39 results on '"Reynier, Pascal"'
Search Results
2. Dominant Optic Atrophy: How to Determine the Pathogenicity of Novel Variants?
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Zehden, Jason A., Raviskanthan, Subahari, Mortensen, Peter W., Ferré, Marc, Reynier, Pascal, Milea, Dan, and Lee, Andrew G.
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- 2022
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3. Dominant Optic Atrophy: How to Determine the Pathogenicity of Novel Variants?
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Zehden, Jason A., Raviskanthan, Subahari, Mortensen, Peter W., Ferré, Marc, Reynier, Pascal, Milea, Dan, and Lee, Andrew G.
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- 2022
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4. Tear metabolomics highlights new potential biomarkers for differentiating between Sjögren's syndrome and other causes of dry eye
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Urbanski, Geoffrey, Assad, Sophie, Chabrun, Floris, Chao de la Barca, Juan Manuel, Blanchet, Odile, Simard, Gilles, Lenaers, Guy, Prunier-Mirebeau, Delphine, Gohier, Philippe, Lavigne, Christian, and Reynier, Pascal
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The lacrimal exocrinopathy of primary Sjögren's syndrome (pSS) is one of the main causes of severe dry eye syndrome and a burden for patients. Early recognition and treatment could prevent irreversible damage to lacrimal glands. The aim of this study was to find biomarkers in tears, using metabolomics and data mining approaches, in patients with newly-diagnosed pSS compared to other causes of dry eye syndrome.
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- 2021
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5. Metabolomic Sexual Dimorphism of the Mouse Brain is Predominantly Abolished by Gonadectomy with a Higher Impact on Females
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Chabrun, Floris, Dieu, Xavier, May-Panloup, Pascale, Chupin, Stéphanie, Bourreau, Jennifer, Henrion, Daniel, Letournel, Franck, Procaccio, Vincent, Bonneau, Dominique, Lenaers, Guy, Mirebeau-Prunier, Delphine, Chao de la Barca, Juan Manuel, and Reynier, Pascal
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The importance of sexual dimorphism of the mouse brain metabolome was recently highlighted, in addition to a high regional specificity found between the frontal cortex, the cerebellum, and the brain stem. To address the origin of this dimorphism, we performed gonadectomy on both sexes, followed by a metabolomic study targeting 188 metabolites in the three brain regions. While sham controls, which underwent the same surgical procedure without gonadectomy, reproduced the regional sexual dimorphism of the metabolome previously identified, no sex difference was identifiable after gonadectomy, through both univariate and multivariate analyses. These experiments also made it possible to identify which sex was responsible for the dimorphism for 35 metabolites. The female sex contributed to the difference for more than 80% of them. Our results show that gonads are the main contributors to the brain sexual dimorphism previously observed, especially in females.
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- 2021
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6. Preliminary Metabolomic Profiling of the Vitreous Humor from Hypothermia Fatalities
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Rousseau, Guillaume, Chao de la Barca, Juan Manuel, Rougé-Maillart, Clotilde, Teresiński, Grzegorz, Chabrun, Floris, Dieu, Xavier, Drevin, Guillaume, Mirebeau-Prunier, Delphine, Simard, Gilles, Reynier, Pascal, and Palmiere, Cristian
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The postmortem diagnosis of hypothermia fatalities is often complex due to the absence of pathognomonic lesions and biomarkers. In this study, potential novel biomarkers of hypothermia fatalities were searched in the vitreous humor of known cases of hypothermia fatalities (n= 20) compared to control cases (n= 16), using a targeted metabolomics approach allowing quantitative detection of 188 metabolites. A robust discriminant model with good predictivity was obtained with the supervised OPLS-DA multivariate analysis, showing a distinct separation between the hypothermia and control groups. This signature was characterized by the decreased concentrations of five metabolites (methionine sulfoxide, tryptophan, phenylalanine, alanine, and ornithine) and the increased concentration of 28 metabolites (21 phosphatidylcholines, 3 sphingomyelins, spermine, citrulline, acetylcarnitine, and hydroxybutyrylcarnitine) in hypothermia fatalities compared to controls. The signature shows similarities with already identified features in serum such as the altered concentrations of tryptophan, acylcarnitines, and unsaturated phosphatidylcholines, revealing a highly significant increased activity of methionine sulfoxide reductase, attested by a low methionine sulfoxide-to-methionine ratio. Our results show a preliminary metabolomics signature of hypothermia fatalities in the vitreous humor, highlighting an increased methionine sulfoxide reductase activity.
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- 2021
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7. Mutations in MTHFRand POLGimpaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis
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Wiedemann, Arnaud, Chery, Céline, Coelho, David, Flayac, Justine, Gueguen, Naïg, Desquiret-Dumas, Valérie, Feillet, François, Lavigne, Christian, Neau, Jean-Philippe, Fowler, Brian, Baumgartner, Matthias R., Reynier, Pascal, Guéant, Jean-Louis, and Oussalah, Abderrahim
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Hereditary spastic paraplegias (HSPs) are characterized by lower extremity spasticity and weakness. HSP is often caused by mutations in SPG genes, but it may also be produced by inborn errors of metabolism. We performed next-generation sequencing of 4813 genes in one adult twin pair with HSP and severe muscular weakness occurring at the same age. We found two pathogenic compound heterozygous variants in MTHFR, including a variant not referenced in international databases, c.197C>T (p.Pro66Leu) and a known variant, c.470G>A (p.Arg157Gln), and two heterozygous pathogenic variants in POLG, c.1760C>T (p.Pro587Leu) and c.752C>T (p.Thr251Ile). MTHFRand POLGmutations were consistent with the severe muscle weakness and the metabolic changes, including hyperhomocysteinemia and decreased activity of both N(5,10)methylenetetrahydrofolate reductase (MTHFR) and complexes I and II of the mitochondrial respiratory chain. These data suggest the potential role of MTHFRand POLGmutations through consequences on mitochondrial dysfunction in the occurrence of spastic paraparesis phenotype with combined metabolic, muscular, and neurological components.
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- 2020
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8. Apparent resistance to thyroid hormones: From biological interference to genetics
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Dieu, Xavier, Sueur, Guillaume, Moal, Valérie, Boux de Casson, Florence, Bouzamondo, Nathalie, Bouhours, Natacha, Briet, Claire, Illouz, Frédéric, Reynier, Pascal, Coutant, Régis, Rodien, Patrice, and Mirebeau-Prunier, Delphine
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Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor β (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor β (THRB)and the TH serum transport proteins (ALB, TTR, SERPINA7).
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- 2019
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9. Lipidomics Reveals Triacylglycerol Accumulation Due to Impaired Fatty Acid Flux in Opa1-Disrupted Fibroblasts.
