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201. Pharmacodynamic effects of cinacalcet after kidney transplantation: once- versus twice-daily dose

Author: Luciana Spataru, Laurence Lavayssière, Nassim Kamar, Lionel Rostaing, Dominique Durand, Laure Esposito, Isabelle Gennero, Olivier Cointault, Joelle Guitard, Peggy Gandia, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Pharmacocinétique et de Toxicologie [CHU Toulouse], and Simon, Marie Francoise
Subjects: Male, Cinacalcet, 030232 urology & nephrology, Parathyroid hormone, 030204 cardiovascular system & hematology, MESH: Cyclosporine, MESH: Kidney Transplantation, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Longitudinal Studies, Prospective Studies, MESH: Longitudinal Studies, MESH: Phosphorus, Kidney transplantation, MESH: Aged, MESH: Middle Aged, Phosphorus, MESH: Naphthalenes, Middle Aged, MESH: Hyperparathyroidism, Secondary, 3. Good health, MESH: Parathyroid Hormone, Parathyroid Hormone, Nephrology, MESH: Kidney Failure, Chronic, MESH: Calcium, Cyclosporine, Female, medicine.drug, Adult, medicine.medical_specialty, Hypercalcaemia, Urology, Renal function, Naphthalenes, Tacrolimus, MESH: Hypercalcemia, 03 medical and health sciences, Internal medicine, medicine, MESH: Tacrolimus, Humans, Aged, Calcium metabolism, Transplantation, Hyperparathyroidism, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Adult, medicine.disease, Kidney Transplantation, MESH: Male, MESH: Prospective Studies, Endocrinology, Hypercalcemia, Kidney Failure, Chronic, Calcium, Hyperparathyroidism, Secondary, business, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d. METHODS: Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period. RESULTS: During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function. CONCLUSION: Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.
Published: 2008

202. Production of branched-chain aroma compounds by Propionibacterium freudenreichii: links with the biosynthesis of membrane fatty acids

Author: Julien Dherbécourt, Marie-Bernadette Maillard, Anne Thierry, D. Catheline, UMR1253, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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 la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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), Laboratoire de Biochimie et Nutrition Humaine, AGROCAMPUS OUEST, Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, and Laboratoire de Biochimie
Subjects: MESH: Bacteriological Techniques, Applied Microbiology and Biotechnology, n-3, chemistry.chemical_compound, Cheese, animal, MESH: Animals, membrane, chemistry.chemical_classification, bactérie, 0303 health sciences, Growth medium, biology, Propionibacterium freudenreichii, Fatty Acids, desaturation, General Medicine, bacterium, arôme, Amino acid, MESH: Fatty Acids, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, dairy product, MESH: Propionibacterium, Swiss cheese, FATTY ACID, Leucine, Biotechnology, composé volatil, cloning, produit laitier, 03 medical and health sciences, Biosynthesis, Valine, expression, Animals, Humans, FADS2, saturated fatty acids, MESH: Food Microbiology, 030304 developmental biology, human delta-5, Bacteriological Techniques, MESH: Humans, 030306 microbiology, Cell Membrane, Propionibacterium, AROMA COMPOUNDS, fatty-acids, biology.organism_classification, propionic acid bacteria, MESH: Cheese, MESH: Leucine, chemistry, Food Microbiology, PROPIONIBACTERIUM FREUDENREICHII, bactérie propionique, Isoleucine, desaturase, Amino Acids, Branched-Chain, MESH: Amino Acids, Branched-Chain, MESH: Cell Membrane
Abstract: Aims: Short branched-chain fatty acids (BCFAs) are cheese flavour compounds, which result from the conversion of branched-chain amino acids (BCAAs). In Swiss cheese, the production of short BCFAs is mainly performed by Propionibacterium freudenreichii and is strain dependent. Our aim was to investigate the possible links between the biosynthesis of short BCFAs and membrane BCFAs in P. freudenreichii. Methods and Results: Short and membrane BCFAs were analysed by gas chromatography- mass spectrometry. Two strains differing in their capacities to release short BCFAs were selected. Tri-deuterated-labelled leucine was used in both strains as a precursor of short extracellular iso-BCFAs and of membrane iso-BCFAs. The proportions of anteiso : iso BCFAs synthesized varied as function of the BCAAs provided in the growth medium, from 72 : 28 to 100 : 0, with leucine and valine, and with isoleucine as sole BC precursors, respectively. The branching pattern of short BCFAs exactly matched that of membrane BCFAs, whatever the exogenous BCAAs provided. Conclusions: The biosynthesis of short BCFAs is closely related to that of membrane BCFAs in P. freudenreichii. Significance and Impact of the Study: The biosynthesis of short BCFAs in P. freudenreichii depends more on the strain than on the presence of exogenous BC precursors.
Published: 2008

203. Kind or quantity of lipids, is there such a thing as the omega-3 effect ?

Author: Weill, P., Mourot, Jacques, Schmitt, B., Kerhoas, N., Legrand, P., Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Centre d'Economie et de Sociologie Rurales Appliquées à l'Agriculture et aux Espaces Ruraux (CESAER), Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Biochimie et Nutrition Humaine, AGROCAMPUS OUEST, Valorex SAS, Systèmes d'élevage, nutrition animale et humaine (SENAH), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre d'Enseignement et de Recherche en Nutrition Humaine (CERNh), Association Bleu-Blanc-Coeur, Laboratoire de biochimie, Institut National de la Recherche Agronomique (INRA), Ecole Nationale Supérieure Agronomique de Rennes, Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA), and 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 la Recherche Agronomique (INRA)
Subjects: OBESITE, Alimentation humaine, [SDV]Life Sciences [q-bio], ETAT NUTRITIONNEL, ACIDE GRAS INSATURE, MACRONUTRIMENT, LIPIDE, ACIDE GRAS, [INFO]Computer Science [cs], NUTRITION, OMEGA 3, TROUBLE DE LA NUTRITION, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS, ACIDE GRAS n-3, OMEGA 6
Abstract: Nature ou quantité des lipides, l'effet des oméga-3 existe t-il?
Published: 2008

204. Isolation, characterization and molecular cloning of new temporins from the skin of the North African ranid Pelophylax saharicastar

Author: Abbassi, F., Oury, B., Blasco, T., Sereno, D., Bolbach, G., Nicolas, P., Hani, K., Mohamed, Amichea, Ladram, A., Peptidome de la Peau des Amphibiens (FRE 2852), Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Biochimie, Faculté de Médecine de Sousse, 4002 Sousse, Tunisia, Faculté de médecine de Sousse [Ibn EL Jazzar], Spectrométrie de Masse et Protéomique [IBPS] (IBPS-SPM), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie, and Sorbonne Université (SU)
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

205. Effects of TCF7L2 polymorphisms on obesity in European populations

Author: Michel Marre, Fritz F. Horber, Katrine Grau, David Meyre, Alex Duval, Christian Dina, Christine Proença, Hélène Choquet, Guillaume Charpentier, Thorkild I. A. Sørensen, Stéphane Cauchi, Philippe Froguel, Ruth Gutierrez-Aguilar, Beverley Balkau, Dominique Langin, Frédéric Capel, Natascha Potoczna, Simon, Marie Francoise, Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Preventive Medicine, Copenhagen University Hospital, Instabilité des microsatellites et cancers [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Déterminants génétiques du diabète de type 2 et de ses complications vasculaires ((U 695)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Obesity Centre, Klinik Lindberg, Obesity Center Klink Lindberg, Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de Corbeil, Genomic Medicine, Imperial College London-Hammersmith Hospital, Medical Research Council G0600331, Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Instabilité des microsatellites et cancers [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], and Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, endocrine system diseases, Polymorphism, Single Nucleotide/*genetics, Endocrinology, Diabetes and Metabolism, TCF Transcription Factors/*genetics/metabolism, Medicine (miscellaneous), Adipose tissue, Type 2 diabetes, Body Mass Index, 0302 clinical medicine, Endocrinology, Risk Factors, MESH: Risk Factors, Medicine, MESH: Obesity, MESH: Aged, 0303 health sciences, education.field_of_study, Nutrition and Dietetics, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: European Continental Ancestry Group, Middle Aged, MESH: Case-Control Studies, Pedigree, Diabetes Mellitus, Type 2/ethnology/etiology, Female, France, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, MESH: Diabetes Mellitus, Type 2, Adult, medicine.medical_specialty, endocrine system, MESH: Pedigree, Population, Subcutaneous Fat, Genetic Predisposition to Disease/ethnology/genetics, 030209 endocrinology & metabolism, Polymorphism, Single Nucleotide, White People, MESH: Body Mass Index, 03 medical and health sciences, MESH: Subcutaneous Fat, Internal medicine, Humans, Genetic Predisposition to Disease, Obesity, Allele, education, Alleles, 030304 developmental biology, Aged, MESH: Humans, business.industry, MESH: Alleles, Case-control study, nutritional and metabolic diseases, Obesity/complications/ethnology/*genetics, MESH: Adult, Odds ratio, medicine.disease, MESH: Male, European Continental Ancestry Group/ethnology/genetics, MESH: France, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, Case-Control Studies, business, TCF7L2, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: TCF Transcription Factors, Subcutaneous Fat/metabolism
Abstract: 1930-7381 (Print) Journal Article Research Support, Non-U.S. Gov't; International audience; The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele was previously associated with type 2 diabetes (T2D) and decreased BMI whereas haplotypes carrying the rs7903146 C and rs10885406 A alleles (HapA) were associated with increased BMI. The functional relevance of TCF7L2 polymorphisms and their effects on T2D and obesity remained to be further investigated.In white European populations, we found that the rs7903146 T allele was more associated with T2D in 3,547 non-obese individuals (odds ratio (OR) = 1.88 (1.69-2.10)) than in 1,110 class III obese subjects (OR = 1.24 (1.03-1.50)). No direct effect of the rs7903146 C allele and HapA was found on any form of obesity in 3,507 normal glucose tolerant (NGT) individuals, 1,106 pedigrees with familial obesity and 5,512 individuals from the French general population. However, in T2D subjects, the rs7903146 C allele was less prevalent in the 1,111 non-obese individuals (55.2%) compared to 659 class III obese subjects (67.5% OR = 1.69 (1.46-1.95)). Functional studies showed that the rs7903146 T allele is less prone to be bound by protein factors than the C allele in 3T3-L1, HepG2 and beta-TC3 cell lines and that TCF7L2 expression decreases in subcutaneous adipose tissue from NGT obese T/T carriers under calorie restriction.In conclusion, TCF7L2 is not a risk factor for obesity in European populations, but its effect on T2D risk is modulated by obesity. Furthermore, our data suggest that the rs7903146 T allele may be possibly functional and associated with a nominal decrease in TCF7L2 expression in adipose tissue of individuals under calorie restriction.
Published: 2008

206. PURE: A webserver for the prediction of domains in unassigned regions in proteins

Author: Khader Shameer, Chilamakuri Chandra Sekhar Reddy, Bernard Offmann, Ramanathan Sowdhamini, Laboratoire de Biochimie et Génétique Moléculaire (LBGM), Université de La Réunion (UR), National Centre for Biological Sciences (TIFR), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie et Génétique Moléculaire ( LBGM ), Université de la Réunion ( UR ), National Centre for Biological Sciences ( TIFR ), Dynamique des Structures et Interactions des Macromolécules Biologiques- Pôle de La Réunion ( DSIMB Réunion ), Dynamique des Structures et Interactions des Macromolécules Biologiques ( DSIMB ), and Institut National de la Transfusion Sanguine [Paris] ( INTS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Transfusion Sanguine [Paris] ( INTS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de la Réunion ( UR )
Subjects: Web server, Sequence analysis, Protein domain, Amino Acid Motifs, Pfam Domain, Mycoplasma gallisepticum, Context (language use), Computational biology, Biology, computer.software_genre, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Coiled Coil, Domain (software engineering), Pattern Recognition, Automated, 03 medical and health sciences, Protein structure, Structural Biology, Sequence Analysis, Protein, Animals, Cluster Analysis, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Databases, Protein, Protein secondary structure, lcsh:QH301-705.5, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Sequence (medicine), Genetics, 0303 health sciences, Sequence Segment, Applied Mathematics, 030302 biochemistry & molecular biology, Computational Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, Protein Structure, Tertiary, lcsh:Biology (General), Structural Homology, Protein, Transmembrane Region, lcsh:R858-859.7, computer, Software, Research Article, Adenylyl Cyclases, Query Sequence
Abstract: Background Protein domains are the structural and functional units of proteins. The ability to parse proteins into different domains is important for effective classification, understanding of protein structure, function, and evolution and is hence biologically relevant. Several computational methods are available to identify domains in the sequence. Domain finding algorithms often employ stringent thresholds to recognize sequence domains. Identification of additional domains can be tedious involving intense computation and manual intervention but can lead to better understanding of overall biological function. In this context, the problem of identifying new domains in the unassigned regions of a protein sequence assumes a crucial importance. Results We had earlier demonstrated that accumulation of domain information of sequence homologues can substantially aid prediction of new domains. In this paper, we propose a computationally intensive, multi-step bioinformatics protocol as a web server named as PURE (P rediction of U nassigned RE gions in proteins) for the detailed examination of stretches of unassigned regions in proteins. Query sequence is processed using different automated filtering steps based on length, presence of coiled-coil regions, transmembrane regions, homologous sequences and percentage of secondary structure content. Later, the filtered sequence segments and their sequence homologues are fed to PSI-BLAST, cd-hit and Hmmpfam. Data from the various programs are integrated and information regarding the probable domains predicted from the sequence is reported. Conclusion We have implemented PURE protocol as a web server for rapid and comprehensive analysis of unassigned regions in the proteins. This server integrates data from different programs and provides information about the domains encoded in the unassigned regions.
Published: 2008

207. Antiproliferative activities of resveratrol and related compounds in human hepatocyte derived HepG2 cells are associated with biochemical cell disturbance revealed by fluorescence analyses

