Search

Your search keyword '"Nathalie Da Silva"' showing total 6 results
Start Over Author "Nathalie Da Silva" Topic [sdv]life sciences [q-bio]
6 results on '"Nathalie Da Silva"'

1. Mechanisms of myostatin and activin A accumulation in chronic kidney disease

Author

Stanislas Bataille, Laetitia Dou, Marc Bartoli, Marion Sallée, Julien Aniort, Borhane Ferkak, Rania Chermiti, Nathalie McKay, Nathalie Da Silva, Stéphane Burtey, Stéphane Poitevin, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre d'enseignement Cnam Paris (CNAM Paris), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Phocean Nephrology Institute, Clinique Bouchard, ELSAN, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Clermont-Ferrand, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Service d'Evaluation Médicale APHM Marseille

Subjects
Mammals, Transplantation, muscle, [SDV]Life Sciences [q-bio], musculoskeletal system, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Activins, sarcopenia, Mice, Nephrology, myostatin, Animals, Humans, activin A, Renal Insufficiency, Chronic, Muscle, Skeletal, indoxyl sulfate, Indican, chronic kidney disease
Abstract

Background Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance. Methods We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells. Results In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients’ muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes. Conclusion During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.

Published
2022
Full Text
View/download PDF

2. Identification of novel mutations by targeted NGS in Moroccan families clinically diagnosed with a neuromuscular disorder

Author

Rachid Saile, Svetlana Gorokhova, Aymane Bouzidi, Marc Bartoli, Martin Krahn, Valérie Delague, Abdelhamid Barakat, Ghizlane Zouiri, Mathieu Cerino, Khaoula Rochdi, Halima Nahili, Yamna Kriouile, Nathalie Da Silva, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biochimie, environnement et agroalimentaire, URAC 36, FSTM, Université Hassan II Casablanca, Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie et de Biologie Moléculaire [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), and University Hassan II [Casablanca]

Subjects
[SDV]Life Sciences [q-bio], Clinical Biochemistry, Marinesco–Sjögren syndrome, Population, Disease, medicine.disease_cause, Biochemistry, DNA sequencing, symbols.namesake, Medicine, Humans, education, Gene, Spinocerebellar Degenerations, Genetics, Sanger sequencing, education.field_of_study, Mutation, business.industry, Hereditary spastic paraplegia type 35, Biochemistry (medical), Marinesco-Sjogren syndrome, General Medicine, Neuromuscular Diseases, North Africa, medicine.disease, Phenotype, Morocco, Next-generation sequencing, symbols, Heredodegenerative Disorders, Nervous System, business, Neuromuscular disorders
Abstract

International audience; Background and aims: The identification of underlying genes of genetic conditions has expanded greatly in the past decades, which has broadened the field of genes responsible for inherited neuromuscular diseases. We aimed to investigate mutations associated with neuromuscular disorders phenotypes in 2 Moroccan families.Material and methods: Next-generation sequencing combined with Sanger sequencing could assist with under-standing the hereditary variety and underlying disease mechanisms in these disorders. Results: Two novel homozygous mutations were described in this study. The SIL1 mutation is the first identified in the Moroccan population, the mutation was identified as the main cause of Marinesco-Sjogren syndrome in one patient. While the second mutation identified in the fatty acid 2-hydroxylase gene (FA2H) was associated with the Spastic paraplegia 35 in another patient, both transmitted in an autosomal recessive pattern.Discussion and conclusions: These conditions are extremely rare in the North African population and may be underdiagnosed due to overlapping clinical characteristics and heterogeneity of these diseases. We have reported in this study mutations associated with the diseases found in the patients. In addition, we have narrowed the phenotypic spectrum, as well as the diagnostic orientation of patients with neuromuscular disorders, who might have very similar symptoms to other disease groups.

Published
2021
Full Text
View/download PDF

3. A novel bi-allelic loss-of-function mutation in STIM1 expands the phenotype of STIM1-related diseases

Author

Alexandra Salvi, Nathalie Da Silva, Nicolas Lévy, Jon Andoni Urtizberea, Marc Bartoli, Catherine Robert, André Mégarbané, Moiz Bakhiet, Valérie Delague, Cristina Skrypnyk, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Arabian Gulf University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jérôme Lejeune, French Association against Myopathies 'Association Française contre les Myopathies' (AFM) project TRIM-RD, the A.MIDEX foundation project RARE-MED and MarMaRa institute., and Bartoli, Marc