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Bocca, Cinzia, Kane, Mariame Selma, Veyrat-Durebex, Charlotte, Nzoughet, Judith Kouassi, Chao de la Barca, Juan Manuel, Chupin, Stephanie, Alban, Jennifer, Procaccio, Vincent, Bonneau, Dominique, Simard, Gilles, Lenaers, Guy, Reynier, Pascal, and Chevrollier, Arnaud
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- 2019
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10. Metabolomic Profiling of Aqueous Humor in Glaucoma Points to Taurine and Spermine Deficiency: Findings from the Eye‑D Study.
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Buisset, Adrien, Gohier, Philippe, Leruez, Stéphanie, Muller, Jeanne, Amati-Bonneau, Patrizia, Lenaers, Guy, Bonneau, Dominique, Simard, Gilles, Procaccio, Vincent, Annweiler, Cédric, Milea, Dan, Reynier, Pascal, and Chao de la Barca, Juan Manuel
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- 2019
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11. Retinal Neuronal Loss in Visually Asymptomatic Patients With Myoclonic Epilepsy With Ragged-Red Fibers.
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Najjar, Raymond P., Reynier, Pascal, Caignard, Angélique, Procaccio, Vincent, Amati-Bonneau, Patrizia, Mack, Heather, and Milea, Dan
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Background: Myoclonic epilepsy with ragged-red fibers (MERRF, OMIM, #545000) is a rare neurological condition mostly caused by the m.8344A>G mitochondrial DNA pathogenic variant, which can variably affect multiple tissues, including the retina and optic nerve. We report detection of visually asymptomatic neuroretinal loss in 3 patients with genetically confirmed MERRF, using spectral domain optical coherence tomography (SD-OCT). Methods: All patients underwent a complete ophthalmic examination including assessments of visual acuity, color vision, pupillary reactions, extraocular movements, applanation tonometry, slit-lamp, and dilated fundus examinations. Standard automated perimetry or Goldmann kinetic perimetry was performed, as well as fundus photographs and SD-OCT of the optic nerve head and macula. Results: Despite the absence of visual symptoms in all patients, and normal visual acuity and visual fields in 1 patient, the 3 genetically confirmed patients (point mutations m.8344A>G; age range: 18-62 years) with MERRF-related neurological manifestations, displayed thinning of the retinal nerve fiber layer and variable alterations of the macular ganglion cell complex. Conclusions: Visually asymptomatic patients with genetically confirmed MERRF can display features of structural neuroretinal loss, quantifiable with SD-OCT. Further investigations are needed to establish whether OCT can assess early neurodegeneration in MERRF. [ABSTRACT FROM AUTHOR]
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- 2019
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12. Pathologies liées à des mutations de l'ADN mitochondrial.
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Bris, Céline, Desquiret-Dumas, Valérie, Gueguen, Naig, Amati-Bonneau, Patrizia, Reynier, Pascal, and Procaccio, Vincent
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Résumé Les maladies mitochondriales sont des pathologies fréquentes du métabolisme caractérisées par une forte hétérogénéité clinique et génétique. La double origine génétique des mitochondries, ADN nucléaire et ADN mitochondrial (ADNmt), et l'hétéroplasmie mitochondriale, définie par la coexistence de mitochondries mutées et normales au sein des cellules, sont à l'origine de la complexité du diagnostic de ces maladies. La transmission de l'ADNmt est exclusivement maternelle, ségrégant de manière aléatoire au cours des divisions cellulaires. Ces maladies mitochondriales peuvent survenir à n'importe quel âge de la vie et les présentations cliniques sont extrêmement variables touchant les tissus fortement consommateurs d'énergie comme muscle ou cerveau mais tous les organes sont susceptibles d'être atteints. Plusieurs centaines de mutations de l'ADNmt ont pu être ainsi identifiées responsables de pathologies mitochondriales. Différents types de mutations de l'ADNmt, mutations ponctuelles, délétions ou déplétion de l'ADNmt ont pu être répertoriés. Le développement des nouvelles technologies de séquenéage haut débit a considérablement amélioré le diagnostic permettant une analyse systématique de l'ADNmt avec une plus grande sensibilité dans la détection des variants. Cette analyse a révélé en même temps une plus grande complexité de l'analyse et interprétation des variants de l'ADNmt avec la nécessité de développer de nouveaux outils bioinformatiques dédiés à la génétique mitochondriale. Abstract Mitochondrial diseases are common metabolic disorders characterized by a large clinical and genetic heterogeneity. The double genetic origin of mitochondria, nuclear DNA and mitochondrial DNA (mtDNA) and mitochondrial heteroplasmy defined by the coexistence of mutated and normal mitochondria within cells are at the origin of the complexity of the diagnosis of these diseases. The inheritance of mtDNA is exclusively maternal, segregating randomly during cell divisions. These mitochondrial diseases can occur at any age and the clinical presentations are extremely variable affecting high energy demand tissues such as muscle or brain but all organs are likely to be affected. Several hundred mutations of mtDNA could thus be identified responsible for mitochondrial diseases with different types of mutations of the mtDNA such as point mutations, deletions or mtDNA depletion. The recent development of high-throughput sequencing technologies has significantly improved the diagnosis of mitochondrial disorders allowing a systematic analysis of the mtDNA with greater sensitivity in the variant detection but revealed at the same time a greater complexity of the analysis and interpretation of the mtDNA variants with the need to develop new bioinformatics tools dedicated to mitochondrial genetics. [ABSTRACT FROM AUTHOR]
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- 2018
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13. Study of mitochondrial function in placental insufficiency.
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Lefebvre, Tiphaine, Roche, Ombeline, Seegers, Valérie, Cherif, Majida, Khiati, Salim, Gueguen, Naïg, Desquiret-Dumas, Valérie, Geffroy, Guillaume, Blanchet, Odile, Reynier, Pascal, Legendre, Guillaume, Lenaers, Guy, Procaccio, Vincent, and Gascoin, Géraldine
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Introduction: It has been suggested that mitochondria play a crucial role in sustaining pregnancy and foetal growth. The aim of the study was to assess the influence of mitochondrial functions and genetics on placental insufficiency diseases.Methods: A total of 115 patients were recruited, subdivided into 74 placenta samples and 41 maternal blood samples: placental insufficiency diseases including intra uterine growth restriction (IUGR) (n = 35), preeclampsia (PE) (n = 13), IUGR associated to PE (PER) (n = 25); and controls (n = 42). Haplogroups were determined for all patients. Eighty-six placenta samples were studied for quantitative and qualitative analyses of mtDNA: IUGR (n = 25), PE (n = 1), PER (n = 18) and controls (n = 42). Sixteen placenta samples were selected for functional analysis: IUGR (n = 6), PER (n = 2) and controls (n = 8).Results: Mitochondrial DNA copy numbers and rearrangements and haplogroup distribution were not significantly altered in the patient group. Enzyme activity and expression of respiratory chain complexes were also comparable between both groups.Discussion: Our results do not argue in favour of a mitochondrial involvement in placental insufficiency, suggesting that the glycolytic pathway may represent a key energetic source in placental insufficiency diseases. [ABSTRACT FROM AUTHOR]- Published
- 2018
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14. Metabolomics and Lipidomics Profiling of a Combined Mitochondrial Plus Endoplasmic Reticulum Fraction of Human Fibroblasts: A Robust Tool for Clinical Studies.