Author: Brigitte Jannin, Jessica Abrossinow, Allan Lançon, Gérard Lizard, Edmond Kahn, Norbert Latruffe, Didier Colin, Dominique Delmas, Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: Antioxidant, endocrine system diseases, medicine.medical_treatment, Cell, 3-Viniferin, Resveratrol, Biochemistry, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Phenols, Acetate derivatives, Cell Line, Tumor, Stilbenes, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, skin and connective tissue diseases, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Cell Proliferation, Cell uptake, 0303 health sciences, Cell growth, organic chemicals, food and beverages, General Medicine, Free radical scavenger, 3. Good health, medicine.anatomical_structure, chemistry, Cell culture, Polyphenol, 030220 oncology & carcinogenesis, Cancer cell, Autofluorescence, Hepatocytes, NADP
Abstract: International audience; Resveratrol is a well known polyphenol largely produced in grapevine. It is a strong antioxidant and a free radical scavenger. It exhibits several beneficial effects for health including cancer. Resveratrol antioxidant activity is essential in the prevention of chemical-induced cancer by inhibiting initiation step of carcinogenesis process but it is also considered to inhibit cancer promotion and progression steps. While the effects of resveratrol on cancer cells are widely described, the data available on the antiproliferative potential of resveratrol derivatives remain weak. Nevertheless, resveratrol analogs could exhibit stronger potentials than the parent molecule. So, we compared the cellular effects of trans-resveratrol, trans-epsilon-viniferin and their respective acetate derivatives, as well as a polyphenol mixture extracted from grapevine shoots, called vineatrol. We studied their abilities to interfere with cell proliferation, their uptake and their effects on parameters of cellular state in human hepatoma cells (HepG2). Cell growth experiments show that resveratrol triacetate presents a slightly better antiproliferative potential than resveratrol. The dimer epsilon-viniferin,as well as its pentaacetate analog, is less powerful than resveratrol, although a similar uptake kinetics in cells. Interestingly, among the tested polyphenols, vineatrol is the most potent solution, indicating a possible synergistic effect of both resveratrol and epsilon-viniferin. We took advantage of the fluorescence properties of these compounds to evidence cellular uptake by using flow cytometry. In addition, by competition assay, we demonstrate that resveratrol triacetate enters in hepatic HepG2 cells by the same way as resveratrol. By autofluorescence in situ measurement we observed that resveratrol and related compounds induce deep changes in cells activity. These changes occur mainly by increasing NADPH cell content and the number of green fluorescent cytoplasmic granular structures which may be related to an induction of detoxifying enzyme mechanisms.
Published: 2007

208. The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human white adipocytes

Author: Mazzucotelli, Anne, Viguerie, Nathalie, Tiraby, Claire, Annicotte, Jean-Sébastien, Mairal, Aline, Klimcáková, Eva, Lepin, Emmanuelle, Delmar, Paul, Dejean, Sébastien, Tavernier, Geneviève, Lefort, Corinne, Hidalgo, Juan, Pineau, Thierry, Fajas, Lluis, Clément, Karine, Langin, Dominique, Laboratoire de Biochimie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil ( I2MR ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Métabolisme et cancer, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Mathématiques Appliquées aux Systèmes - EA 4037 ( MAS ), Ecole Centrale Paris, Statistics and Probality Laboratory, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Institute of Neurosciences, University of Barcelona, Pharmacology and Toxicology Laboratory, Institut National de la Recherche Agronomique ( INRA ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mathématiques Appliquées aux Systèmes - EA 4037 (MAS), Laboratoire de Statistique et Probabilités (LSP), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Enzymologic, MESH : PPAR gamma, [SDV]Life Sciences [q-bio], Nuclear Receptor Coactivators, MESH : PPAR alpha, MESH : Adipocytes, Gene Expression Regulation, Enzymologic, MESH : Gene Expression Regulation, Enzymologic, MESH : Intracellular Signaling Peptides and Proteins, Glycerol Kinase, MESH: Intracellular Signaling Peptides and Proteins, Adipocytes, Humans, PPAR alpha, MESH: PPAR alpha, MESH: Adipocytes, MESH : Glycerol Kinase, MESH: Humans, MESH : Gene Expression Regulation, MESH: Gene Expression Regulation, Enzymologic, MESH: Glycerol Kinase, MESH : Humans, Intracellular Signaling Peptides and Proteins, MESH: Gene Expression Regulation, [SDV] Life Sciences [q-bio], PPAR gamma, Gene Expression Regulation, MESH: PPAR gamma
Abstract: International audience; OBJECTIVE: The purpose of this work was to determine the pattern of genes regulated by peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha (PGC-1 alpha) in human adipocytes and the involvement of PPARalpha and PPARgamma in PGC-1 alpha transcriptional action. RESEARCH DESIGN AND METHODS: Primary cultures of human adipocytes were transduced with a PGC-1 alpha adenovirus and treated with PPARgamma and PPARalpha agonists. Variation in gene expression was assessed using pangenomic microarrays and quantitative RT-PCR. To investigate glycerol kinase (GyK), a target of PGC-1 alpha, we measured enzymatic activity and glycerol incorporation into triglycerides. In vivo studies were performed on wild-type and PPARalpha(-/-) mice. The GyK promoter was studied using chromatin immunoprecipitation and promoter reporter gene assays. RESULTS: Among the large number of genes regulated by PGC-1 alpha independently of PPARgamma, new targets involved in metabolism included the gene encoding GyK. The induction of GyK by PGC-1 alpha was observed at the levels of mRNA, enzymatic activity, and glycerol incorporation into triglycerides. PPARalpha was also upregulated by PGC-1 alpha. Its activation led to an increase in GyK expression and activity. PPARalpha was shown to bind and activate the GyK promoter. Experiments in mice confirmed the role of PGC-1 alpha and PPARalpha in the regulation of GyK in vivo. CONCLUSIONS: This work uncovers novel pathways regulated by PGC-1 alpha and reveals that PPARalpha controls gene expression in human white adipocytes. The induction of GyK by PGC-1 alpha and PPARalpha may promote a futile cycle of triglyceride hydrolysis and fatty acid reesterification.
Published: 2007

209. Regulation of inflammation-related genes in human adipose tissue

Author: Dominique Langin, Karine Clément, Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital de l'Hôtel-Dieu, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH: Inflammation, Panniculitis, Adipose tissue, MESH : Panniculitis, 0302 clinical medicine, Weight loss, Macrophage, Medicine, MESH: Obesity, MESH : Macrophages, MESH : Tumor Necrosis Factor-alpha, 0303 health sciences, MESH : Gene Expression Regulation, MESH: Panniculitis, MESH: Gene Expression Regulation, 3. Good health, Adipose Tissue, MESH : Obesity, medicine.symptom, Inflammation Mediators, MESH: Adipose Tissue, Calorie restriction, MESH: Inflammation Mediators, 030209 endocrinology & metabolism, Inflammation, Context (language use), Physical exercise, MESH : Adipose Tissue, MESH : Inflammation Mediators, 03 medical and health sciences, MESH: Gene Expression Profiling, Internal Medicine, Humans, Serum amyloid A, Obesity, 030304 developmental biology, MESH : Inflammation, MESH: Humans, business.industry, Tumor Necrosis Factor-alpha, MESH : Gene Expression Profiling, Gene Expression Profiling, Macrophages, MESH : Humans, MESH: Macrophages, Gene Expression Regulation, MESH: Tumor Necrosis Factor-alpha, Immunology, business
Abstract: International audience; The identification of a moderate increase in circulating inflammatory factors in obese subjects, the description of changes in inflammatory gene expression in adipose tissue (AT) and the discovery that macrophage cells infiltrate AT are observations contributing to the concept that human obesity is a chronic inflammatory illness. This concept has led to some revision of the physiopathology of obesity and of its related metabolic and cardiovascular co-morbidities. Low-grade inflammation in the AT and the subsequent production of specific biomarkers could actually link expanded fat mass to obesity complications. This review aims at providing an overview of the current knowledge brought up by human gene expression studies, notably those performed on a large scale in AT depots. The regulation of specific biomarkers related to inflammation and putative new candidates (i.e. cathepsins and serum amyloid A) is discussed in the context of weight loss programmes based on calorie restriction and physical exercise. The foreseen clinical and technological challenges are also summarized.
Published: 2007

210. Resistance to high-fat-diet-induced obesity and sexual dimorphism in the metabolic responses of transgenic mice with moderate uncoupling protein 3 overexpression in glycolytic skeletal muscles

Author: Jacques Rami, Geneviève Tavernier, Aline Mairal, François Crampes, Frédéric Capel, Jean A. Boutin, Claire Tiraby, C. Pujol, Dominique Langin, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Division de Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Blood Glucose, Male, RNA, Messenger/genetics, Endocrinology, Diabetes and Metabolism, Ion Channels, Mice, 0302 clinical medicine, Uncoupling Protein 3, Uncoupling protein, Glycolysis, MESH: Animals, Inner mitochondrial membrane, UCP3, 2. Zero hunger, Sex Characteristics, 0303 health sciences, MESH: Muscle, Skeletal, Mitochondrial Proteins/*genetics, MESH: Mitochondria, Muscle, MESH: Mitochondrial Proteins, MESH: Gene Expression Regulation, Mitochondria, Muscle/*physiology, MESH: Insulin Resistance, MESH: Dietary Fats, MESH: Glycolysis, Female, MESH: Sex Characteristics, Genetically modified mouse, medicine.medical_specialty, Ratón, MESH: Mice, Transgenic, Mice, Transgenic, Dietary Fats, Biology, Mitochondrial Proteins, 03 medical and health sciences, In vivo, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Internal Medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Muscle, Skeletal/*physiology, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, Insulin Resistance, MESH: Male, Mitochondria, Muscle, Ion Channels/*genetics, Sexual dimorphism, Endocrinology, Gene Expression Regulation, MESH: Ion Channels, MESH: Blood Glucose, Blood Glucose/*metabolism, MESH: Female, 030217 neurology & neurosurgery
Abstract: 0012-186X (Print) 0012-186X (Linking) Journal Article Research Support, Non-U.S. Gov't; International audience; AIMS/HYPOTHESIS: Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein expressed predominantly in glycolytic skeletal muscles. Its role in vivo remains poorly understood. The aim of the present work was to produce a mouse model with moderate overproduction and proper fibre-type distribution of UCP3. METHODS: Transgenic mice were created with a 16 kb region encompassing the human UCP3 gene. Mitochondrial uncoupling was investigated on permeabilised muscle fibres. Changes in body weight, adiposity and glucose or insulin tolerance were assessed in mice fed chow and high-fat diets. Indirect calorimetry was used to determine whole-body energy expenditure and substrate utilisation. RESULTS: Transgenic mice showed a twofold increase in UCP3 protein levels specifically in glycolytic muscles. Mitochondrial respiration revealed an increase of uncoupling in glycolytic but not in oxidative muscles. Transgenic mice gained less weight than wild-type littermates due to lower adipose tissue accretion when fed a high-fat diet. Animals showed a sexual dimorphism in metabolic responses. Female transgenic mice were more glucose-sensitive than wild-type animals, while male transgenic mice with high body weights had impaired glucose and insulin tolerance. Measurements of RQs in mice fed chow and high-fat diets suggested an impairment of metabolic flexibility in transgenic male mice. CONCLUSIONS/INTERPRETATION: Our data show that physiological overproduction of UCP3 in glycolytic muscles results in mitochondrial uncoupling, resistance to high-fat diet-induced obesity and sex specificity regarding insulin sensitivity and whole-body substrate utilisation.
Published: 2007

211. Differential display fingerprints: new approach to characterize smooth muscle cells and human coronary atherectomy tissues

Author: Francis Bayard, Yves Glock, François Heitz, Elizabeth Caussé, Meyer Elbaz, Nelly Blaes, Jacques Puel, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de cardiologie pédiatrique, Clinique Pasteur [Toulouse], Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hormones, facteurs de croissance et physiopathologie vasculaire, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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), and Simon, Marie Francoise
Subjects: Cell type, Pathology, medicine.medical_specialty, Inflammation, Coronary Artery Disease, Biology, MESH: Phenotype, Sensitivity and Specificity, Muscle, Smooth, Vascular, MESH: Gene Expression Profiling, MESH: Reverse Transcriptase Polymerase Chain Reaction, medicine, MESH: DNA Fingerprinting, Humans, Myocyte, MESH: Coronary Artery Disease, Differential display, MESH: Humans, Reverse Transcriptase Polymerase Chain Reaction, Vascular disease, Gene Expression Profiling, General Medicine, MESH: Muscle, Smooth, Vascular, medicine.disease, DNA Fingerprinting, Phenotype, MESH: Sensitivity and Specificity, Gene expression profiling, Cell culture, medicine.symptom
Abstract: International audience; AIM OF THE STUDY: Smooth muscle cells build up the normal media and stabilize atherosclerotic lesions whereas an inflammatory component is determinant for unstable angina. Smooth muscle cells, currently identified by alpha-actin, present a phenotypic heterogeneity and alpha-actin can be reduced in pathology. We tried to characterize vascular cell types, particularly smooth muscle cells, and coronary atherosclerotic tissues, by random genes expression fingerprints. MATERIALS AND METHODS: Expression fingerprints (cDNA electrophoresis) were performed by differential display reverse transcriptase-polymerase chain reaction. Variability of fingerprints was studied for a panel of arterial muscle cell phenotypes and comparisons were made with fingerprints from other cell types (endothelial cells and macrophages). The technique was then applied to human coronary atherectomy samples compared to control human arterial (mammary) smooth muscle. RESULTS: Arterial smooth muscle cells fingerprints were overall similar whatever the cell phenotype (native contractile, dedifferentiated in culture or epithelioid). Moreover, with two primer pairs, the muscular fingerprints markedly differed from the endothelial and the monocytic fingerprints. Application of differential display to coronary atherectomy samples was feasible. Interestingly, the pathological tissues exhibited either smooth muscle-like or smooth muscle-divergent fingerprints. CONCLUSIONS: Smooth muscle cells and inflammatory cells exhibited distinct differential display fingerprint patterns. Thus, a simple expression profile of arbitrary genes provides a molecular bar code tool (pattern signature) useful to characterize vascular cell cultures or tissues. The present work proposes a method to analyze coronary atherectomy samples which estimates their whole quality, muscular versus non muscular (inflammatory), this is of interest for clinical research.
Published: 2007

212. Cytotoxic oxysterols induce caspase-independent myelin figure formation and caspase-dependent polar lipid accumulation