Subjects
0301 basic medicine, Male, inorganic chemicals, Ectodermal dysplasia, Adolescent, STIM1, [SDV]Life Sciences [q-bio], Loss of Heterozygosity, 030105 genetics & heredity, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, medicine.disease_cause, Endoplasmic Reticulum, Frameshift mutation, 03 medical and health sciences, Channelopathy, Genetics, medicine, Humans, Stromal Interaction Molecule 1, Genetics (clinical), Exome sequencing, Mutation, Muscles, Homozygote, CRAC, medicine.disease, Store-operated calcium entry, Phenotype, Neoplasm Proteins, [SDV] Life Sciences [q-bio], 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cancer research, Muscle Hypotonia, Calcium, Female, Severe Combined Immunodeficiency, SOCE
Abstract

International audience; STIM1, the stromal interaction molecule 1, is the key protein for maintaining calciumconcentration in the endoplasmic reticulum by triggering the Store Operated CalciumEntry (SOCE). Bi-allelic mutations in STIM1 gene are responsible for a loss-offunctionin patients affected with a CRAC channelopathy syndrome in which severecombined immunodeficiency syndrome (SCID-like), autoimmunity, ectodermal dysplasiaand muscle hypotonia are combined. Here, we studied two siblings from a consanguineousSyrian family, presenting with muscle weakness, hyperlaxity, elastic skin,tooth abnormalities, dysmorphic facies, hypoplastic patellae and history of respiratoryinfections. Using exome sequencing, we have identified a new homozygous frameshiftmutation in STIM1: c.685delT [p.(Phe229Leufs*12)], leading to a complete lossof STIM1 protein. In this study, we describe an unusual phenotype linked to STIM1mutations, combining clinical signs usually observed in different STIM1-related diseases.In particular, we confirmed that the complete loss of STIM1 function is notalways associated with severe immune disorders. Altogether, our results broaden thespectrum of phenotypes associated with mutations in STIM1 and opens new perspectiveson the pathological mechanisms associated with a defect in the proteins constitutingthe SOCE complex.

Published
2021

4. Differences in Mitotic Spindle Architecture in Mammalian Neural Stem Cells Influence Mitotic Accuracy during Brain Development

Author

Nathalie Da Silva, Alexandre D Baffet, Carole Pennetier, Jean-Baptiste Brault, Tristan Piolot, Véronique Marthiens, Ludovic Leconte, Renata Basto, Diana Vargas-Hurtado, CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Compartimentation et dynamique cellulaires (CDC), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Muséfrem, Centre d'Histoire 'Espaces et Cultures' (CHEC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Virology Laboratory, Hôpital Rothchild, and Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
0301 basic medicine, Male, Cell type, [SDV]Life Sciences [q-bio], Neurogenesis, Mitosis, Cell Cycle Proteins, Spindle Apparatus, Biology, Microtubules, General Biochemistry, Genetics and Molecular Biology, Chromosome segregation, 03 medical and health sciences, Mice, 0302 clinical medicine, Neural Stem Cells, Microtubule, Pregnancy, Chromosome Segregation, Animals, Kinetochores, ComputingMilieux_MISCELLANEOUS, Mammals, Embryogenesis, Brain, Embryonic stem cell, Neural stem cell, Cell biology, Spindle apparatus, Mice, Inbred C57BL, 030104 developmental biology, Female, General Agricultural and Biological Sciences, Microtubule-Associated Proteins, 030217 neurology & neurosurgery
Abstract

Summary A functional bipolar spindle is essential to segregate chromosomes correctly during mitosis. Across organisms and cell types, spindle architecture should be optimized to promote error-free divisions. However, it remains to be investigated whether mitotic spindle morphology adapts to changes in tissue properties, typical of embryonic development, in order to ensure different tasks, such as spindle positioning and chromosome segregation. We have characterized mitotic spindles in neural stem cells (NSCs) of the embryonic developing mouse neocortex. Surprisingly, we found a switch in spindle morphology from early to late neurogenic stages, which relies on an increase in inner spindle microtubule density and stability. Mechanistically, we identified the microtubule-associated protein TPX2 as one determinant of spindle shape, contributing not only to its robustness but also to correct chromosome segregation upon mitotic challenge. Our findings highlight a possible causal relationship between spindle architecture and mitotic accuracy with likely implications in brain size regulation.

Published
2018
Full Text
View/download PDF

5. Does overexpression of the Strawberry Notch homolog 2 gene in Dopachrome tautomerase expressing cells trigger a defect in melanoblast specification ?

Author

Edouard Reyes-Gomez, Nathalie da Silva, Stéphanie Gadin-Czerw, J Panthier, Jean-Jacques J., Geneviève Aubin-Houzelstein, Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), ProdInra, Migration, and European Society for Pigment Cell. Bruxelles, BEL.