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Veyrat-Durebex, Charlotte, Bocca, Cinzia, Chupin, Stéphanie, Nzoughet, Judith Kouassi, Simard, Gilles, Lenaers, Guy, Reynier, Pascal, and Blasco, Hélène
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- 2018
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15. Lipidomics Reveals Triacylglycerol Accumulation Due to Impaired Fatty Acid Flux in Opa1-Disrupted Fibroblasts
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Bocca, Cinzia, Kane, Mariame Selma, Veyrat-Durebex, Charlotte, Nzoughet, Judith Kouassi, Chao de la Barca, Juan Manuel, Chupin, Stephanie, Alban, Jennifer, Procaccio, Vincent, Bonneau, Dominique, Simard, Gilles, Lenaers, Guy, Reynier, Pascal, and Chevrollier, Arnaud
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OPA1 is a dynamin GTPase implicated in mitochondrial membrane fusion. Despite its involvement in lipid remodeling, the function of OPA1 has never been analyzed by whole-cell lipidomics. We used a nontargeted, reversed-phase lipidomics approach, validated for cell cultures, to investigate OPA1-inactivated mouse embryonic fibroblasts (Opa1–/–MEFs). This led to the identification of a wide range of 14 different lipid subclasses comprising 212 accurately detected lipids. Multivariate and univariate statistical analyses were then carried out to assess the differences between the Opa1–/–and Opa1+/+genotypes. Of the 212 lipids identified, 69 were found to discriminate between Opa1–/–MEFs and Opa1+/+MEFs. Among these lipids, 34 were triglycerides, all of which were at higher levels in Opa1–/–MEFs with fold changes ranging from 3.60 to 17.93. Cell imaging with labeled fatty acids revealed a sharp alteration of the fatty acid flux with a reduced mitochondrial uptake. The other 35 discriminating lipids included phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamine, and sphingomyelins, mainly involved in membrane remodeling, and ceramides, gangliosides, and phosphatidylinositols, mainly involved in apoptotic cell signaling. Our results show that the inactivation of OPA1 severely affects the mitochondrial uptake of fatty acids and lipids through membrane remodeling and apoptotic cell signaling.
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- 2019
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16. Metabolomic Profiling of Aqueous Humor in Glaucoma Points to Taurine and Spermine Deficiency: Findings from the Eye-D Study
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Buisset, Adrien, Gohier, Philippe, Leruez, Stéphanie, Muller, Jeanne, Amati-Bonneau, Patrizia, Lenaers, Guy, Bonneau, Dominique, Simard, Gilles, Procaccio, Vincent, Annweiler, Cédric, Milea, Dan, Reynier, Pascal, and Chao de la Barca, Juan Manuel
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We compared the metabolomic profile of aqueous humor from patients with primary open-angle glaucoma (POAG; n = 26) with that of a group of age- and sex-matched non-POAG controls (n = 26), all participants undergoing cataract surgery. Supervised paired partial least-squares discriminant analysis showed good predictive performance for test sets with a median area under the receiver operating characteristic of 0.89 and a p-value of 0.0087. Twenty-three metabolites allowed discrimination between the two groups. Univariate analysis after the Benjamini–Hochberg correction showed significant differences for 13 of these metabolites. The POAG metabolomic signature indicated reduced concentrations of taurine and spermine and increased concentrations of creatinine, carnitine, three short-chain acylcarnitines, 7 amino acids (glutamine, glycine, alanine, leucine, isoleucine, hydroxyl-proline, and acetyl-ornithine), 7 phosphatidylcholines, one lysophosphatidylcholine, and one sphingomyelin. This suggests an alteration of metabolites involved in osmoprotection (taurine and creatinine), neuroprotection (spermine, taurine, and carnitine), amino acid metabolism (7 amino acids and three acylcarnitines), and the remodeling of cell membranes drained by the aqueous humor (hydroxyproline and phospholipids). Five of these metabolic alterations, already reported in POAG plasma, concern spermine, C3 and C4 acylcarnitines, PC aa 34:2, and PC aa 36:4, thus highlighting their importance in the pathogenesis of glaucoma.
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- 2019
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17. Liquid chromatography-tandem mass spectrometry for monitoring vitamin D hydroxymetabolites in human aqueous humorElectronic supplementary information (ESI) available. See DOI: 10.1039/c9ay01896d
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Fabregat-Cabello, Neus, Darimont, Pierre, Huyghebaert, Loreen, Reynier, Pascal, Annweiler, Cédric, Milea, Dan, Le Goff, Caroline, and Cavalier, Étienne
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A stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of 24,25-dihydroxyvitamin D3(24,25(OH)2D3) and 25-hydroxyvitamin D3/D2(25(OH)D3/D2) in human aqueous humor samples from the Eye-D study. Optimum sample preparation is based on simple liquid–liquid extraction (LLE) followed by derivatization with an Amplifex reagent prior to LC-MS/MS in order to enhance analyte sensitivity. The average recoveries for 24,25(OH)2D3(0.02, 0.05, 0.4 μg L−1), 25(OH)D3(0.2, 0.5,3.75 μg L−1) and 25(OH)D2(0.15, 0.4, 3 μg L−1) ranged from 92 to 112 with a coefficient of variance (CV) lower than 15%. The limits of quantitation (LOQs) were from 0.02 μg L−1(24,25(OH)2D3) to 0.2 μg L−1(25(OH)D3) using a sample volume of 50 μL. We demonstrated that the present method provides adequate sensitivity, selectivity, accuracy, and robustness to screen for vitamin D metabolites in aqueous humor samples by analyzing five samples which were withdrawn during cataract operation.
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- 2019
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18. A Nontargeted UHPLC-HRMS Metabolomics Pipeline for Metabolite Identification: Application to Cardiac Remote Ischemic Preconditioning.