Author: Edmond Kahn, Gérard Lizard, Jean-Marc Riedinger, Thomas Montange, Franck Ménétrier, Anne Vejux, Jeannine Lherminier, Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Microscopie Appliqué à la Biologie et à la Médecine, Institut National de la Santé et de la Recherche Médicale (INSERM), Service Commun de Microscopie Electronique, Institut National de la Recherche Agronomique (INRA), Laboratoire de Biologie Médicale [Centre Georges-François leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Recherche Agronomique ( INRA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Santé - STIC, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Saidi, Vanessa
Subjects: Programmed cell death, Cell Membrane Permeability, Histology, Apoptosis, 03 medical and health sciences, chemistry.chemical_compound, Myelin, 0302 clinical medicine, medicine, polycyclic compounds, Humans, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Propidium iodide, Enzyme Inhibitors, Ketocholesterols, Molecular Biology, Myelin Sheath, Caspase, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Cell Nucleus, 0303 health sciences, biology, Nile red, Lipid metabolism, U937 Cells, Cell Biology, Tunicamycin, Lipid Metabolism, Caspase Inhibitors, Cell biology, Medical Laboratory Technology, medicine.anatomical_structure, chemistry, Caspases, 030220 oncology & carcinogenesis, biology.protein, lipids (amino acids, peptides, and proteins), [SDV.IB]Life Sciences [q-bio]/Bioengineering, Propidium
Abstract: Oxysterols, mainly those oxidized at the C7 position, induce a complex mode of cell death exhibiting some characteristics of apoptosis associated with a rapid induction of lipid rich multilamellar cytoplasmic structures (myelin figures) observed in various pathologies including atherosclerosis. The aim of this study was to determine the relationships between myelin figure formation, cell death, and lipid accumulation in various cell lines (U937, THP-1, MCF-7 [caspase-3 deficient], A7R5) treated either with oxysterols (7-ketocholesterol [7KC], 7beta-hydroxycholesterol, cholesterol-5alpha,6alpha-epoxide, cholesterol-5beta,6beta-epoxide, 25-hydroxycholesterol) or cytotoxic drugs (etoposide, daunorubicin, tunicamycin, rapamycin). Cell death was assessed by the measurement of cellular permeability with propidium iodide, characterization of the morphological aspect of the nuclei with Hoechst 33342, and identification of myelin figures by transmission electron microscopy. Nile Red staining (distinguishing neutral and polar lipids) was used to identify lipid content by flow cytometry and spectral imaging microscopy. Whatever the cells considered, myelin figures were only observed with cytotoxic oxysterols (7KC, 7beta-hydroxycholesterol, cholesterol-5beta, 6beta-epoxide), and their formation was not inhibited by the broad spectrum caspase inhibitor z-VAD-fmk. When U937 cells were treated with oxysterols or cytotoxic drugs, polar lipid accumulation was mainly observed with 7KC and 7beta-hydroxycholesterol. The highest polar lipid accumulation, which was triggered by 7KC, was counteracted by z-VAD-fmk. These findings demonstrate that myelin figure formation is a caspase-independent event closely linked with the cytotoxicity of oxysterols, and they highlight a relationship between caspase activity and polar lipid accumulation.
Published: 2007

213. Profiling of adipokines secreted from human subcutaneous adipose tissue in response to PPAR agonists

Author: Anne Mazzucotelli, Vladimir Stich, Cedric Moro, Eva Klimcakova, Nathalie Viguerie, Jean Galitzky, Karine Lolmède, Dominique Langin, Simon, Marie Francoise, Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]
Subjects: MESH: Hepatocyte Growth Factor, Leptin, Proteomics, Peroxisome Proliferator-Activated Receptors, MESH: Peroxisome Proliferator-Activated Receptors, Adipose tissue, White adipose tissue, Biochemistry, PPAR agonist, 0302 clinical medicine, Adipocytes, MESH: Obesity, MESH: Endothelial Cells, MESH: Cytokines, 0303 health sciences, Hepatocyte Growth Factor, MESH: Proteomics, Stromal vascular fraction, MESH: Gene Expression Regulation, Cytokines, Hepatocyte growth factor, medicine.drug, medicine.medical_specialty, Adipose tissue macrophages, Biophysics, Subcutaneous Fat, Adipokine, 030209 endocrinology & metabolism, Biology, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH: Subcutaneous Fat, Internal medicine, medicine, Humans, Obesity, RNA, Messenger, Molecular Biology, MESH: Adipocytes, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, Interleukin-6, Gene Expression Profiling, Endothelial Cells, MESH: Leptin, Cell Biology, MESH: Interleukin-6, Endocrinology, Gene Expression Regulation
Abstract: International audience; The role of PPARs in the regulation of human adipose tissue secretome has received little attention despite its potential importance in the therapeutic actions of PPAR agonists. Here, we have investigated the effect of selective PPARgamma, PPARalpha, and PPARbeta/delta agonists on the production of adipokines by human subcutaneous adipose tissue. Antibody arrays were used to measure secreted factors in media from cultured adipose tissue explants. Sixteen proteins were produced in significant amounts. Activation of PPARs regulated the production of five proteins. Treatments with the three PPAR agonists decreased the secretion of leptin and interleukin-6. PPARalpha and beta/delta agonists markedly enhanced hepatocyte growth factor secretion whereas PPARbeta/delta down-regulated angiogenin and up-regulated TIMP-1 release. Hepatocyte growth factor, interleukin-6, and TIMP-1 are chiefly expressed in cells from the stromal vascular fraction whereas angiogenin is expressed in both adipocytes and cells from the stromal vascular fraction. Our data show that PPAR agonists modulate secretion of bioactive molecules from the different cell types composing human adipose tissue.
Published: 2007

214. Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity

Author: Dominique Langin, Vladimir Stich, Michaela Vitkova, Nathalie Viguerie, Cedric Moro, Jiri Hanacek, Eva Klimcakova, Magda Bajzova, Jan Polak, Carine Valle, Frédéric Capel, Michaela Kovacikova, Blanka Richterova, Jindra Hejnova, Simon, Marie Francoise, Hepatic and adipose tissue and functions in the metabolic syndrome - HEPADIP - 32591 - OLD, Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Mother and Child Care, Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), The authors' work is supported by Institut National de la Sante' et de la Recherche Me'dicale, Grant GACR 303/04/0158 of the Grant Agency of the Czech Republic, research project of the Ministry of Education of Czech Republic MSM 0021620814, RIOMA project of the Agence Nationale de la Recherche and the project 'Hepatic and adipose tissue and functions in the metabolic syndrome' (HEPADIP, see http://www.hepadip.org/), which is supported by the European Commission as an Integrated Project under the 6th Framework Programe (Contract LSHM-CT-2005-018734), European Project: 32591,HEPADIP, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]
Subjects: Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, RNA, Messenger/metabolism, Adipose tissue, Gene Expression, Retinol-Binding Proteins/*genetics/*metabolism, MESH: Glucose Clamp Technique, Biochemistry, Glucose Transporter Type 4/genetics, 0302 clinical medicine, Endocrinology, Weight loss, MESH: Obesity, Insulin, Gene Expression/physiology, MESH: Diet, Reducing, 2. Zero hunger, 0303 health sciences, MESH: Middle Aged, Glucose Transporter Type 4, Middle Aged, Very low calorie diet, MESH: Insulin Resistance, Adipose Tissue, Female, medicine.symptom, MESH: Retinol-Binding Proteins, Plasma, MESH: Adipose Tissue, Adult, medicine.medical_specialty, MESH: Gene Expression, Diet, Reducing, Diet therapy, food.diet, Calorie restriction, 030209 endocrinology & metabolism, MESH: Insulin, Biology, Obesity/*diet therapy/*physiopathology, Caloric Restriction, MESH: Weight Loss, 03 medical and health sciences, food, Insulin resistance, Internal medicine, Weight Loss, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, RNA, Messenger, MESH: RNA, Messenger, 030304 developmental biology, MESH: Caloric Restriction, Retinol binding protein 4, MESH: Humans, Biochemistry (medical), Adipose Tissue/*physiology, MESH: Adult, MESH: Retinol-Binding Proteins, medicine.disease, Retinol-Binding Proteins, biology.protein, Glucose Clamp Technique, Weight Loss/physiology, MESH: Glucose Transporter Type 4, Insulin Resistance, Insulin/blood, MESH: Female, Retinol-Binding Proteins, Plasma
Abstract: 0021-972X (Print) 0021-972X (Linking) Journal Article Research Support, Non-U.S. Gov't; International audience; CONTEXT: Retinol-binding protein 4 (RBP4) may play a role in the development of insulin resistance. OBJECTIVE: We investigated whether RBP4 adipose tissue mRNA expression and plasma level are related to insulin sensitivity during a diet-induced weight loss. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Obese women followed a dietary intervention composed of a 4-wk very low-calorie diet (VLCD), a 2-month low-calorie diet, and 3-4 months of a weight maintenance (WM) phase. MAIN OUTCOME MEASURES: Clinical investigation was performed before and at the end of each phase. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp. Adipose tissue mRNA and plasma levels of RBP4 were determined using reverse transcription-quantitative PCR and ELISA, respectively. RESULTS: Weight and fat mass decreased during VLCD and were stabilized during WM. Glucose disposal rate increased during VLCD and remained elevated thereafter. Plasma levels of RBP4 decreased after VLCD and, although increasing at subsequent phases, remained lower than prediet values. Adipose tissue mRNA levels were diminished after VLCD, and increased during low-calorie diet and WM to reach basal values. Basal RBP4 levels or diet-induced variations of RBP4 were not different in lean women and two groups of obese women with high- and low-insulin sensitivity. CONCLUSIONS: Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. The study does not bring evidence for a role for RBP4 in the regulation of diet-induced changes in insulin sensitivity.
Published: 2007

215. NF-kappaB is important for TNF-alpha-induced lipolysis in human adipocytes

Author: Laurencikiene, Jurga, Van Harmelen, Vanessa, Arvidsson Nordström, Elisabet, Dicker, Andrea, Blomqvist, Lennart, Näslund, Erik, Langin, Dominique, Arner, Peter, Rydén, Mikael, Simon, Marie Francoise, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Danderyds sjukhus = Danderyd University Hospital, Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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), Department of Surgery, Karolinska Institutet [Stockholm], Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, Perilipin-1, Cell Membrane Permeability, Transcription, Genetic, Lipolysis, Active Transport, Cell Nucleus, Down-Regulation, MESH: NF-kappa B, MESH: Active Transport, Cell Nucleus, MESH: Phosphoproteins, MESH: Down-Regulation, Adipocytes, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH: Lipolysis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, MESH: Cell Membrane Permeability, Phosphorylation, Cells, Cultured, MESH: Adipocytes, MESH: RNA, Messenger, MESH: Humans, MESH: Phosphorylation, Tumor Necrosis Factor-alpha, MESH: Peptides, MESH: Transcription, Genetic, NF-kappa B, Phosphoproteins, MESH: Tumor Necrosis Factor-alpha, Carrier Proteins, Peptides, Signal Transduction, MESH: Cells, Cultured
Abstract: International audience; Tumor necrosis factor-alpha (TNF-alpha) promotes lipolysis in mammal adipocytes via the mitogen-activated protein kinase (MAPK) family, resulting in reduced expression/function of perilipin (PLIN). The role of another pivotal intracellular messenger activated by TNF-alpha, nuclear factor-kappaB (NF-kappaB), has not been recognized. We explored the role of NF-kappaB in TNF-alpha-induced lipolysis of human fat cells. Primary cultures of human adipocytes were incubated in the presence of a cell-permeable peptide that inhibits NF-kappaB signaling (WP). Incubation with WP, but not with a biologically inactive peptide (MP), abolished the nuclear translocation of NF-kappaB and effectively abrogated TNF-alpha-induced lipolysis in a concentration-dependent manner. Western blot analysis demonstrated that although TNF-alpha per se reduced mainly PLIN protein expression, TNF-alpha in the presence of WP resulted in a pronounced combined reduction of both hormone-sensitive lipase (HSL) and PLIN protein. The expression of a set of other lipolytic or adipocyte-specific proteins was not affected. The regulation was presumably at the transcriptional level, because mRNA expression for HSL and PLIN was markedly reduced with TNF-alpha in the presence of NF-kappaB inhibition. This was confirmed in gene reporter assays using human PLIN and HSL promoter constructs. We conclude that in the presence of NF-kappaB inhibition, TNF-alpha-mediated lipolysis is reduced, which suggests that NF-kappaB is essential for retained human fat cell lipolysis.
Published: 2007

216. Serious Games for Vocational Training: From Emotional Labor to Knowledge Transfer

Author: Julian Alvarez, Antoine Taly, Lydia Martin, Centre de recherche sur le travail et le développement (CRTD), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut national supérieur du professorat et de l'éducation - Académie de Lille - Hauts-de-France (INSPE LHdF), Université Lille Nord de France (COMUE), Laboratoire en Design Visuel et Urbain - EA 2445 (DeVisu), INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS), HESAM Université (HESAM)-HESAM Université (HESAM), Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)
Subjects: [SHS.INFO]Humanities and Social Sciences/Library and information sciences, 4. Education, 05 social sciences, Applied psychology, [SHS.PSY]Humanities and Social Sciences/Psychology, 050301 education, Emotional labor, Vocational education, 0502 economics and business, Psychology, 0503 education, Knowledge transfer, ComputingMilieux_MISCELLANEOUS, 050203 business & management
Abstract: International audience
Published: 2021

217. Lattice model for amyloid peptides: OPEP force field parametrization and applications to the nucleus size of Alzheimer’s peptides

Author: Derreumaux, Philippe [Laboratoire de Biochimie Théorique, UPR 9080, CNRS, Université Denis Diderot, Sorbonne Paris Cité IBPC, 13 rue Pierre et Marie Curie, 75005 Paris (France)]
Published: 2016
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218. Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue

