF-β isoforms and of their receptors in young and adult mice. We showed that both ligands and receptors were produced by immune and non-immune cells in the epididymis, whatever the age mice have. These data bring new clues as to the mechanisms of peripheral tolerance to sperm cells in the murine epididymis and raise potential other implications of the cytokine isoforms.

Published
2020

7. 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

8. Oxidative DNA damage in mouse sperm chromosomes: Size matters

Author

Kocer, Ayhan, Henry-Berger, Joelle, Noblanc, Anaïs, Champroux, Alexandre, Pogorelcnik, Romain, Guiton, Rachel, Janny, Laurent, Pons-Rejraji, Hanae, Saez, Fabrice, Johnson, Graham D, Krawetz, Stephen A, Alvarez, Juan G, Aitken, R John, Drevet, Joël R, Johnson, Graham D., Krawetz, Stephen A., Alvarez, Juan G., Aitken, R. John, Drevet, Joël R., 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 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 ), Center For Molecular Medicine and Genetics, Wayne State University [Detroit], Biologie du Développement et Reproduction (BDR), 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), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Mines de St Etienne, Clermont Université, 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), NCR Corporation [Dundee], Petroleo y petrochimica, Escuela de chimica (CENTRO DE CATALYSIS), UNIVERSIDAD CENTRAL DE VENEZUELA, 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]), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Sperm DNA integrity, [SDV]Life Sciences [q-bio], Interspersed repeat, In situ hybridization, Biology, medicine.disease_cause, Biochemistry, Chromosomes, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, Mice, 0302 clinical medicine, Physiology (medical), medicine, Animals, Immunoprecipitation, ComputingMilieux_MISCELLANEOUS, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, In Situ Hybridization, Fluorescence, 030304 developmental biology, Short Interspersed Nucleotide Elements, Genetics, Cell Nucleus, 0303 health sciences, Nuclear organization, 030219 obstetrics & reproductive medicine, Chromosome, Embryo, 8-Hydroxy-2′-deoxyguanosine (8-OHdG), Oocyte, Sperm, Spermatozoa, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Oxidative stress, Gamete, Mutational risk, DNA Damage
Abstract

International audience; Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models that display high levels of sperm oxidative DNA damage, a common alteration encountered both in in vivo and in vitro reproduction. Immunoprecipitation of oxidized sperm DNA coupled to deep sequencing showed that mouse chromosomes may be largely affected by oxidative alterations. We show that the vulnerability of chromosomes to oxidative attack inversely correlated with their size and was not linked to their GC richness. It was neither correlated with the chromosome content in persisting nucleosomes nor associated with methylated sequences. A strong correlation was found between oxidized sequences and sequences rich in short interspersed repeat elements (SINEs). Chromosome position in the sperm nucleus as revealed by fluorescent in situ hybridization appears to be a confounder. These data map for the first time fragile mouse sperm chromosomal regions when facing oxidative damage that may challenge the repair mechanisms of the oocyte post-fertilization.

Published
2015

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