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Kouassi Nzoughet, Judith, Bocca, Cinzia, Simard, Gilles, Prunier-Mirebeau, Delphine, Chao de la Barca, Juan Manuel, Bonneau, Dominique, Procaccio, Vincent, Prunier, Fabrice, Lenaers, Guy, and Reynier, Pascal
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- 2017
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19. Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults
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Charif, Majida, Nasca, Alessia, Thompson, Kyle, Gerber, Sylvie, Makowski, Christine, Mazaheri, Neda, Bris, Céline, Goudenège, David, Legati, Andrea, Maroofian, Reza, Shariati, Gholamreza, Lamantea, Eleonora, Hopton, Sila, Ardissone, Anna, Moroni, Isabella, Giannotta, Melania, Siegel, Corinna, Strom, Tim M., Prokisch, Holger, Vignal-Clermont, Catherine, Derrien, Sabine, Zanlonghi, Xavier, Kaplan, Josseline, Hamel, Christian P., Leruez, Stephanie, Procaccio, Vincent, Bonneau, Dominique, Reynier, Pascal, White, Frances E., Hardy, Steven A., Barbosa, Inês A., Simpson, Michael A., Vara, Roshni, Perdomo Trujillo, Yaumara, Galehdari, Hamind, Deshpande, Charu, Haack, Tobias B., Rozet, Jean-Michel, Taylor, Robert W., Ghezzi, Daniele, Amati-Bonneau, Patrizia, and Lenaers, Guy
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IMPORTANCE: Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. OBJECTIVE: To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. DESIGN, SETTING, AND PARTICIPANTS: This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed—at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)—to clarify the molecular diagnosis of patients. Each patient’s neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. MAIN OUTCOMES AND MEASURES: Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. RESULTS: Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities on magnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and very rare homozygous and compound heterozygous mutations were identified that led to the absence of the protein and complex I disassembly as well as mild mitochondrial network fragmentation. CONCLUSIONS AND RELEVANCE: A broad clinical spectrum of neurologic features, ranging from isolated optic atrophy to severe early-onset encephalopathies, is associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening in both syndromic neurologic presentations and nonsyndromic recessive optic neuropathies.
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- 2018
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20. Metabolomics and Lipidomics Profiling of a Combined Mitochondrial Plus Endoplasmic Reticulum Fraction of Human Fibroblasts: A Robust Tool for Clinical Studies
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Veyrat-Durebex, Charlotte, Bocca, Cinzia, Chupin, Stéphanie, Kouassi Nzoughet, Judith, Simard, Gilles, Lenaers, Guy, Reynier, Pascal, and Blasco, Hélène
- Abstract
Mitochondria and endoplasmic reticulum (ER) are physically and functionally connected. This close interaction, via mitochondria-associated membranes, is increasingly explored and supports the importance of studying these two organelles as a whole. Metabolomics and lipidomics are powerful approaches for the exploration of metabolic pathways that may be useful to provide deeper information on these organelles’ functions, dysfunctions, and interactions. We developed a quick and simple experimental procedure for the purification of a mitochondria-ER fraction from human fibroblasts. We applied combined metabolomics and lipidomics analyses by mass spectrometry with excellent reproducibility. Seventy-two metabolites and 418 complex lipids were detected with a mean coefficient of variation around 12%, among which many were specific to the mitochondrial metabolism. Thus this strategy based on robust mitochondria-ER extraction and “omics” combination will be useful for investigating the pathophysiology of complex diseases.
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- 2017
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21. Neurotoxicity of Insecticides
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Cassereau, Julien, Ferré, Marc, Chevrollier, Arnaud, Codron, Philippe, Verny, Christophe, Homedan, Chadi, Lenaers, Guy, Procaccio, Vincent, May-Panloup, Pascale, and Reynier, Pascal
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Background: Human exposure to insecticides raises serious public health concerns worldwide. Insecticides constitute a wide-ranging heterogeneous group of chemicals, most of which target the nervous system and disrupt neurometabolism and/or neurotransmission. Although the acute effects of insecticide poisoning in humans are well documented, the chronic and long-term effects remain difficult to investigate. Objectives and Method: We sought to review the present state-of-knowledge of acute, chronic, neurodevelopmental and neurological consequences of human exposure to insecticides. Results: Animal and epidemiologic studies indicate cognitive, behavioral and psychomotor alterations in mammals chronically exposed to insecticides. Parkinson's and Alzheimer's diseases, amyotrophic lateral sclerosis, and depression, have been regularly associated with insecticide exposure. Clinical studies, supported by experiments on animal models, demonstrate the neurotoxic impact of insecticide exposure during the period of cerebral development, the developing brain being particularly vulnerable to the action of insecticides. Moreover, detoxifying systems that are highly polymorph lead to great inter-individual variability in susceptibility to the neurotoxic effects of insecticides. Conclusion: Studies on mild chronic exposure to insecticides suggest significant involvement in the pathogenesis of multifactorial neurological diseases. However, the tardive appearance of neurodegenerative disorders and the large variability of inter-individual susceptibility to neurotoxicants make it difficult to assess the relative contribution of insecticide exposure. Close vigilance should therefore be exercised with regard to possible exposure to insecticides, particularly during the period of cerebral development.