Author: Cedric Moro, Anne Bouloumié, Michel Berlan, Karine Lolmède, Dominique Langin, V. Stich, Max Lafontan, Jean Galitzky, Peter Arner, Eva Klimcakova, Simon, Marie Francoise, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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), Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de pharmacologie médicale et clinique, CHU Toulouse [Toulouse], Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: MESH: Inflammation, MESH: Atrial Natriuretic Factor, Endocrinology, Diabetes and Metabolism, Adipose tissue, White adipose tissue, 030204 cardiovascular system & hematology, Polymerase Chain Reaction, 0302 clinical medicine, Atrial natriuretic peptide, Abdomen, Adipocytes, Cells, Cultured, 0303 health sciences, MESH: Cytokines, MESH: Middle Aged, MESH: Adiponectin, Middle Aged, MESH: Insulin Resistance, Adipose Tissue, Cytokines, Female, Adiponectin, medicine.symptom, hormones, hormone substitutes, and hormone antagonists, MESH: Adipose Tissue, Atrial Natriuretic Factor, MESH: Cells, Cultured, Adult, medicine.medical_specialty, Adipose tissue macrophages, Adipokine, Inflammation, MESH: Abdomen, 03 medical and health sciences, Insulin resistance, MESH: RNA, Internal medicine, Internal Medicine, medicine, Lipolysis, Humans, MESH: Overweight, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, business.industry, Macrophages, MESH: Macrophages, MESH: Polymerase Chain Reaction, MESH: Adult, Overweight, medicine.disease, Endocrinology, RNA, Insulin Resistance, business, MESH: Female
Abstract: International audience; AIMS/HYPOTHESIS: Increased adipose tissue secretion of adipokines and cytokines has been implicated in the chronic low-grade inflammation state and insulin resistance associated with obesity. We tested here whether the cardiovascular and metabolic hormone atrial natriuretic peptide (ANP) was able to modulate adipose tissue secretion of several adipokines (derived from adipocytes) and cytokines (derived from adipose tissue macrophages). SUBJECTS AND METHODS: We used protein array to measure the secretion of adipokines and cytokines after a 24-h culture of human subcutaneous adipose tissue pieces treated or not with a physiological concentration of ANP. The effect of ANP on protein secretion was also directly studied on isolated adipocytes and macrophages. Gene expression was measured by real-time RT-quantitative PCR. RESULTS: ANP decreased the secretion of the pro-inflammatory cytokines IL-6 and TNF-alpha, of several chemokines, and of the adipokines leptin and retinol-binding protein-4 (RBP-4). The secretion of the anti-inflammatory molecules IL-10 and adiponectin remained unaffected. The cytokines were mainly expressed in macrophages that expressed all components of the ANP-dependent signalling pathway. The adipokines, leptin, adiponectin and RBP-4 were specifically expressed in mature adipocytes. ANP directly inhibited the secretion of IL-6 and monocyte chemoattractant protein-1 by macrophages. The inhibitory effects of ANP on leptin and growth-related oncogene-alpha secretions were not seen under selective hormone-sensitive lipase inhibition. CONCLUSIONS/INTERPRETATION: We suggest that ANP, either by direct action on adipocytes and macrophages or through activation of adipocyte hormone-sensitive lipase, inhibits the secretion of factors involved in inflammation and insulin resistance.
Published: 2006

219. Flow cytometry and spectral imaging multiphoton microscopy analysis of CD36 expression with quantum dots 605 of untreated and 7-ketocholesterol-treated human monocytic cells

Author: Kahn, E., Menetrier, F., Vejux, A., Montange, T., Dumas, D., Riedinger, J. M., Frédérique Frouin, Tourneur, Y., Brau, F., Stoltz, J. F., Lizard, G., Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire ( PTIBC-IBISA Nancy ), Université Henri Poincaré - Nancy 1 ( UHP ), Laboratoire de Biologie Médicale [Centre Georges-François leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Commun de Quantimétrie, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire (PTIBC-IBISA Nancy), Université Henri Poincaré - Nancy 1 (UHP), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université Claude Bernard Lyon 1 (UCBL), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Nice Sophia Antipolis (... - 2019) (UNS), and Dumas, Dominique
Subjects: CD36 Antigens, MESH: Photons, MESH : Flow Cytometry, MESH: Algorithms, MESH: Flow Cytometry, MESH: U937 Cells, MESH : Quantum Dots, MESH: Monocytes, Monocytes, MESH : Microscopy, Fluorescence, Multiphoton, MESH : Photons, Quantum Dots, MESH : Cells, Cultured, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Ketocholesterols, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cells, Cultured, MESH : Algorithms, MESH : Ketocholesterols, Photons, MESH: Humans, MESH: Antigens, CD36, MESH : Humans, MESH: Ketocholesterols, U937 Cells, MESH: Quantum Dots, Flow Cytometry, MESH : Antigens, CD36, Microscopy, Fluorescence, Multiphoton, MESH : Monocytes, MESH : U937 Cells, MESH: Microscopy, Fluorescence, Multiphoton, Algorithms, MESH: Cells, Cultured
Abstract: To evaluate CD36 expression with quantum dots 605 (QDs 605) on untreated and 7-ketocholesterol (7KC)-treated monocytic U937 cells by flow cytometry (FCM) and confocal and multiphoton laser scanning microscopy (CLSM).Cells were analyzed by CLSM, following flow cytometric quantification of CD36 expression and 7KC uptake. Image sequences were obtained by spectral analysis in monophoton and multiphoton CLSM and analyzed by the factor analysis of medical image sequences (FAMIS) algorithm to differentiate emission spectra. In CLSM analysis, cell deposits were screened in ultraviolet excitation modes to optimize the possibilities of QDs 605 and have the benefit of nuclei counterstaining by DAPI.FCM and CLSM reveal the expression of CD36 by means of QDs 605. FCM provides information on 7KC uptake. CLSM provides the localization of 7KC vs. DAPI. As factor curves and images show the red, narrow emission of QDs 605 vs. violet and blue emissions of 7KC and DAPI, respectively, a reliable identification of CD36 is obtained.QDs 605 are useful tools to perform antigenic expression in FCM and CLSM. Moreover, CLSM and subsequent spectral analysis provide a more specific characterization of QDs 605 fluorescent emission in the UV excitation mode and a simultaneous identification of 7KC.
Published: 2006

220. A ROD–CONE DYSTROPHY IS SYSTEMATICALLY ASSOCIATED TO THE RTN4IP1 RECESSIVE OPTIC ATROPHY

Author: Patrizia Amati-Bonneau, Xavier Zanlonghi, Claire-Marie Dhaenens, Gaël Manes, Béatrice Bocquet, Agathe Roubertie, Isabelle Meunier, Guy Lenaers, Majida Charif, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Mohamed 1 Oujda MAROC, UF Génopathies - Laboratoire de Biochimie et Biologie Moléculaire [Lille] (LBBM), Université de Lille, Sciences et Technologies-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Clinique Jules-Vernes [Nantes], 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and LENAERS, Guy
Subjects: Male, Visual acuity, genetic structures, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Visual Acuity, inherited optic neuropathy, RTN4IP1, Original Study, Fluorescein Angiography, Child, rod–cone dystrophy, medicine.diagnostic_test, General Medicine, Middle Aged, Pedigree, [SDV] Life Sciences [q-bio], Phenotype, Mitochondrial respiratory chain, Female, medicine.symptom, Tomography, Optical Coherence, Adult, medicine.medical_specialty, Adolescent, Fundus Oculi, Retinal ganglion, Mitochondrial Proteins, Young Adult, Atrophy, Ophthalmology, Electroretinography, medicine, Rod-cone dystrophy, Humans, Retrospective Studies, Cerebellar ataxia, business.industry, recessive disease, Dystrophy, DNA, medicine.disease, eye diseases, Mutation, sense organs, Visual Fields, Carrier Proteins, business, Cone-Rod Dystrophies
Abstract: Although RTN4IP1 has been firmly associated to recessive optic atrophies, we identified by systematic examination of the 55° fundus autofluorescence frames and the peripheral spectral-domain optical coherence tomographic images, a progressive rod–cone dystrophy in all individuals with biallelic RTN4IP1 mutations., Purpose: RTN4IP1 biallelic mutations cause a recessive optic atrophy, sometimes associated to more severe neurological syndromes, but so far, no retinal phenotype has been reported in RTN4IP1 patients, justifying their reappraisal. Methods: Seven patients from four families carrying biallelic RTN4IP1 variants were retrospectively reviewed, with emphasis on their age of onset, visual acuity, multimodal imaging including color and autofluorescence frames, spectral-domain optical coherence tomography with RNFL and macular analyses. Results: Seven patients from four RTN4IP1 families developed in their first decade of life a bilateral recessive optic atrophy with severe central visual loss, and primary nystagmus developed in 5 of 7 patients. Six patients were legally blind. In a second stage, the seven individuals developed a rod–cone dystrophy, sparing the macular zone and the far periphery. This retinal damage was identified by 55° field fundus autofluorescence frames and also by spectral-domain optical coherence tomography scans of the temporal part of the macular zone in five of the seven patients. Full-field electroretinography measurements disclosed reduced b-wave amplitude of the rod responses in all patients but two. Family 4 with the p.R103H and c.601A > T (p.K201*) truncating mutation had further combined neurological signs with cerebellar ataxia, seizures, and intellectual disability. Conclusion: RTN4IP1 recessive optic atrophy is systematically associated to a rod–cone dystrophy, which suggests that both the retinal ganglion cells and the rods are affected as a result of a deficit in the mitochondrial respiratory chain. Thus, systematic widefield autofluorescence frames and temporal macular scans are recommended for the evaluation of patients with optic neuropathies.
Published: 2020

221. Premature termination codons in SOD1 causing Amyotrophic Lateral Sclerosis are predicted to escape the nonsense-mediated mRNA decay

Author: Anne Polge, Claire Guissart, Jovana Kantar, Kevin Mouzat, Paul Vilquin, Cédric Raoul, Baptiste Louveau, Serge Lumbroso, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biochimie [CHRU Nîmes], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Raoul, Cédric, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: endocrine system diseases, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Nonsense-mediated decay, SOD1, Mutation, Missense, lcsh:Medicine, Biology, RNA decay, Article, 03 medical and health sciences, 0302 clinical medicine, Superoxide Dismutase-1, medicine, Genetics, Missense mutation, Humans, RNA, Messenger, Motor neuron disease, Amyotrophic lateral sclerosis, lcsh:Science, Gene, 030304 developmental biology, 0303 health sciences, Messenger RNA, Multidisciplinary, Molecular medicine, Amyotrophic Lateral Sclerosis, Medical genetics, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, humanities, 3. Good health, Nonsense Mediated mRNA Decay, Codon, Nonsense, Codon, Terminator, lcsh:Q, Haploinsufficiency, 030217 neurology & neurosurgery
Abstract: Amyotrophic lateral sclerosis (ALS) is the most common and severe adult-onset motoneuron disease and has currently no effective therapy. Approximately 20% of familial ALS cases are caused by dominantly-inherited mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), which represents one of the most frequent genetic cause of ALS. Despite the overwhelming majority of ALS-causing missense mutations in SOD1, a minority of premature termination codons (PTCs) have been identified. mRNA harboring PTCs are known to be rapidly degraded by nonsense-mediated mRNA decay (NMD), which limits the production of truncated proteins. The rules of NMD surveillance varying with PTC location in mRNA, we analyzed the localization of PTCs in SOD1 mRNA to evaluate whether or not those PTCs can be triggered to degradation by the NMD pathway. Our study shows that all pathogenic PTCs described in SOD1 so far can theoretically escape the NMD, resulting in the production of truncated protein. This finding supports the hypothesis that haploinsufficiency is not an underlying mechanism of SOD1 mutant-associated ALS and suggests that PTCs found in the regions that trigger NMD are not pathogenic. Such a consideration is particularly important since the availability of SOD1 antisense strategies, in view of variant treatment assignment.
Published: 2020

222. Early Detection of Relapse by ctDNA Sequencing in a Patient with Metastatic Thymic Tumor and MEN1 Mosaicism

Author: Arnaud Lagarde, Lauriane Le Collen, Camille Boulagnon, Hedia Brixi, Anne Durlach, Grégory Mougel, Thomas Cuny, Brigitte Delemer, Anne Barlier, Pauline Romanet, 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), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie et de Biologie Moléculaire [Hôpital de la Conception - APHM], and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: Thymoma, Mosaicism, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Biochemistry (medical), Clinical Biochemistry, Neoplasms, Second Primary, Thymus Neoplasms, Biochemistry, Circulating Tumor DNA, Endocrinology, Biomarkers, Tumor, Multiple Endocrine Neoplasia Type 1, Humans, Neoplasm Recurrence, Local
Abstract: Context Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by inactivating mutations in the MEN1 gene. In the literature, few cases of MEN1 have been reported because of mosaic MEN1 mutations. Objective We performed an extensive molecular characterization in several lesions and blood samples, including plasmatic circulating cell-free DNA (ccfDNA) in an exceptional case of a patient with MEN1 mosaicism causing primary hyperparathyroidism, multiple pancreatic neuroendocrine tumors (NETs), and a metastatic thymic NET. Methods Blood, ccfDNA and multiple tissue analysis were performed by next-generation sequencing. Results MEN1 mosaicism was confirmed by multiple tissue analysis. Somatic analysis of the largest pancreatic NET revealed the same MEN1 second-hit mutation as found in the thymic lesion, demonstrating its metastatic origin from the thymic lesion. Moreover, in ccfDNA we found the mosaic MEN1 mutation but also the somatic second-hit mutation found in the thymic primary tumor, revealing the presence of circulating tumor DNA (ctDNA). After surgical removal of the pancreatic metastasis, the mutated fraction of both mutations decreased, before increasing again several weeks before a new clinical relapse, suggesting that thymic ctDNA may be used as an early tumor biomarker. Conclusion This exceptional MEN1 case highlighted (1) the importance of looking for MEN1 mosaicism, (2) that MEN1 mosaicism can cause very aggressive disease, and (3) the interest in analyzing ccfDNA for confirming MEN1 mosaicism but also as a potential tumor biomarker for NET.
Published: 2022

223. Explicit models of motions to understand protein side-chain dynamics

Author: Nicolas Bolik-Coulon, Olivier Languin-Cattoën, Diego Carnevale, Milan Zachrdla, Damien Laage, Fabio Sterpone, Guillaume Stirnemann, Fabien Ferrage, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - 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), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Ferrage, Fabien
Subjects: Diffusion, Chemical Physics (physics.chem-ph), [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Motion, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Entropy, Physics - Chemical Physics, General Physics and Astronomy, FOS: Physical sciences, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Molecular Dynamics Simulation
Abstract: International audience; Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of relaxation in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions of motions. Model-free types of correlation functions cannot describe a large carbon-13 relaxation dataset in protein sidechains. Here, we use molecular dynamics simulations to design explicit models of motion and solve Fokker-Planck diffusion equations. These models of motion provide better agreement with relaxation data, mechanistic insight and a direct link to configuration entropy.
Published: 2022