Subjects
[SDV] Life Sciences [q-bio], Strawberry Notch homolog 2 (Sbno2), sno gene, candidate gene, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2011
Full Text
View/download PDF

6. Missense Mutations in SLC26A8, Encoding a Sperm-Specific Activator of CFTR, Are Associated with Human Asthenozoospermia

Author

Thierry Bienvenu, Pierre F. Ray, Nathalie Da Silva, Mathilde Jollivet, Aminata Touré, Pierre Tufféry, Baptiste Rode, Denise Escalier, Gérard Gacon, Emmanuel Dulioust, Frédéric Becq, Jean-Philippe Wolf, Caroline Norez, Thassadite Dirami, Natacha Gaitch, 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), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie et Génétique Moléculaire, Université Paris Descartes - Paris 5 (UPD5), Molécules Thérapeutiques in silico (MTI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Histologie-Embryologie, Biologie de la Reproduction (CECOS Paris Cochin), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AGeing and IMagery (AGIM), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Université Joseph Fourier - Grenoble 1 (UJF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Morillon, Christelle, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de physiologie et biologie cellulaires ( IPBC ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Descartes - Paris 5 ( UPD5 ), Molécules Thérapeutique in silico, Recherche de molécules à visée thérapeutique par approches In Silico ( MTI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Histologie-Embryologie, Biologie de la Reproduction ( CECOS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], AGeing and IMagery ( AGIM ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Joseph Fourier - Grenoble 1 ( UJF )

Subjects
Male, MESH : Immunohistochemistry, [SDV]Life Sciences [q-bio], MESH: Cricetinae, Cystic Fibrosis Transmembrane Conductance Regulator, Antiporters, MESH : Antiporters, 0302 clinical medicine, MESH: Cricetulus, Cricetinae, MESH : CHO Cells, Missense mutation, Genetics(clinical), MESH: Animals, MESH : Immunoblotting, Genetics (clinical), Sperm motility, Genetics, MESH: Cystic Fibrosis Transmembrane Conductance Regulator, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Immunoblotting, Chinese hamster ovary cell, MESH: Spermatozoa, MESH : Cricetinae, MESH: Genetic Predisposition to Disease, MESH: Anion Transport Proteins, MESH: Sperm Motility, Immunohistochemistry, Spermatozoa, Cystic fibrosis transmembrane conductance regulator, Transport protein, [SDV] Life Sciences [q-bio], Sulfate Transporters, Asthenozoospermia, MESH: Sperm Capacitation, Sperm Motility, MESH : Asthenozoospermia, MESH : Sperm Capacitation, MESH : Male, Urology, MESH : Cricetulus, Immunoblotting, Anion Transport Proteins, Mutation, Missense, CHO Cells, Biology, 03 medical and health sciences, Cricetulus, MESH: CHO Cells, Capacitation, Report, MESH : Spermatozoa, medicine, Animals, Humans, Genetic Predisposition to Disease, 030304 developmental biology, MESH: Mutation, Missense, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, Activator (genetics), MESH : Cystic Fibrosis Transmembrane Conductance Regulator, MESH : Humans, MESH: Immunohistochemistry, medicine.disease, Sperm, Molecular biology, MESH: Male, MESH: Asthenozoospermia, MESH : Sperm Motility, MESH : Anion Transport Proteins, biology.protein, MESH : Genetic Predisposition to Disease, MESH: Antiporters, MESH : Animals, business, Sperm Capacitation, MESH : Mutation, Missense
Abstract

International audience; The cystic fibrosis transmembrane conductance regulator (CFTR) is present in mature sperm and is required for sperm motility and capacitation. Both these processes are controlled by ions fluxes and are essential for fertilization. We have shown that SLC26A8, a sperm-specific member of the SLC26 family of anion exchangers, associates with the CFTR channel and strongly stimulates its activity. This suggests that the two proteins cooperate to regulate the anion fluxes required for correct sperm motility and capacitation. Here, we report on three heterozygous SLC26A8 missense mutations identified in a cohort of 146 men presenting with asthenozoospermia: c.260G>A (p.Arg87Gln), c.2434G>A (p.Glu812Lys), and c.2860C>T (p.Arg954Cys). These mutations were not present in 121 controls matched for ethnicity, and statistical analysis on a control population of 8,600 individuals (from dbSNP and 1000 Genomes) showed them to be associated with asthenozoospermia with a power > 95%. By cotransfecting Chinese hamster ovary (CHO)-K1 cells with SLC26A8 variants and CFTR, we showed that the physical interaction between the two proteins was partly conserved but that the capacity to activate CFTR-dependent anion transport was completely abolished for all mutants. Biochemical studies revealed the presence of much smaller amounts of protein for all variants, but these amounts were restored to wild-type levels upon treatment with the proteasome inhibitor MG132. Immunocytochemistry also showed the amounts of SLC26A8 in sperm to be abnormally small in individuals carrying the mutations. These mutations might therefore impair formation of the SLC26A8-CFTR complex, principally by affecting SLC26A8 stability, consistent with an impairment of CFTR-dependent sperm-activation events in affected individuals.

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results