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- 2017
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22. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
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Aung, Tin, Ozaki, Mineo, Lee, Mei Chin, Schlötzer-Schrehardt, Ursula, Thorleifsson, Gudmar, Mizoguchi, Takanori, Igo, Robert P, Haripriya, Aravind, Williams, Susan E, Astakhov, Yury S, Orr, Andrew C, Burdon, Kathryn P, Nakano, Satoko, Mori, Kazuhiko, Abu-Amero, Khaled, Hauser, Michael, Li, Zheng, Prakadeeswari, Gopalakrishnan, Bailey, Jessica N Cooke, Cherecheanu, Alina Popa, Kang, Jae H, Nelson, Sarah, Hayashi, Ken, Manabe, Shin-ichi, Kazama, Shigeyasu, Zarnowski, Tomasz, Inoue, Kenji, Irkec, Murat, Coca-Prados, Miguel, Sugiyama, Kazuhisa, Järvelä, Irma, Schlottmann, Patricio, Lerner, S Fabian, Lamari, Hasnaa, Nilgün, Yildirim, Bikbov, Mukharram, Park, Ki Ho, Cha, Soon Cheol, Yamashiro, Kenji, Zenteno, Juan C, Jonas, Jost B, Kumar, Rajesh S, Perera, Shamira A, Chan, Anita S Y, Kobakhidze, Nino, George, Ronnie, Vijaya, Lingam, Do, Tan, Edward, Deepak P, de Juan Marcos, Lourdes, Pakravan, Mohammad, Moghimi, Sasan, Ideta, Ryuichi, Bach-Holm, Daniella, Kappelgaard, Per, Wirostko, Barbara, Thomas, Samuel, Gaston, Daniel, Bedard, Karen, Greer, Wenda L, Yang, Zhenglin, Chen, Xueyi, Huang, Lulin, Sang, Jinghong, Jia, Hongyan, Jia, Liyun, Qiao, Chunyan, Zhang, Hui, Liu, Xuyang, Zhao, Bowen, Wang, Ya-Xing, Xu, Liang, Leruez, Stéphanie, Reynier, Pascal, Chichua, George, Tabagari, Sergo, Uebe, Steffen, Zenkel, Matthias, Berner, Daniel, Mossböck, Georg, Weisschuh, Nicole, Hoja, Ursula, Welge-Luessen, Ulrich-Christoph, Mardin, Christian, Founti, Panayiota, Chatzikyriakidou, Anthi, Pappas, Theofanis, Anastasopoulos, Eleftherios, Lambropoulos, Alexandros, Ghosh, Arkasubhra, Shetty, Rohit, Porporato, Natalia, Saravanan, Vijayan, Venkatesh, Rengaraj, Shivkumar, Chandrashekaran, Kalpana, Narendran, Sarangapani, Sripriya, Kanavi, Mozhgan R, Beni, Afsaneh Naderi, Yazdani, Shahin, lashay, Alireza, Naderifar, Homa, Khatibi, Nassim, Fea, Antonio, Lavia, Carlo, Dallorto, Laura, Rolle, Teresa, Frezzotti, Paolo, Paoli, Daniela, Salvi, Erika, Manunta, Paolo, Mori, Yosai, Miyata, Kazunori, Higashide, Tomomi, Chihara, Etsuo, Ishiko, Satoshi, Yoshida, Akitoshi, Yanagi, Masahide, Kiuchi, Yoshiaki, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Aihara, Makoto, Inatani, Masaru, Miyake, Masahiro, Gotoh, Norimoto, Matsuda, Fumihiko, Yoshimura, Nagahisa, Ikeda, Yoko, Ueno, Morio, Sotozono, Chie, Jeoung, Jin Wook, Sagong, Min, Park, Kyu Hyung, Ahn, Jeeyun, Cruz-Aguilar, Marisa, Ezzouhairi, Sidi M, Rafei, Abderrahman, Chong, Yaan Fun, Ng, Xiao Yu, Goh, Shuang Ru, Chen, Yueming, Yong, Victor H K, Khan, Muhammad Imran, Olawoye, Olusola O, Ashaye, Adeyinka O, Ugbede, Idakwo, Onakoya, Adeola, Kizor-Akaraiwe, Nkiru, Teekhasaenee, Chaiwat, Suwan, Yanin, Supakontanasan, Wasu, Okeke, Suhanya, Uche, Nkechi J, Asimadu, Ifeoma, Ayub, Humaira, Akhtar, Farah, Kosior-Jarecka, Ewa, Lukasik, Urszula, Lischinsky, Ignacio, Castro, Vania, Grossmann, Rodolfo Perez, Megevand, Gordana Sunaric, Roy, Sylvain, Dervan, Edward, Silke, Eoin, Rao, Aparna, Sahay, Priti, Fornero, Pablo, Cuello, Osvaldo, Sivori, Delia, Zompa, Tamara, Mills, Richard A, Souzeau, Emmanuelle, Mitchell, Paul, Wang, Jie Jin, Hewitt, Alex W, Coote, Michael, Crowston, Jonathan G, Astakhov, Sergei Y, Akopov, Eugeny L, Emelyanov, Anton, Vysochinskaya, Vera, Kazakbaeva, Gyulli, Fayzrakhmanov, Rinat, Al-Obeidan, Saleh A, Owaidhah, Ohoud, Aljasim, Leyla Ali, Chowbay, Balram, Foo, Jia Nee, Soh, Raphael Q, Sim, Kar Seng, Xie, Zhicheng, Cheong, Augustine W O, Mok, Shi Qi, Soo, Hui Meng, Chen, Xiao Yin, Peh, Su Qin, Heng, Khai Koon, Husain, Rahat, Ho, Su-Ling, Hillmer, Axel M, Cheng, Ching-Yu, Escudero-Domínguez, Francisco A, González-Sarmiento, Rogelio, Martinon-Torres, Frederico, Salas, Antonio, Pathanapitoon, Kessara, Hansapinyo, Linda, Wanichwecharugruang, Boonsong, Kitnarong, Naris, Sakuntabhai, Anavaj, Nguyn, Hip X, Nguyn, Giang T T, Nguyn, Trình V, Zenz, Werner, Binder, Alexander, Klobassa, Daniela S, Hibberd, Martin L, Davila, Sonia, Herms, Stefan, Nöthen, Markus M, Moebus, Susanne, Rautenbach, Robyn M, Ziskind, Ari, Carmichael, Trevor R, Ramsay, Michele, Álvarez, Lydia, García, Montserrat, González-Iglesias, Héctor, Rodríguez-Calvo, Pedro P, Cueto, Luis Fernández-Vega, Oguz, Çilingir, Tamcelik, Nevbahar, Atalay, Eray, Batu, Bilge, Aktas, Dilek, Kasım, Burcu, Wilson, M Roy, Coleman, Anne L, Liu, Yutao, Challa, Pratap, Herndon, Leon, Kuchtey, Rachel W, Kuchtey, John, Curtin, Karen, Chaya, Craig J, Crandall, Alan, Zangwill, Linda M, Wong, Tien Yin, Nakano, Masakazu, Kinoshita, Shigeru, den Hollander, Anneke I, Vesti, Eija, Fingert, John H, Lee, Richard K, Sit, Arthur J, Shingleton, Bradford J, Wang, Ningli, Cusi, Daniele, Qamar, Raheel, Kraft, Peter, Pericak-Vance, Margaret A, Raychaudhuri, Soumya, Heegaard, Steffen, Kivelä, Tero, Reis, André, Kruse, Friedrich E, Weinreb, Robert N, Pasquale, Louis R, Haines, Jonathan L, Thorsteinsdottir, Unnur, Jonasson, Fridbert, Allingham, R Rand, Milea, Dan, Ritch, Robert, Kubota, Toshiaki, Tashiro, Kei, Vithana, Eranga N, Micheal, Shazia, Topouzis, Fotis, Craig, Jamie E, Dubina, Michael, Sundaresan, Periasamy, Stefansson, Kari, Wiggs, Janey L, Pasutto, Francesca, and Khor, Chiea Chuen
- Abstract
Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10−14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
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- 2017
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23. Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies
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Lasserre, Jean-Paul, Dautant, Alain, Aiyar, Raeka S., Kucharczyk, Roza, Glatigny, Annie, Tribouillard-Tanvier, Déborah, Rytka, Joanna, Blondel, Marc, Skoczen, Natalia, Reynier, Pascal, Pitayu, Laras, Rötig, Agnès, Delahodde, Agnès, Steinmetz, Lars M., Dujardin, Geneviève, Procaccio, Vincent, and di Rago, Jean-Paul
- Abstract
Mitochondrial diseases are severe and largely untreatable. Owing to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. Much of our current understanding of mitochondrial function and dysfunction comes from studies in the baker's yeast Saccharomyces cerevisiae. Because of its good fermenting capacity, S. cerevisiae can survive mutations that inactivate oxidative phosphorylation, has the ability to tolerate the complete loss of mitochondrial DNA (a property referred to as ‘petite-positivity’), and is amenable to mitochondrial and nuclear genome manipulation. These attributes make it an excellent model system for studying and resolving the molecular basis of numerous mitochondrial diseases. Here, we review the invaluable insights this model organism has yielded about diseases caused by mitochondrial dysfunction, which ranges from primary defects in oxidative phosphorylation to metabolic disorders, as well as dysfunctions in maintaining the genome or in the dynamics of mitochondria. Owing to the high level of functional conservation between yeast and human mitochondrial genes, several yeast species have been instrumental in revealing the molecular mechanisms of pathogenic human mitochondrial gene mutations. Importantly, such insights have pointed to potential therapeutic targets, as have genetic and chemical screens using yeast.