224. Relevance of cortisol and copeptin blood concentration changes in an experimental pain model

Author: Blum, Claudine, Velly, Laëtitia, Brochet, Christine, Ziegler, Frédéric, Tavolacci, Marie-Pierre, Hausfater, Pierre, Lvovschi, Virginie Eve, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medical University Clinic, Kantonsspital Aarau, Tellstrasse 25, Haus 7, 5001, Aarau, Switzerland., BIOSFAST [CHU Pitié-Salpêtrière] (GRC 14), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-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), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des urgences [CHU Rouen], and douville, sabine
Subjects: [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Abstract: International audience; Abstract The effect of pain and analgesics on stress biomarkers is not well studied. We evaluated the effect of acute pain and analgesics on serum cortisol and copeptin in an experimental pain model in healthy volunteers. Healthy volunteers presented at 8 a.m. for an experimental pain stimulation. Cortisol and copeptin levels were measured before, during and after electrophysiological stimulation, first before and then during opioid delivery. Difference in biomarker levels compared to baseline levels was calculated, and potential influencing factors were evaluated by linear regression analysis. Cortisol decreased by 13% during the 10 min of rest at baseline, but copeptin did not change significantly. Cortisol had a median decrease of −24% or −83 nmol/l (−44 to −124 nmol/l, p = 0.0002) during the electrophysiological stimulation training session, while the median difference for copeptin was −22% or −1.01 pmol/l (−2.35 to 0.08 pmol/l, p = 0.0003). After administration of opioids, cortisol did not decrease but increased by 3% (p = 0.043), indicating an increasing opioids effect on cortisol. This effect was not visible for copeptin (median change −0.003 pmol/l (−0.50 to 0.24), p = 0.45). In this experimental pain model performed in the morning, moderate pain did not have a relevant effect on cortisol or copeptin levels, whereas opioids led to a discrete peak of cortisol. Clinicaltrials.gov identifier: NCT01975753 (registered on November 5, 2013, before start of recruitment).
Published: 2022

225. Multiple endocrine neoplasia type 1 caused by mosaic mutation: clinical follow-up and genetic counseling?

Author: Lucie Coppin, Sophie Giraud, Eric Pasmant, Arnaud Lagarde, Marie-Odile North, Lauriane Le-Collen, Valérie Aubert, Grégory Mougel, Miriam Ladsous, Alyzée Louboutin, Hedia Brixi, Magalie Haissaguerre, Nicolas Scheyer, Marc Klein, Antoine Tabarin, Brigitte Delemer, Anne Barlier, Marie-Françoise Odou, Pauline Romanet, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Laboratoire de Biochimie et de Biologie Moléculaire [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Universitaire de Reims (CHU Reims), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Sans affiliation, Hôpital Claude Huriez [Lille], Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), All phases of this study were supported by grants from the Institut National de lutte contre le Cancer (INCa), the MarMaRa Institute, and the French Ministry of Health. The project resulting in this publication received funding from the Excellence Initiative of Aix Marseille University -A*Midex- a French 'Investissement d'Avenir' - Institute MarMaRa AMX-19-IET- 007., and Gall, Valérie
Subjects: next generation sequencing, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.GEN]Life Sciences [q-bio]/Genetics, Heterozygote, Endocrinology, Diabetes and Metabolism, Genetic Counseling, General Medicine, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, genetic testing, hyperparathyroidism, Endocrinology, MEN1, mosaicism, NGS, Mutation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Multiple Endocrine Neoplasia Type 1, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, mosaic, thymic NET, Follow-Up Studies
Abstract: MEN1 is an autosomal dominant hereditary syndrome characterized by several endocrine tumors, in most cases affecting the parathyroid glands, pancreas, and anterior pituitary. It is the result of inactivating mutations in the tumor suppressor gene MEN1. More than 1300 different mutations have been identified in this gene. Mosaic MEN1 mutations have been previously described in only a few patients in the literature. In this paper, we provide a review of six cases of MEN1 mosaicism reported in the literature supplemented with six additional cases described by the French TENgen network of laboratories. This review highlights that (i) MEN1 mosaicism is not associated with a mild phenotype and results in the same natural history as heterozygous MEN1 mutation and (ii) that more systematic detection of MEN1 mosaic mutation enables improvements in both patient monitoring and genetic counseling.
Published: 2022

226. [Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient]

Author: Chabaâ, Laïla, Monnier, Nicole, Dahri, Saloua, Jorio, M., Lunardi, Joël, Chabraoui, Layachi, Roux-Buisson, Nathalie, Laboratoire de biochimie, Hôpital d'enfants de Rabat, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de pédiatrie, Ce travail a été réalisé en partie grâce au financement (NM) par le GIS-Maladies Rares et l'Association du Syndrome de Lowe., and Collaboration
Subjects: Male, MESH: Sequence Homology, Amino Acid, Molecular Sequence Data, MESH: Sequence Alignment, Mutation, Missense, MESH: Amino Acid Sequence, MESH: Base Sequence, Animals, Humans, MESH: Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amino Acid Sequence, OCRL1, Sequence Deletion, MESH: Mutation, Missense, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Sequence Homology, Amino Acid, syndrome de Lowe, Infant, MESH: Sequence Deletion, MESH: Amino Acid Substitution, MESH: Infant, MESH: Male, Phosphoric Monoester Hydrolases, Morocco, Oculocerebrorenal Syndrome, Amino Acid Substitution, MESH: Morocco, 5 biphosphate 5-phosphatase, MESH: Phosphoric Monoester Hydrolases, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], inositol 4, mutation, Sequence Alignment, MESH: Oculocerebrorenal Syndrome
Abstract: International audience; The oculo-cerebro-renal syndrome of Lowe is a rare X-linked disorder, caused by the inositol biphosphate 5-phosphatase deficiency, localized to the Golgi complex. Several mutations were reported in patient's OCRL gene leading to enzyme deficiency. We report a Moroccan case of OCRL syndrome of Lowe with a neo mutation in exon 10. The patient aged of 19 months was referred to our medical centre because of a psychomotor retardation. He had a medical history of eye abnormalities including cataract and bilateral glaucoma, diagnosed when he was 5 weeks old. Cataract has been treated after chirurgical therapy but ocular hypertonia persisted. Physical examination revealed an axial hypotonia and walking difficulties. Laboratory tests revealed a moderate acidosis (20 mmol/L), a slight decrease of serum phosphate level (24 mg/L) and an increased serum phosphatase activity. Further studies showed mild proteinuria, urinary bicarbonates loosing and generalised hyperaminoaciduria. Based on both clinical and biological data, Lowe syndrome has been suggested. In this context, molecular investigation has been performed using dHPLC/sequencing techniques which allow identifying an original mutation c.776T>C (p.Phe259Ser), localized on the exon 10 of the OCRL gene. The mutation was not found in the probant's mother suggesting a neo mutation. Lowe syndrome is a rare hereditary X-linked disorder resulting from a variety of heterogeneous mutations of OCRL gene. Indeed, numerous mutations have been reported, variations were noted concerning their localization as well as their type. To our knowledge, this is the first report of the neo mutation c.776T>C of OCRL gene and the first published case report of the Lowe syndrome in a Moroccan patient.
Published: 2005

227. 7-Ketocholesterol favors lipid accumulation and colocalizes with Nile Red positive cytoplasmic structures formed during 7-ketocholesterol-induced apoptosis: analysis by flow cytometry, FRET biphoton spectral imaging microscopy, and subcellular fractionation

Author: Ginette Bessède, Gérard Lizard, Edmond Kahn, Anne Vejux, Jean-Marc Riedinger, Andrew Todd-Pokropek, Anne Athias, Franck Ménétrier, Frédérique Frouin, Eric Ogier-Denis, Jean-François Stoltz, Dominique Dumas, Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire ( PTIBC-IBISA Nancy ), Université Henri Poincaré - Nancy 1 ( UHP ), Plateforme Lipidomique [Dijon] ( LAP ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de Biologie Médicale [Centre Georges-François leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Faculté de Médecine Xavier Bichat, Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire (PTIBC-IBISA Nancy), Université Henri Poincaré - Nancy 1 (UHP), Plateforme Lipidomique [Dijon] (LAP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: MESH: Flow Cytometry, Apoptosis, 7. Clean energy, law.invention, MESH : Phosphatidylcholines, 0302 clinical medicine, Fluorescence Resonance Energy Transfer, MESH : Fluorescent Dyes, Enzyme Inhibitors, MESH: Lipid Metabolism, 0303 health sciences, MESH : Cell Nucleus, Flow Cytometry, MESH: Image Processing, Computer-Assisted, Cholesterol, MESH : Propidium, 030220 oncology & carcinogenesis, MESH : U937 Cells, MESH: Microscopy, Electron, Transmission, MESH: Cell Fractionation, MESH : Image Processing, Computer-Assisted, MESH: Propidium, Propidium, MESH: Cell Nucleus, MESH : Sphingomyelins, MESH: Mitochondria, Cell Fractionation, Filipin, Permeability, Pathology and Forensic Medicine, 03 medical and health sciences, Microscopy, Electron, Transmission, Oxazines, MESH: Membrane Potentials, Humans, Propidium iodide, MESH: Humans, MESH : Oxazines, MESH : Humans, Nile red, MESH: Phosphatidylcholines, Lipid Metabolism, Förster resonance energy transfer, chemistry, MESH: Subcellular Fractions, Cytoplasmic Structures, Benzimidazoles, MESH : Apoptosis, MESH: Fluorescence Resonance Energy Transfer, MESH: Sphingomyelins, Membrane Potentials, chemistry.chemical_compound, MESH: Cholesterol, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], law, MESH : Lipid Metabolism, Image Processing, Computer-Assisted, Fluorescence microscope, MESH : Membrane Potentials, Ketocholesterols, MESH : Cholesterol, MESH: Ketocholesterols, U937 Cells, MESH: Fluorescent Dyes, Mitochondria, Sphingomyelins, MESH: Intracellular Membranes, MESH : Microscopy, Electron, Transmission, Biochemistry, MESH : Benzimidazoles, MESH: Enzyme Inhibitors, MESH: Permeability, MESH : Cell Fractionation, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), MESH : Mitochondria, Cell fractionation, Subcellular Fractions, Histology, MESH : Flow Cytometry, MESH: U937 Cells, MESH : Subcellular Fractions, Confocal microscopy, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Fluorescent Dyes, 030304 developmental biology, MESH : Ketocholesterols, Cell Nucleus, MESH : Enzyme Inhibitors, MESH: Apoptosis, Lipid metabolism, Intracellular Membranes, Cell Biology, MESH : Cytoplasmic Structures, MESH: Cytoplasmic Structures, MESH : Intracellular Membranes, MESH : Permeability, MESH : Fluorescence Resonance Energy Transfer, MESH: Benzimidazoles, MESH: Oxazines
Abstract: Background Oxidized low-density lipoproteins play key roles in atherosclerosis. Their toxicity is at least in part due to 7-ketocholesterol (7KC), which is a potent inducer of apoptosis. In this study on human promonocytic U937 cells, we determined the effects and the interactions of 7KC with cellular lipids during 7KC-induced apoptosis. Methods Morphologic and functional changes were investigated by microscopic and flow cytometric methods after staining with propidium iodide, 3,3′-dihexyloxacarbocyanine iodide, and Hoechst 33342. Cellular lipid content was identified by using filipin to quantify free cholesterol and Nile Red (NR), which emit a yellow or orange-red fluorescence in the presence of neutral and polar lipids, respectively. After staining with NR, interactions of 7KC with cellular lipids were identified by fluorescence resonance energy transfer biphoton spectral imaging confocal microscopy and by subcellular fractionation, gas chromatography, and mass spectrometry. Results During 7KC-induced apoptosis the fluorescence from filipin and the ratio of measured (orange-red vs. yellow) fluorescence of NR were enhanced. Spectral analysis of images obtained in biphoton mode and resulting factor images demonstrated the occurrence of fluorescence resonance energy transfer between 7KC and NR and the subsequent colocalization of 7KC and NR. These data were in agreement with biochemical characterization and demonstrated that 7KC and neutral and polar lipids accumulate in NR-stained cytoplasmic structures. Conclusions During 7KC-induced apoptosis, 7KC modifies the cellular content of neutral and polar lipids, favors free cholesterol accumulation, and colocalizes with neutral and polar lipids that are inside NR-stained cytoplasmic structures. © 2005 Wiley-Liss, Inc.
Published: 2005

228. FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol

Author: Kahn, E., Vejux, A., Dumas, D., Montange, T., Frédérique Frouin, Robert, V., Riedinger, J. M., Stoltz, J. F., Gambert, P., Todd-Pokropek, A., Lizard, G., Laboratoire d'Imagerie Fonctionnelle ( LIF ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire ( PTIBC-IBISA Nancy ), Université Henri Poincaré - Nancy 1 ( UHP ), Analysis, perception and recognition of speech ( PAROLE ), INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Laboratoire Lorrain de Recherche en Informatique et ses Applications ( LORIA ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université Henri Poincaré - Nancy 1 ( UHP ) -Université Nancy 2-Institut National Polytechnique de Lorraine ( INPL ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Henri Poincaré - Nancy 1 ( UHP ) -Université Nancy 2-Institut National Polytechnique de Lorraine ( INPL ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie Médicale [Centre Georges-François leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Plateforme Lipidomique [Dijon] ( LAP ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Plate-forme Imagerie et Biophysique Cellulaire et Tissulaire (PTIBC-IBISA Nancy), Université Henri Poincaré - Nancy 1 (UHP), Analysis, perception and recognition of speech (PAROLE), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Plateforme Lipidomique [Dijon] (LAP), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Dumas, Dominique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: MESH: Cell Death, MESH: Fluorescence Resonance Energy Transfer, MESH: Mitochondria, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH : Flow Cytometry, MESH: Flow Cytometry, MESH: U937 Cells, MESH: Monocytes, Monocytes, Membrane Potentials, MESH : Staining and Labeling, MESH : Microscopy, Fluorescence, Multiphoton, Oxazines, Fluorescence Resonance Energy Transfer, Image Processing, Computer-Assisted, Humans, MESH: Membrane Potentials, MESH: Microscopy, Confocal, MESH : Membrane Potentials, MESH : Fluorescent Dyes, MESH : Microscopy, Confocal, Ketocholesterols, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Fluorescent Dyes, MESH : Ketocholesterols, Microscopy, Confocal, MESH: Humans, MESH : Oxazines, Cell Death, Staining and Labeling, MESH : Humans, MESH: Ketocholesterols, U937 Cells, Flow Cytometry, MESH: Fluorescent Dyes, MESH: Image Processing, Computer-Assisted, Mitochondria, MESH: Staining and Labeling, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Microscopy, Fluorescence, Multiphoton, MESH : Monocytes, MESH : Fluorescence Resonance Energy Transfer, MESH : Cell Death, MESH : U937 Cells, MESH: Microscopy, Fluorescence, Multiphoton, MESH : Mitochondria, MESH: Oxazines, MESH : Image Processing, Computer-Assisted
Abstract: To show the effect of 7-ketocholesterol (7KC) on cellular lipid content by means of flow cytometry and the interaction of 7KC with Nile Red (NR) via ultraviolet fluorescence resonance energy transfer (FRET) excitation of NR on U937 monocytic cells by means of 2-photon excitation confocal laser scanning microscopy (CLSM).Untreated and 7KC-treated U937 cells were stained with NR and analyzed by flow cytometry and CLSM. 3D sequences of images were obtained by spectral analysis in a 2-photon excitation CLSM and analyzed by the factor analysis of medical image sequences (FAMIS) algorithm, which provides factor curves and images. Factor images are the result of the FAMIS image processing method, which handles emission spectra. In FRET analysis, preparations are screened at selected UV wavelengths to avoid emission of NR in the absence of 7KC.During 7KC-induced cell death,flow cytometry and CLSM revealed a modification of the cellular lipid content. Factor images show FRET occurrence and subsequent colocalization of 7KC and NR.This investigation established the utility of 2-photon excitation CLSM to assess colocalization of 7KC with NR by FRET and to identify and distinguish polar and neutral lipids stained by NR that accumulate from the effect of 7KC.
Published: 2004

229. Serum GFAP in multiple sclerosis: correlation with disease type and MRI markers of disease severity

Author: Claire Duflos, Jeremy Deverdun, Frédéric Pinna, Tobias Kober, Clarisse Carra-Dalliere, Bénédicte Maréchal, Ricardo Corredor Jerez, Christophe Hirtz, Pauline Prin, Xavier Ayrignac, Nicolas Menjot de Champfleur, Sylvain Lehmann, Mahmoud Charif, Mário João Fartaria, Pierre Labauge, Aleksandra Maleska Maceski, Emmanuelle Le Bars, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Département de Neuroradiologie[Montpellier], Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] (I2FH), Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Ecole Polytechnique Fédérale de Lausanne (EPFL), Bodescot, Myriam, CRC Sclérose en Plaques [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Economic Evaluation Unit [Montpellier], Laboratoire de Biochimie – Protéomique Clinique [Montpellier] (LBPC), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Siemens Healthcare [Lausanne, Suisse], and Université de Lausanne (UNIL)
Subjects: Male, 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuroimmunology, lcsh:Medicine, Disease, Severity of Illness Index, Gastroenterology, 0302 clinical medicine, Cerebrospinal fluid, Neurofilament Proteins, Medicine, lcsh:Science, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Multidisciplinary, medicine.diagnostic_test, Brain, Middle Aged, Multiple Sclerosis, Chronic Progressive, Magnetic Resonance Imaging, White Matter, biomarker, Biomarker (medicine), Female, damage, Adult, medicine.medical_specialty, Neurofilament, Context (language use), neurofilament, Article, Multiple sclerosis, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Glial Fibrillary Acidic Protein, Severity of illness, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], business.industry, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Magnetic resonance imaging, medicine.disease, cerebrospinal-fluid, Cross-Sectional Studies, 030104 developmental biology, neuronal markers, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, business, 030217 neurology & neurosurgery
Abstract: Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.
Published: 2020

230. Homocysteine concentration and adenosine A2A receptor production by peripheral blood mononuclear cells in coronary artery disease patients

Author: Giovanna Mottola, Laurie Bruzzese, Patrick Mace, Donato Vairo, Christine Criado, Pierre Deharo, Clair Guiol, Marine Gaudry, Emmanuel Fenouillet, Mélanie Gaubert, Mohamed Chefrour, Marguerite Gastaldi, Régis Guieu, Nathalie Kipson, Marion Marlinge, Julien Fromonot, Thomas Cuisset, Franck Paganelli, Jean Ruf, Assistance Publique - Hôpitaux de Marseille (APHM), 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), Département de Biochimie [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Biochimie [CHU de la Timone], and Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Hyperhomocysteinemia, Homocysteine, Receptor, Adenosine A2A, Arbitrary unit, [SDV]Life Sciences [q-bio], Adenosine A2A receptor, Coronary Artery Disease, Peripheral blood mononuclear cell, A2A receptor, Pathogenesis, 03 medical and health sciences, Coronary circulation, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Cells, Cultured, Aged, business.industry, Cell Biology, Original Articles, homocysteine, medicine.disease, Adenosine, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, adenosine, 030220 oncology & carcinogenesis, Leukocytes, Mononuclear, Molecular Medicine, Original Article, Female, business, medicine.drug
Abstract: International audience; Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A2A receptors (A2AR). We addressed in CAD patients the relationship between HCy and A2AR production, and in cellulo the effect of HCy on A2AR function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A2AR production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A2A R production as well as on basal and stimulated cAMP production following A2A R activation by an agonist‐like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7‐45] vs 8 [5‐12] µM, P < 0.001). A2A R production was lower in patients vs controls (1.1[0.62‐1.6] vs 1.53[0.7‐1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A2A R production (r = −0.43; P < 0.0001), with decreased A2A R production above 25 µM HCy. In cellulo, HCy inhibited A2AR production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A2A R production in CAD patients, as well as with A2A R and cAMP production in cellulo. The decrease in A2A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.
Published: 2020

231. Visualisation des structures protéiques - outils et tendances

Author: Marc Baaden, Xavier Martinez, Matthieu Chavent, Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ANR-11-LABX-0011,DYNAMO,Dynamique des membranes transductrices d'énergie : biogénèse et organisation supramoléculaire.(2011), ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011), and ANR-16-CE05-0024,Enzymor,Bases moléculaires de l'immobilisation fonctionnelle d'enzymes pour des biopiles performantes(2016)
Subjects: Protein visualization, Protein Conformation, Scientific literature, 010402 general chemistry, 01 natural sciences, Biochemistry, Virtual reality, Bridging (programming), User-Computer Interface, 03 medical and health sciences, Software, Computer Graphics, biochemistry, Software tools, 030304 developmental biology, Internet, 0303 health sciences, Ubiquitin, business.industry, Systems Biology, Computational Biology, Proteins, Data science, 0104 chemical sciences, Visualization, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Snapshot (computer storage), business, Molecular Graphics
Abstract: International audience; Molecular visualisation is fundamental in the current scientific literature, textbooks and dissemination materials, forming an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Visual exploration has become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. Here we first describe a few Swiss Army knives geared towards protein visualisation for everyday use with an existing large user base, then focus on more specialised tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.; La visualisation moléculaire est fondamentale dans la littérature scientifique actuelle, les manuels et les documents de diffusion, formant un support essentiel pour présenter les résultats, raisonner et formuler des hypothèses liées à la structure moléculaire. L'exploration visuelle est devenue facilement accessible sur une grande variété de plateformes grâce à des outils logiciels avancés qui rendent un grand service à la communauté scientifique. Ces outils sont souvent développés dans toutes les disciplines reliant l'informatique, la biologie et la chimie. Ici, nous décrivons d'abord quelques couteaux de l'armée suisse axés sur la visualisation des protéines pour un usage quotidien avec une large base d'utilisateurs existante, puis nous nous concentrons sur des outils plus spécialisés pour des besoins particuliers qui ne sont pas encore aussi largement connus. Notre sélection n'est nullement exhaustive, mais reflète un aperçu diversifié de scénarios que nous considérons comme informatifs pour le lecteur. Nous terminons par un compte rendu des tendances et perspectives futures.
Published: 2020

232. Direct Homologous dsDNA–dsDNA Pairing: How, Where, and Why?

Author: Eugene Gladyshev, Tinh-Suong Nguyen, Alexey K. Mazur, Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Epigénomique fongique - Fungal Epigenomics, Institut Pasteur [Paris], ANR-11-LABX-0011,DYNAMO,Dynamique des membranes transductrices d'énergie : biogénèse et organisation supramoléculaire.(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Paris Diderot - Paris 7 (UPD7)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Group Fungal Epigenomics, Department of Mycology, Institut Pasteur
Subjects: RAD51, MSUD, DNA homology recognition, Biology, Homology (biology), 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Meiosis, Structural Biology, Sequence Homology, Nucleic Acid, dsDNAedsDNA pairing, Homologous chromosome, Base Pairing, Molecular Biology, 030304 developmental biology, Genetics, 0303 health sciences, Point mutation, Fungi, nutritional and metabolic diseases, Biomolecules (q-bio.BM), [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Recombination-independent, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Quantitative Biology - Biomolecules, chemistry, RIP, FOS: Biological sciences, Pairing, DMC1, Dimerization, 030217 neurology & neurosurgery
Abstract: The ability of homologous chromosomes (or selected chromosomal loci) to pair specifically in the apparent absence of DNA breakage and recombination represents a prominent feature of eukaryotic biology. The mechanism of homology recognition at the basis of such recombination-independent pairing has remained elusive. A number of studies have supported the idea that sequence homology can be sensed between intact DNA double helices in vivo. In particular, recent analyses of the two silencing phenomena in fungi, known as repeat-induced point mutation (RIP) and meiotic silencing by unpaired DNA (MSUD), have provided genetic evidence for the existence of the direct homologous dsDNA-dsDNA pairing. Both RIP and MSUD likely rely on the same search strategy, by which dsDNA segments are matched as arrays of interspersed base-pair triplets. This process is general and very efficient, yet it proceeds normally without the RecA/Rad51/Dmc1 proteins. Further studies of RIP and MSUD may yield surprising insights into the function of DNA in the cell., 13 pages, 2 figures, "Perspective" paper for JMB
Published: 2020

233. Temperature Unmasks Allosteric Propensity in a Thermophilic Malate Dehydrogenase via Dewetting and Collapse

Author: Marina Katava, Fabio Sterpone, Marco Maccarini, Michael Sztucki, Massimo Marchi, Dominique Madern, Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, PSL Research University, Paris 75000 France, Service de Bioénergétique, Biologie Stucturale, et Mécanismes (SB2SM), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), European Synchroton Radiation Facility [Grenoble] (ESRF), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris Diderot - Paris 7 (UPD7)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-SyNaBi ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE11-0011,AlloAnc,Allostérie Ancestrale(2016)
Subjects: [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Allosteric regulation, Working temperature, Molecular Dynamics Simulation, 010402 general chemistry, 01 natural sciences, Malate dehydrogenase, Cofactor, Molecular dynamics, Allosteric Regulation, Malate Dehydrogenase, 0103 physical sciences, Materials Chemistry, Active state, Dewetting, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, 010304 chemical physics, biology, Chemistry, Thermophile, Temperature, 0104 chemical sciences, Surfaces, Coatings and Films, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Methanocaldococcus, Biophysics, biology.protein
Abstract: In this work, we combine experiments and molecular simulations to unveil the hidden allosteric propensity of a thermophilic malate dehydrogenase protein (MDH). We provide evidence that, at its working temperature, the nonallosteric MDH takes a compact structure because of internal dewetting and reorganizes the active state toward functional conformations similar to its homologous allosteric LDHs. Moreover, a single-point mutation confers on the MDH a cooperative behavior that mimics an allosteric LDH. Our work not only demonstrates that thermophilic MDHs use temperature as an external parameter to regulate its functionality in a similar way allosteric LDHs use substrates/cofactors binding but also shows that the scaffold of MDHs possesses an intrinsic and hidden allosteric potentiality.
Published: 2020

234. Water dynamics at electrified graphene interfaces: a jump model perspective

Author: Yiwei Zhang, Damien Laage, Guillaume Stirnemann, James T. Hynes, Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), and Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Materials science, Graphene, General Physics and Astronomy, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, law.invention, Molecular dynamics, Water dynamics, 13. Climate action, Standard electrode potential, Chemical physics, law, Jump model, Jump, [CHIM]Chemical Sciences, Dynamical heterogeneity, Physical and Theoretical Chemistry, 0210 nano-technology, Electrode potential
Abstract: International audience; The reorientation dynamics of water at electrified graphene interfaces was recently shown [J. Phys. Chem. Lett. 2020, 11, 624-631] to exhibit a surprising and strongly asymmetric behavior: positive electrode potentials slow down interfacial water reorientation, while for increasingly negative potentials water dynamics first accelerates before reaching an extremum and then being retarded for larger potentials. Here we use classical molecular dynamics simulations to determine the molecular mechanisms governing water dynamics at electrified interfaces. We show that changes in water reorientation dynamics with electrode potential arise from the electrified in-terfaces' impacts on water hydrogen-bond jump exchanges, and can be quantitatively described by the extended jump model. Finally, our simulations indicate that no significant dynamical hetero-geneity occurs within the water interfacial layer next to the weakly interacting graphene electrode.
Published: 2020

235. Letter to the Editor From Cuny et al: 'Correlation of Preoperative Imaging Findings and Parathyroidectomy Outcomes Support NICE 2019 Guidance'

Author: Thomas Cuny, Pauline Romanet, David Taïeb, Frédéric Sebag, 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), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Laboratoire de Biochimie et de Biologie Moléculaire [Hôpital de la Conception - APHM], and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: Parathyroidectomy, [SDV.GEN]Life Sciences [q-bio]/Genetics, Endocrinology, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Humans, Hyperparathyroidism, Primary, Biochemistry
Abstract: International audience
Published: 2022

236. Metabolic Disorders in Patients with Chronic Hepatitis B Virus Infection: Coffee as a Panacea? (ANRS CO22 Hepather Cohort)