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- 2015
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24. A Mitochondria-Specific Isoform of FASTK Is Present In Mitochondrial RNA Granules and Regulates Gene Expression and Function
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Jourdain, Alexis A., Koppen, Mirko, Rodley, Christopher D., Maundrell, Kinsey, Gueguen, Naïg, Reynier, Pascal, Guaras, Adela M., Enriquez, José A., Anderson, Paul, Simarro, Maria, and Martinou, Jean-Claude
- Abstract
The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause mitochondrial genetic diseases in humans. Here, we report that a novel translational variant of Fas-activated serine/threonine kinase (FASTK) co-localizes with mitochondrial RNA granules and is required for the biogenesis of ND6 mRNA, a mitochondrial-encoded subunit of the NADH dehydrogenase complex (complex I). We show that ablating FASTK expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo. FASTK binds at multiple sites along the ND6 mRNA and its precursors and cooperates with the mitochondrial degradosome to ensure regulated ND6 mRNA biogenesis. These data provide insights into the mechanism and control of mitochondrial RNA processing within mitochondrial RNA granules.
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- 2015
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25. Cataract as a Phenotypic Marker for a Mutation in WFS1, the Wolfram Syndrome Gene
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Cherif Titah, Salah Mohamed, Meunier, Isabelle, Blanchet, Catherine, Lopez, Severine, Rondouin, Gerard, Lenaers, Guy, Amati-Bonneau, Patrizia, Reynier, Pascal, Paquis-Flucklinger, Veronique, and Hamel, Christian P.
- Abstract
Purpose Wolfram syndrome (WS) or diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) (OMIM 222300) is an inherited neurodegenerative disease characterized by diabetes mellitus and optic atrophy as the 2 major criteria, followed later in life by deafness, diabetes insipidus, and various signs of neurologic impairment. The presence of a cataract has been variably mentioned in WS.Method Two members of a family had thorough ophthalmic examination and their DNA was screened for mutations in mitochondrial DNA, WFS1, OPA1, and OPA3 genes.Results We report a patient who first had surgery for bilateral cataract at age 5 and who subsequently presented typical signs of WS, i.e., diabetes mellitus, optic atrophy with reduced visual acuity at 20/400 on both eyes at age 22, and mild deafness. The patient was found to be a compound heterozygote for 2 truncating mutations in WFS1, the major WS gene. She carried the previously reported c.1231_1233 delCT and a novel c.2431_2465dup35 mutation. She also was heterozygote for a novel OPA1 sequence variant, c.929A>G in exon 9, whose pathogenicity remains uncertain. The patient's mother was a heterozygous carrier of the c.2431_2465dup35 mutation. She did not have diabetes mellitus or optic atrophy but had bilateral polar cataract. She did not carry the OPA1 sequence variant.Conclusions Cataract could be a marker for the WFS1 heterozygosity in this family, namely the c.2431_2465dup35 mutation.
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- 2012
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26. De la levure aux maladies neurodégénératives
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Lenaers, Guy, Amati-Bonneau, Patrizia, Delettre, Cécile, Chevrollier, Arnaud, Verny, Christophe, Miléa, Dan, Procaccio, Vincent, Bonneau, Dominique, Hamel, Christian, and Reynier, Pascal
- Abstract
L’identification, il y a dix ans, d’altérations de la dynamique mitochondriale dans des maladies neurodégénératives héréditaires affectant principalement les nerfs optiques et périphériques a signé l’émergence d’un nouveau type de mécanisme physiopathologique responsable de mitochondriopathies. Celui-ci implique des mutations dans les gènes codant des GTPases de la famille des dynamines qui assurent la fusion ou la fission du réseau mitochondrial. Des altérations similaires de la dynamique mitochondriale ont aussi été récemment retrouvées dans les maladies d’Alzheimer et de Parkinson, soulignant le rôle essentiel joué par la plasticité mitochondriale dans la survie neuronale, par le contrôle de l’activité énergétique et de sa distribution le long des axones.
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- 2010
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27. Genetically determined optic neuropathies
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Milea, Dan, Amati-Bonneau, Patrizia, Reynier, Pascal, and Bonneau, Dominique
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The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.
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- 2010
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28. Abstract 10948: Post-Infarct Cardiac Remodeling Predictions with Machine Learning
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Dieu, Xavier, Chabrun, Floris, PRUNIER, FABRICE, Reynier, Pascal, Furber, Alain p, Garcia, Gabriel, Bière, Loïc, and Mirebeau-Prunier, Delphine
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Introduction:We sought to improve the risk prediction of 3-month left ventricular remodeling (LVR) occurrence after myocardial infarction (MI), using a state-of-the-art machine learning approach.Methods:We retrieved 135 variables, ranging from clinical, biological and cardiac magnetic resonance data, from 379 patients with ST-elevated myocardial infarction and processed them with a machine learning pipeline using advanced feature selection and modelling algorithms such as gradient boosting, neural networks or recurrent neural networks.Results:A baseline logistic regression model using known variables such as infarct size, creatine kinase peak, no reflow and cardiovascular risk factors, achieved an AUC of 0.71 on the test, with 67% sensitivity and 64 % specificity. In comparison, our best predictive model was a neural network using seven variables (in order of importance): creatine kinase, mean corpuscular volume, baseline left atrial surface, history of diabetes, history of hypertension, red blood cell distribution width, and creatinine. This model achieved an AUC of 0.78 on the test set, reaching a sensitivity of 92% and a specificity of 67%, outperforming the baseline model.Conclusions:We were able to achieve state-of-the-art performance with a high level of sensitivity for the prediction of a 3-month post-MI LVR. Our unbiased data-driven machine learning approach highlights the role of classical parameters alongside unexpected variables such as left atrial dilation at baseline, mean corpuscular volume and red blood cell distribution width whose role in the pathophysiology of post-MI cardiac remodeling remain to be clarified. The relative simplicity and the good availability of these parameters make our new approach suitable for clinical testing.
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- 2021
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29. OPA1 R445H mutation in optic atrophy associated with sensorineural deafness
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Amati‐Bonneau, Patrizia, Guichet, Agnès, Olichon, Aurélien, Chevrollier, Arnaud, Viala, Frédérique, Miot, Stéphanie, Ayuso, Carmen, Odent, Sylvie, Arrouet, Catherine, Verny, Christophe, Calmels, Marie‐Noelle, Simard, Gilles, Belenguer, Pascale, Wang, Jing, Puel, Jean‐Luc, Hamel, Christian, Malthièry, Yves, Bonneau, Dominique, Lenaers, Guy, and Reynier, Pascal
- Abstract
The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy. Skin fibroblasts showed hyperfragmentation of the mitochondrial network, decreased mitochondrial membrane potential, and adenosine triphosphate synthesis defect. In addition, OPA1 was found to be widely expressed in the sensory and neural cochlear cells of the guinea pig. Thus, optic atrophy and deafness may be related to energy defects due to a fragmented mitochondrial network. Ann Neurol 2005
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- 2005
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30. Mitochondries et reproduction
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May-Panloup, Pascale, Chrétien, Marie-Françoise, Malthièry, Yves, and Reynier, Pascal
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Les mitochondries jouent un rôle central dans le métabolisme énergétique cellulaire. Une de leurs particularités est de posséder leur propre génome, dont la transmission est exclusivement maternelle. Leur implication dans la reproduction humaine est une notion relativement récente qui suscite un intérêt scientifique et médical croissant. Elles peuvent influencer la qualité des ovocytes et des spermatozoïdes, mais aussi la fécondation et le développement embryonnaire. De nouvelles techniques thérapeutiques telles que le transfert de cytoplasme ovocytaire compromettent fortement la transmission uniparentale de l’ADN mitochondrial et soulèvent d’importantes questions éthiques. Cet article tente de faire le point sur les acquisitions récentes concernant le rôle des mitochondries dans la fertilité et la reproduction humaines.
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- 2004
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31. Leigh‐like encephalopathy complicating Leber's hereditary optic neuropathy
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Funalot, Benoît, Reynier, Pascal, Vighetto, Alain, Ranoux, Danièle, Bonnefont, Jean‐Paul, Godinot, Catherine, Malthièry, Yves, and Mas, Jean‐Louis
- Abstract
Leber's hereditary optic neuropathy is a mitochondrial disease caused by point mutations in mitochondrial DNA. It usually presents as severe bilateral visual loss in young adults. We report on a neurological disorder resembling Leigh syndrome, which complicated Leber's hereditary optic neuropathy in three unrelated male patients harboring mitochondrial DNA mutations at nucleotide positions 3460, 14459, and 14484, respectively. This Leigh‐like encephalopathy appears to be associated with a much more severe outcome than isolated Leber's hereditary optic neuropathy.
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- 2002
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32. A Conserved N-Terminal Sequence Targets Human DAP3 to Mitochondria
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Morgan, Catherine J., Jacques, Caroline, Savagner, Fre´de´rique, Tourmen, Yves, Mirebeau, Delphine P., Malthie`ry, Yves, and Reynier, Pascal
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Human DAP3 (death-associated protein-3) has been identified as an essential positive mediator of programmed cell death. Structure–function studies have shown previously the N-terminal extremity of the protein to be required in apoptosis induction. Analysis of human DAP3 gene structure predicted 13 exons and subsequent targeting prediction by two software packages (MITOPROT and TargetP) gave a high probability for mitochondrial targeting. The predicted N-terminal targeting structure was also found in the mouse, Drosophila, and C. elegans orthologues with a strong sequence homology between mouse and human. Secondary structure analyses identified α-helical structures typical of mitochondrial target peptides. To confirm experimentally this targeting we constructed a fusion protein with N-terminal human DAP3 upstream of enhanced green fluorescent protein (EGFP). Confocal analysis of transfected human fibroblasts clearly demonstrated EGFP localization exclusive to mitochondria. The positioning of this key apoptotic factor at the heart of the mitochondrial pathway provides exciting insight into its role in programmed cell death.
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- 2001
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33. Long PCR Analysis of Human Gamete mtDNA Suggests Defective Mitochondrial Maintenance in Spermatozoa and Supports the Bottleneck Theory for Oocytes
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Reynier, Pascal, Chrétien, Marie-Françoise, Savagner, Frédérique, Larcher, Gérald, Rohmer, Vincent, Barrière, Paul, and Malthièry, Yves
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The long PCR and the Southern blot techniques were used to study mitochondrial DNA (mtDNA) in 94 sperm samples, and in 35 oocytes collected from 12 women. The sperm samples were classified in two sets: 37 samples from normal subjects, and 57 samples from patients with oligoasthenospermia. In both sets, most of the spermatozoan mitochondria had multiple mtDNA deletions. The rate of mtDNA mutation, which appears unexpectedly high, considering the short life span of the spermatozoa, may be due to impaired maintenance during differentiation. In contrast, despite the long life span of oocytes and the extended meiotic period, oocyte mitochondria showed few mtDNA rearrangements. However, mitochondria in oocytes from a given donor revealed considerable mutational heterogeneity. This supports the bottleneck theory of rapid segregation of mtDNA genotypes during early oogenesis. The long PCR technique, which allows analysis of the entire mitochondrial genome, provides new information on mtDNA instability in human gametes. Our findings suggest that mtDNA maintenance differs in the two types of gametes.