Author: Tangui, Barré, Hélène, Fontaine, Stanislas, Pol, Clémence, Ramier, Vincent, Di Beo, Camelia, Protopopescu, Fabienne, Marcellin, Morgane, Bureau, Marc, Bourlière, Céline, Dorival, Ventzislava, Petrov-Sanchez, Tarik, Asselah, Elisabeth, Delarocque-Astagneau, Dominique, Larrey, Jean-Charles, Duclos-Vallée, Fabrice, Carrat, Patrizia, Carrieri, On Behalf Of The Anrs/Afef Hepather Study Group, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Raymond Poincaré [AP-HP], Laboratoire de biochimie Saint-Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gilead Sciences, Meso Scale Diagnostics, MSD, Janssen Pharmaceuticals, Agence Nationale de la Recherche, ANR, Association Française pour l'Etude du Foie, AFEF, The Hepather cohort is funded by INSERM-ANRS MIE (France REcherche Nord&sud Sida-vih Hepatites|Maladies Infectieuses Emergentes), ANR Equipex and Cohort (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé) and MSD, Janssen, Gilead, Abbvie, BMS, Roche. These funding sources had no role in the writing of the manuscript, or in the decision to submit it for publication., Acknowledgments: We would like to thank the participating patients and clinicians at each site. We also thank INSERM-ANRS MIE for sponsoring, funding and conducting the ANRS CO22 Hepather cohort in collaboration with the French Association for the Study of the Liver (Association Française pour l'Etude du Foie: AFEF). Finally, our thanks to Jude Sweeney (Milan, Italy) for the English revision and copyediting of our manuscript, and HAL UVSQ, Équipe
Subjects: Polyphenol, [SDV] Life Sciences [q-bio], Dyslipidemia, Tea, [SDV]Life Sciences [q-bio], Hypertension, Hepatitis B, Coffee, Metabolic syndrome
Abstract: International audience; People living with chronic hepatitis B virus (HBV) infection are at high risk of liver disease progression, which is positively associated with metabolic disorders, but inversely associated with dyslipidemia. Diet, including dietary antioxidants, is a lever of metabolic disorder management. In particular, elevated coffee consumption is associated with different metabolic outcomes in the general population. We aimed to test whether such associations occur in HBV-infected people. Based on cross-sectional data from the ANRS CO22 Hepather cohort, we performed logistic regression models with (i) dyslipidemia, (ii) hypertension, and (iii) diabetes as outcomes, and with demographic, clinical, and socio-behavioral (including coffee consumption) data as explanatory variables. Among 4746 HBV-infected patients, drinking ≥3 cups of coffee per day was associated with a higher risk of dyslipidemia (adjusted odds ratio [95% confidence interval] 1.49 [1.10–2.00], p = 0.009) and a lower risk of hypertension (0.64 [0.50–0.82], p = 0.001). It was not associated with diabetes. Elevated coffee consumption was associated with a higher risk of dyslipidemia and a lower risk of hypertension in HBV-infected patients, two effects expected to be associated with favorable clinical outcomes. Further studies should test whether such metabolic benefits translate into reduced mortality risk in this population.
Published: 2022

237. Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe

Author: Nowotny, Hanna, Neumann, Uta, Tardy-Guidollet, Véronique, Ahmed, S Faisal, Baronio, Federico, Battelino, Tadej, Bertherat, Jérôme, Blankenstein, Oliver, Bonomi, Marco, Bouvattier, Claire, Brac de la Perrière, Aude, Brucker, Sara, Cappa, Marco, Chanson, Philippe, Claahsen-van der Grinten, Hedi L., Colao, Annamaria, Cools, Martine, Davies, Justin H., Dörr, Helmut-Günther, Fenske, Wiebke K., Ghigo, Ezio, Giordano, Roberta, Gravholt, Claus H., Huebner, Angela, Husebye, Eystein Sverre, Igbokwe, Rebecca, Juul, Anders, Kiefer, Florian W., Léger, Juliane, Menassa, Rita, Meyer, Gesine, Neocleous, Vassos, Phylactou, Leonidas A., Rohayem, Julia, Russo, Gianni, Scaroni, Carla, Touraine, Philippe, Unger, Nicole, Vojtková, Jarmila, Yeste, Diego, Lajic, Svetlana, Reisch, Nicole, Cools, Martin, Doerr, Helmuth-Guenther, Institut Català de la Salut, [Nowotny H] Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munich, Germany. [Neumann U] Centre for Chronic Sick Children, Department of Paediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Berlin, Germany. [Tardy-Guidollet V] Laboratoire de Biochimie et Biologie Moléculaire, Hospices Civils de Lyon, Centre National de Référence ‘Développement Génital: du fœtus à l’adulte DEV-GEN’ Université Lyon I, Lyon, France. [Ahmed SF] Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK. [Baronio F] Paediatric Endocrinology Unit, Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, Italy. [Battelino T] Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, University Children’s Hospital, Ljubljana, Slovenia. [Yeste D] Servei d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBERER, ISCIII, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Adrenal Hyperplasia, Congenital, Endocrinology, Diabetes and Metabolism, Malalties congènites - Tractament, Male Urogenital Diseases::Urogenital Abnormalities::Disorders of Sex Development::Adrenogenital Syndrome::Adrenal Hyperplasia, Congenital [DISEASES], Medizin, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], General Medicine, enfermedades urogenitales masculinas::anomalías urogenitales::trastornos del desarrollo sexual::síndrome adrenogenital::hiperplasia suprarrenal congénita [ENFERMEDADES], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Dexamethasone, Diabetes and Metabolism, Europe, Congenital, Endocrinology, Pregnancy, Medicine and Health Sciences, Humans, Female, Prospective Studies, Adrenal Hyperplasia, Hiperplàsia - Tractament
Abstract: Dexamethasone; Prenatal Dexametasona; Prenatal Dexametasona; Prenatal Objective To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Design and methods A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN. Results Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4–5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France. Conclusions This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH. This work was supported by the Deutsche Forschungsgemeinschaft (Heisenberg Professorship, 325768017 to N R and 314061271-TRR205 to N R and A H), the European Commission for funding EndoERN CHAFEA FPA grant no. 739527, the Eva Luise und Horst Köhler Stiftung & Else Kröner-Fresenius-Stiftung (2019_KollegSE.03 to H N) and the Stockholm County Council (Senior clinical research fellowship dnr RS 2019-1140 to S L), Stiftelsen Frimurare Barnhuset i Stockholm and Lisa and Johan Grönbergs Stiftelse.
Published: 2022

238. Reply to the letter from Gazulla et al

Author: Philippe Couratier, Mamede de Carvalho, Christian Lunetta, Patrick Vourc'h, Marie-Hélène Soriani, Susana Pinto, Philippe Corcia, Claude Desnuelle, Marta Gromicho, Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre référent Sclérose Latérale Amyotrophique et autres maladies du motoneurone [CHU Limoges] (SLA CHU Limoges), and Laboratoire de Biochimie et Biologie Moléculaire [Tours]
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Neurology, business.industry, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Theology, business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2022

239. Cumulative influence of elastin peptides and plasminogen on matrix metalloproteinase activation and type I collagen invasion by HT-1080 fibrosarcoma cells

Author: Eric HUET, Bertrand Brassart, Jean-Hubert Cauchard, Laurent Debelle, Birembaut, Philippe L., Jean Wallach, Herve Emonard, Polette, Myriam C., William Hornebeck, Université de Reims Champagne-Ardenne (URCA), Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie Analytique et Synthèse Bioorganique (LBASB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Reims Champagne-Ardenne (URCA), Laboratory of Biochemistry and Molecular Biology (LBMB), Faculty of Medicine-UPRESA 6021, Laboratoire de Biochimie et Biologie Moléculaire (LBBM), Faculté de Médecine-IFR 53 Biomolécules-UPRESA 6021, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), and Birembaut, Philippe
Subjects: MESH: DNA Primers, MESH: Enzyme Activation, Fibrosarcoma, [SDV]Life Sciences [q-bio], MESH: Collagenases, MESH: Elastin, MESH: Collagen Type I, MESH: Metalloendopeptidases, Enzyme-Linked Immunosorbent Assay, Receptors, Cell Surface, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Collagen Type I, MESH: Enzyme Precursors, MESH: Neopla, Tumor Cells, Cultured, Humans, Neoplasm Invasiveness, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Gelatinases, Collagenases, Fibrinolysin, ComputingMilieux_MISCELLANEOUS, DNA Primers, Enzyme Precursors, Tissue Inhibitor of Metalloproteinase-2, MESH: Humans, integumentary system, MESH: Fibrosarcoma, Reverse Transcriptase Polymerase Chain Reaction, Metalloendopeptidases, MESH: Enzyme-Linked Immunosorbent Assay, Plasminogen, Urokinase-Type Plasminogen Activator, Peptide Fragments, Elastin, Enzyme Activation, MESH: Matrix Metalloproteinase 2, MESH: Matrix Metalloproteinase 1, Gelatinases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Gelatin, Matrix Metalloproteinase 2, Matrix Metalloproteinase 1, MESH: Gelatin
Abstract: HT-1080 fibrosarcoma cells express at their plasma membrane the elastin-binding protein (EBP). Occupancy of EBP by elastin fragments, tropoelastin or XGVAPG peptides was found to trigger procollagenase-1 (proMMP-1) overproduction by HT-1080 cells at the protein and enzyme levels. RT-PCR analysis indicated that elastin peptides did not modify the MMP-1 mRNA steady state levels, suggesting the involvement of a post-transcriptional mechanism. We previously reported that binding of elastin peptides to EBP induced other matrix metalloproteinases (MMP-2 and MT1-MMP) expression. Since those peptides were here found to also accelerate the secretion of urokinase from HT-1080 cells, culture medium was supplemented with plasminogen together with elastin peptides at aims to induce or potentiate MMPs activation cascades. In such conditions, plasmin activity was generated and exacerbate proMMP-1 and proMMP-2 activation. As a consequence, elastin peptides and plasminogen-treated HT-1080 cells displayed a significant type I collagen matrix invasive capacity.
Published: 2002

240. Can antidepressants unlock prescription of rimonabant in the fight against COVID-19?

Author: Hugues Chap, Fabienne Briand-Mésange, Stephanie Trudel, Jérôme Ausseil, Jean-Pierre Salles, Juliette Salles, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Benson-Rumiz, Alicia
Subjects: MESH: Prescriptions, 2019-20 coronavirus outbreak, Cell biology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MESH: Rimonabant / therapeutic use, Bioinformatics, Biochemistry, Cellular and Molecular Neuroscience, Rimonabant, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Antidepressive Agents / therapeutic use, Correspondence, medicine, MESH: COVID-19, MESH: SARS-CoV-2, Medical prescription, Molecular Biology, Depression (differential diagnoses), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Depression, Drug discovery, Psychiatry and Mental health, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; We read with real enthusiasm the paper by Hoertel et al. showing an “association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19”. Their observation reinforces preliminary data of a double-blind, randomized clinical trial showing significant reduction of COVID-19 worsening in outpatients treated with fluvoxamine. By the time those promising results should obviously stimulate organization of large randomized clinical trials on the use of antidepressants in the fight against COVID-19, we want to plead for introducing rimonabant combined to an antidepressant in some of those trials as well as in preclinical studies.
Published: 2021

241. The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa

Author: Laura Gaspari, Denis Mariano-Goulart, Rémi Doré, Patrick Lefebvre, Maude Seneque, Eric Renard, Philippe Courtet, Didier Laux, Sébastien Guillaume, Pascal Philibert, Laurent Maïmoun, Krishna Kunal Mahadea, Charles Sultan, Ariane Sultan, Marie Picot, Helena Huguet, Vincent Boudousq, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), MORNET, Dominique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lapeyronie [Montpellier] (CHU), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Hôpital de la Colombière, Service de Médecine Nucléaire [Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Institut d’Electronique et des Systèmes (IES), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHRU Nîmes], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Acoustique (ACO), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Photonique et Ondes (PO), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: musculoskeletal diseases, 0301 basic medicine, medicine.medical_specialty, Heel, Areal bone mineral density (aBMD), [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Standard score, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Medicine, Orthopedics and Sports Medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Bone mineral, business.industry, Dual-X-ray absorptiometry (DXA), [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Quantitative ultrasound, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.anatomical_structure, Anorexia nervosa (differential diagnoses), Orthopedic surgery, Broadband ultrasound attenuation (BUA) bone demineralization, Amenorrhea, Quantitative ultrasound (QUS), 030101 anatomy & morphology, medicine.symptom, business, Nuclear medicine, Body mass index
Abstract: International audience; This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients.Purpose: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN).Methods: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm2) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel.Results: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm2 vs 0.806 ± 0.010 g/cm2), lumbar spine (0.966 ± 0.012 g/cm2 vs 0.886 ± 0.010 g/cm2), and radius (0.545 ± 0.005 g/cm2 vs 0.526 ± 0.04 g/cm2) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p
Published: 2021

242. Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Author: Mikaël Croyal, Matthieu Wargny, Kevin Chemello, Chloé Chevalier, Valentin Blanchard, Edith Bigot-Corbel, Gilles Lambert, Cédric Le May, Samy Hadjadj, Bertrand Cariou, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de microscopie électronique [UNIV Nantes] (SFR Santé - Hôtel Dieu), Université de Nantes (UN)-Hôtel-Dieu de Nantes-Centre hospitalier universitaire de Nantes (CHU Nantes), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Mass Spectrometry Core Facility [Nantes] (CRNH-O ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Santé publique - Clinique des données [CHU Nantes] (Pôle Hospitalo-Universitaire 11), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of British Columbia (UBC), Laboratoire de Biochimie [CHU Nantes], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], and Le May, Cedric
Subjects: Male, Time Factors, endocrine system diseases, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, Risk Assessment, Mass Spectrometry, Prediabetic State, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Risk Factors, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Diseases of the circulatory (Cardiovascular) system, Humans, Prospective Studies, Aged, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Incidence, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Type 2 diabetes, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Apolipoprotein L1, Prognosis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, IT-Diab study, New-onset diabetes, Apolipoproteins, Clusterin, Diabetes Mellitus, Type 2, RC666-701, Disease Progression, Female, Apolipoprotein E, France, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract: Background The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up. Methods In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models. Results During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (p = 0.002) compared to the middle and upper thirds. Conclusions The plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509
Published: 2021