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- 1998
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34. Cloning and initial characterization of human and mouse Spot 14 genes 1
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Grillasca, Joël-Paul, Gastaldi, Marguerite, Khiri, Hacène, Dace, Alexandra, Peyrol, Nicole, Reynier, Pascal, Torresani, Janine, and Planells, Richard
- Abstract
The intricate regulation of Spot 14 expression in rat lipogenic tissues has provided a useful tool in studying nutritional and hormonal factors involved in transcription. To gain insight into its function and its possible involvement in human lipid disorders, we cloned human and mouse Spot 14 genes that shared with the rat gene a strong homology concerning the deduced amino acid sequence (81 and 94%, respectively) as well as the promoter region. The mouse promoter was characterized by transfection studies, while quantitative RT‐PCR and in situ hybridization experiments showed that Spot 14 is expressed in human liver and, at a high level, in multiple symmetric lipomatosis nodules.
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- 1997
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35. Quantitative multistandard RT-PCR assay using interspecies polymorphism
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Khiri, Hace`ne, Reynier, Pascal, Peyrol, Nicole, Lerique, Brice, Torresani, Janine, and Planells, Richard
- Abstract
The use of RT-PCR to quantify mRNA is often compromised by the variability of reverse-transcription and amplification reactions as well as by the difficulty of assessing the amount and/or the integrity of input RNA. Use of a competitor RNA or the coamplification of an endogenous standard are widespread methods of monitoring these steps. Taking advantage of both sequence conservation between homologous genes in related animal species and interspecific polymorphism, a protocol that may be regarded as a compromise between these two methods is described here. Total RNA samples, extracted from even minute amounts of tissue belonging to a first animal species, were supplemented with a constant amount of total RNA prepared from a second animal species, which thus acts as a multistandard source. The mixture was reverse-transcribed using hexa-random primers. Separate PCRs were then undertaken so that, for each mRNA of interest, products from both origins could be distinguished. Since the ratio between amplified mRNAs is constant in the standard preparation, an accurate normalization in the assay samples of most variations inherent to PCR is obtained. This protocol allows quantification of several mRNAs species, whose amounts may be very different, in a single cDNA preparation.
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- 1996
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36. Cloning and initial characterization of human and mouse Spot 14 genes 1Nucleotide sequences of the Mus musculusand Homo sapiensSpot 14 genes have been submitted to the EMBL Data Bank under the accession numbers X95279 and Y08409, respectively. 1
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Grillasca, Joël-Paul, Gastaldi, Marguerite, Khiri, Hacène, Dace, Alexandra, Peyrol, Nicole, Reynier, Pascal, Torresani, Janine, and Planells, Richard
- Abstract
The intricate regulation of Spot 14 expression in rat lipogenic tissues has provided a useful tool in studying nutritional and hormonal factors involved in transcription. To gain insight into its function and its possible involvement in human lipid disorders, we cloned human and mouse Spot 14 genes that shared with the rat gene a strong homology concerning the deduced amino acid sequence (81 and 94%, respectively) as well as the promoter region. The mouse promoter was characterized by transfection studies, while quantitative RT-PCR and in situ hybridization experiments showed that Spot 14 is expressed in human liver and, at a high level, in multiple symmetric lipomatosis nodules.
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- 1997
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37. The cytokine profile of follicular fluid changes during ovarian ageing
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Bouet, Pierre-Emmanuel, Boueilh, Thomas, de la Barca, Juan Manuel Chao, Boucret, Lisa, Blanchard, Simon, Ferré-L’Hotellier, Véronique, Jeannin, Pascale, Descamps, Philippe, Procaccio, Vincent, Reynier, Pascal, and May-Panloup, Pascale
- Abstract
Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing.
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- 2020
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38. 0059 : The involvement of a cocktail of amino acids in remote ischemic preconditioning induced cardioprotection in acute myocardial infarction.
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Bakhta, Oussama, De La Barca, Juan Manuel Chao, Mirebeau-Prunier, Delphine, Tamareille, Sophie, Simard, Gilles, Gadras, Cédric, Reynier, Pascal, and Prunier, Fabrice
- Abstract
Background Remote ischemic preconditionning (RIPC) has emerged as an attractive therapeutic procedure to protect the heart against ischemia/reperfusion (I/R) injury. Despite strong evidences of the critical role played by circulating humoral mediators for signal transduction, their identities still remain unknown. Using a targeted metabolomic approach we previously identified Glycine (GLY) and Kynurenine (KYN) as potential mediators for RIPC induced cardioprotection in both rats and humans. Aim of the study this study sought to determine whether a treatment with GLY and KYN alone or in combination could mimic the cardioprotective effect of the RIPC. Methods Male Wistar rats, 8-10 weeks exposed to myocardial I/R were allocated to one of the following six groups: Myocardial Infarction (MI) , rats were subjected to myocardial I/R without any further intervention; RIPC+MI , four cycles of limb I/R were applied prior to the myocardial ischemia; Metabolites+ MI , with intraperitoneal (ip) injection of a combined GLY (0.5mg/g body weight) and KYN (0.3 mg/g body weight) 10 min before MI; Vehicle+MI , with ip injection of the vehicle 10 min before MI; GLY+MI , with ip injection of single dose of GLY 10 min before MI; and KYN+MI , with an ip injection of single dose of KYN 10 min prior to MI. Hearts were excised after 2h of reperfusion, the area at risk (AAR) and infarct size (AN) were measured after TTC staining. GLY and KYN plasma concentrations were determined by mass spectroscopy LC-MS/MS at 3 points of time: 15, 30 and 45 min after the ip injection. Results The metabolites blood assay showed a significant increase of both glycine and kynurenine in blood plasma 15 min after the intraperitoneal injection with a peak at 30 min. As compared to MI , both RIPC+MI and Metabolites+MI exhibited a smaller infarct size (AN/AAR=39.59±3.76% for Vehicle+MI vs. 27.15±4.47% for the Metabolites+MI group, and 42.49±2.42% for MI vs. 34.53±2.28% for the RIPC+MI , both p <0.05). Kynurenine injection alone and Glycine injection alone significantly decreased infarct size (AN/AAR=27.70±2.53% in Kynurenine+MI vs. MI group; p =0.0018 and 33.24±2.30% in Glycine+MI , vs. MI, p=0.006 ). Conclusion We report that RIPC-induced cardioprotection may involve a cocktail of amino acids for signal transduction from the remote organ to the myocardium. The author hereby declares no conflict of interest [ABSTRACT FROM AUTHOR]
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- 2016
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39. Mitochondrial DNA in the Oocyte and the Developing Embryo.
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May-Panloup, Pascale, Chretien, Marie-Françoise, Malthiery, Yves, and Reynier, Pascal
- Subjects
MITOCHONDRIAL DNA - Abstract
An abstract of the article "Mitochondrial DNA in the Oocyte and the Developing Embryo," by Pascale May-Panloup and colleagues is presented.
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- 2007
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