243. GABAA Receptor Subunit Composition Drives Its Sensitivity to the Insecticide Fipronil

Author: Zineb Soualah, Antoine Taly, Christian Legros, Hélène Tricoire-Leignel, Ophélie Saulais, Claire Legendre, César Mattei, Lucille Crespin, Daniel Henrion, 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), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and TALY, Antoine
Subjects: Cerebellum, cerebellum, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Protein subunit, Xenopus, Neurosciences. Biological psychiatry. Neuropsychiatry, Inhibitory postsynaptic potential, Synapse, medicine, voltage-clamp recording, Binding site, Receptor, Original Research, fipronil, biology, GABAA receptor, Chemistry, General Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, synaptic/extrasynaptic receptor, biology.organism_classification, Cell biology, medicine.anatomical_structure, Neuroscience, RC321-571
Abstract: Fipronil (FPN) is a worldwide-used neurotoxic insecticide, targeting, and blocking GABAA receptors (GABAARs). Beyond its efficiency on insect GABAARs, FPN causes neurotoxic effects in humans and mammals. Here, we investigated the mode of action of FPN on mammalian α6-containing GABAARs to understand its inhibitory effects on GABA-induced currents, as a function of the synaptic or extrasynaptic localization of GABAARs. We characterized the effects of FPN by electrophysiology using Xenopus oocytes which were microtransplanted with cerebellum membranes or injected with α6β3, α6β3γ2S (synaptic), and α6β3δ (extrasynaptic) cDNAs. At micromolar concentrations, FPN dose-dependently inhibited cerebellar GABA currents. FPN acts as a non-competitive antagonist on ternary receptors. Surprisingly, the inhibition of GABA-induced currents was partial for extra-synaptic (α6β3δ) and binary (α6β3) receptors, while synaptic α6β3γ2S receptors were fully blocked, indicating that the complementary γ or δ subunit participates in FPN-GABAAR interaction. FPN unexpectedly behaved as a positive modulator on β3 homopentamers. These data show that FPN action is driven by the subunit composition of GABAARs—highlighting the role of the complementary subunit—and thus their localization within a physiological synapse. We built a docking model of FPN on GABAARs, which reveals two putative binding sites. This is consistent with a double binding mode of FPN on GABAARs, possibly one being of high affinity and the other of low affinity. Physiologically, the γ/δ subunit incorporation drives its inhibitory level and has important significance for its toxicity on the mammalian nervous system, especially in acute exposure.
Published: 2021

244. Fast and Interactive Positioning of Proteins within Membranes

Author: André Lanrezac, Benoist Laurent, Hubert Santuz, Nicolas Férey, Marc Baaden, Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Virtual & augmented ENvIronments for Simulation & Experiments (VENISE ), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Interaction avec l'Humain (IaH), and Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Computational Mathematics, Numerical Analysis, M. Fast interactive molecular simulation, interactive molecular simulation, Computational Theory and Mathematics, protein orientation, coarse-grained representation, lipid bilayer insertion, implicit membrane, Theoretical Computer Science
Abstract: International audience; (1) Background: We developed an algorithm to perform interactive molecular simulations (IMS) of protein alignment in membranes, allowing on-the-fly monitoring and manipulation of such molecular systems at various scales. (2) Methods: UnityMol, an advanced molecular visualization software; MDDriver, a socket for data communication; and BioSpring, a Spring network simulation engine, were extended to perform IMS. These components are designed to easily communicate with each other, adapt to other molecular simulation software, and provide a development framework for adding new interaction models to simulate biological phenomena such as protein alignment in the membrane at a fast enough rate for real-time experiments. (3) Results: We describe in detail the integration of an implicit membrane model for Integral Membrane Protein And Lipid Association (IMPALA) into our IMS framework. Our implementation can cover multiple levels of representation, and the degrees of freedom can be tuned to optimize the experience. We explain the validation of this model in an interactive and exhaustive search mode. (4) Conclusions: Protein positioning in model membranes can now be performed interactively in real time.
Published: 2022

245. Conformational Dependence of Collagenase (Matrix Metalloproteinase-1) Up-regulation by Elastin Peptides in Cultured Fibroblasts

Author: Frédéric Delacoux, Laurent Debelle, Eric Huet, Patrick F.J. Fuchs, William Hornebeck, Antonio Mario Tamburro, Bertrand Brassart, Jean Wallach, Hervé Emonard, Alain J.P. Alix, Bernard Haye, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Analytique et Synthèse Bioorganique (LBASB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Department of Translational Pharmacology, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Matrice extracellulaire et régulations cellulaires (MERC), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Biochemistry and Molecular Biology (LBMB), Faculty of Medicine-UPRESA 6021, Laboratoire de Biochimie et Biologie Moléculaire (LBBM), Faculté de Médecine-IFR 53 Biomolécules-UPRESA 6021, SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)
Subjects: Protein Conformation, Proteolysis, Receptors, Cell Surface, macromolecular substances, Pertussis toxin, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Consensus Sequence, medicine, Humans, Collagenases, RNA, Messenger, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Receptor, Protein kinase A, Molecular Biology, Cells, Cultured, 030304 developmental biology, Enzyme Precursors, 0303 health sciences, Tropoelastin, biology, medicine.diagnostic_test, integumentary system, Chemistry, Circular Dichroism, Metalloendopeptidases, Cell Biology, Fibroblasts, Ligand (biochemistry), Elastin, Up-Regulation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030220 oncology & carcinogenesis, biology.protein, Collagen, Matrix Metalloproteinase 1, Signal transduction, Peptides
Abstract: International audience; We have established that treatment of cultured human skin fibroblasts with tropoelastin or with heterogenic peptides, obtained after organo-alkaline or leukocyte elastase hydrolysis of insoluble elastin, induces a high expression of pro-collagenase-1 (pro-matrix metalloproteinase-1 (pro-MMP-1)). The identical effect was achieved after stimulation with a VGVAPG synthetic peptide, reflecting the elastin-derived domain known to bind to the 67-kDa elastin-binding protein. This clearly indicated involvement of this receptor in the described phenomenon. This notion was further reinforced by the fact that elastin peptides-dependent MMP-1 up-regulation has not been demonstrated in cultures preincubated with 1 mm lactose, which causes shedding of the elastin-binding protein and with pertussis toxin, which blocks the elastin-binding protein-dependent signaling pathway involving G protein, phospholipase C, and protein kinase C. Moreover, we demonstrated that diverse peptides maintaining GXXPG sequences can also induce similar cellular effects as a "principal" VGVAPG ligand of the elastin receptor. Results of our biophysical studies suggest that this peculiar consensus sequence stabilizes a type VIII beta-turn in several similar, but not identical, peptides that maintain a sufficient conformation to be recognized by the elastin receptor. We have also established that GXXPG elastin-derived peptides, in addition to pro-MMP-1, cause up-regulation of pro-matrix metalloproteinase-3 (pro-stromelysin 1). Furthermore, we found that the presence of plasmin in the culture medium activated these MMP proenzymes, leading to a consequent degradation of collagen substrate. Our results may be, therefore, relevant to pathobiology of inflammation, in which elastin-derived peptides bearing the GXXPG conformation (created after leukocyte-dependent proteolysis) bind to the elastin receptor of local fibroblasts and trigger signals leading to expression and activation of MMP-1 and MMP-3, which in turn exacerbate local connective tissue damage.
Published: 2001

246. Hydrolysis of glycine-containing elastin pentapeptides by LasA, a metalloelastase from Pseudomonas aeruginosa

Author: S, Vessillier, F, Delolme, J, Bernillon, J, Saulnier, J, Wallach, Bussy, Agnès, Laboratoire de Biochimie Analytique et Synthèse Bioorganique ( LBASB ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Service Central d'Analyse ( SCA ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biochimie Analytique et Synthèse Bioorganique (LBASB), Université Claude Bernard Lyon 1 (UCBL), Service Central d'Analyse (SCA), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: LasA protease, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Molecular Sequence Data, Glycine, Electrophoresis, Capillary, Metalloendopeptidases, Spectrometry, Mass, Secondary Ion, elastin, Kinetics, Bacterial Proteins, hydrolysis, Tropoelastin, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Pseudomonas aeruginosa, peptides, Humans, [ CHIM.ANAL ] Chemical Sciences/Analytical chemistry, Amino Acid Sequence, Oligopeptides
Abstract: International audience; Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in vulnerable hosts. It may produce various virulence factors including proteases. Among them, LasA possesses both elastolytic and staphylolytic (hydrolysis of pentaglycine cross-links in the cell wall peptidoglycan) activities. To understand if its elastolytic activity results from a preference for glycine-rich substrates, we studied its ability to hydrolyse the 65 pentapeptides of human tropoelastin containing at least three glycines. As demonstrated by capillary electrophoresis (CE), 22 of these peptides were hydrolysed by LasA, generally at a single peptide bond and the catalytic ratio kcat/KM was determined for most of them. The highest value was obtained for LGGGA, 59 +/- 9 min(-1) x mmol(-1) x L. The specificity of hydrolysis was elucidated by CE, liquid secondary ion mass spectrometry and, in some cases, collision activated dissociation-mass analysis of ion kinetic energy. The preferred cleavage sites are GG and GA peptide bonds, the sequence GG(cleavage site)A being especially sensitive to hydrolysis. Both positions P2 and P'2 must be occupied for hydrolysis and the presence of an amino acid in P3 (but not in P'3) significantly increases the catalytic ratio. Considering these results, about 30 GGX sequences (X: G, A or Y) of human tropoelastin could be susceptible to LasA elastolysis.
Published: 2001

247. Role of Endoproteolytic Processing in the Adhesive and Signaling Functions of αvβ5 Integrin

Author: Virginie Berthet, Véronique Rigot, Serge Champion, Francis Fouchier, José Luis, Jacques Marvaldi, Jeannine Secchi, Laboratoire de Biochimie Cellulaire, CNRS UPRESA 6032, Faculté de Pharmacie, 27 Bd J. Moulin, 13 385 Marseille Cedex 5, France., Laboratoire de Biochimie Cellulaire - CNRS UPRESA 6032, Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), and Aix Marseille Université (AMU)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Integrins, [SDV]Life Sciences [q-bio], Integrin, Biochemistry, CD49c, Collagen receptor, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Adhesion, Tumor Cells, Cultured, Animals, Humans, Receptors, Vitronectin, Vitronectin, Cell adhesion, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mitogen-Activated Protein Kinase 1, 0303 health sciences, Mitogen-Activated Protein Kinase 3, biology, Chemistry, Subtilisin, Cell Biology, Cell biology, Rats, Protein Subunits, Integrin alpha M, 030220 oncology & carcinogenesis, biology.protein, Integrin, beta 6, Signal transduction, Mitogen-Activated Protein Kinases, Protein Processing, Post-Translational, Signal Transduction
Abstract: Some integrin alpha subunits undergo a post-translational cleavage in their extracellular domain. However, the role of this cleavage in integrin function is unclear. Enzymes involved in this maturation belong to the subtilisin-like endoprotease family (convertases). To understand the role of the alpha subunit cleavage in integrin function, we have designed stable transfectants (PDX39P cells) expressing alpha(1)-PDX, a convertase inhibitor. Immunoprecipitation of cell surface proteins from PDX39P showed that alpha(3), alpha(6) and alpha(v) integrins lack endoproteolytic cleavage. We have compared adhesion between PDX39P cells and mock-transfected cells on different extracellular matrix proteins. No difference in adhesion could be observed on laminin-1 and type I collagen, while attachment of PDX39P cells to vitronectin (ligand of the alpha(v)beta(5) integrin) was dramatically reduced. The reduced adhesion of PDX39P cells was not due to changes in integrin affinity as determined by solid-phase receptor assay in a cell-free environment. Intracellular signaling pathways activated by alpha(v) integrin ligation were also affected in PDX39P cells. It thus seems that the absence of endoproteolytic cleavage of alpha(v) integrins has important consequences on signal transduction pathways leading to alterations in integrin function such as cell adhesion.
Published: 2000

248. Iron Tissue Storage and Hemoglobin Levels of Deficient Rats Repleted with Iron Bound to the Caseinophosphopeptide 1−25 of β-Casein

Author: Michel Drosdowsky, Jean-Louis Maubois, Saïd Bouhallab, Dominique Bouglé, Pierre Arhan, Nabil Ait-Oukhatar, Laboratoire de Physiologie Digestive et Nutritionnelle, Centre Hospitalier Universitaire de Caen, Chercheur indépendant, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Laboratoire de Biochimie and Service de Pe´diatrie A, Laboratoire de Biochimie and Service de Pédiatrie A, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and 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)
Subjects: Male, Iron, bioavailability, tissue storage, hemoglobin, casein, phosphopeptide, milk, protein, rat, modèle animal, digestion enzymatique, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], absorption du fer, hémoglobine, Hemoglobin levels, Rats, Sprague-Dawley, Hemoglobins, chemistry.chemical_compound, Casein, Food science, bioaccessibilité, 0303 health sciences, Chemistry, Caseins, 04 agricultural and veterinary sciences, 040401 food science, animal models, 3. Good health, medicine.anatomical_structure, Liver, Biochemistry, protéine, General Agricultural and Biological Sciences, Protein Binding, Caseinophosphopeptide 1-25, Anemia, Molecular Sequence Data, Spleen, 03 medical and health sciences, 0404 agricultural biotechnology, medicine, Animals, Amino Acid Sequence, caséine, General Chemistry, medicine.disease, lait, Peptide Fragments, Rats, Bioavailability, Phosphoserine, hemoglobinuria, Hemoglobin
Abstract: Caseinophosphopeptides (CPP) issued from enzyme digestion of caseins bind cations and keep them soluble in the digestive tract. They could be used as ligands to improve iron (Fe) bioavailability. Fe-deficient young rats were repleted with Fe (40 or 200 mg/kg of diet) bound either to the β-CN (1−25) of β-casein or to whole β-casein or as FeSO4. A control pair-fed group was given 200 mg of Fe (FeSO4)/kg of diet for 6 weeks. After repletion, hemoglobin concentration of the control group was reached only by the β-CN (1−25) animals fed 200 mg of Fe/kg; β-CN (1−25) bound Fe (40 and 200 mg) produced higher Fe liver and spleen stores than FeSO4. Binding Fe to the whole, nonhydrolyzed β-casein gave results intermediate between the other experimental groups. Binding Fe to phosphoserine residues of low molecular weight CPP improved its ability to cure anemia and to restore iron tissue stores, as compared to Fe bound to the whole casein and to inorganic salts. Keywords: Iron; bioavailability; tissue storage; hemoglob...
Published: 1999

249. Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

Author: Alba Rodríguez-García, María Linares, María Luz Morales, Sophie Allain-Maillet, Nicolas Mennesson, Ricardo Sanchez, Rafael Alonso, Alejandra Leivas, Alfredo Pérez-Rivilla, Edith Bigot-Corbel, Sylvie Hermouet, Joaquín Martínez-López, Instituto de Investigación Sanitaria Hospital 12 de Octubre [Madrid, Spain] (I2SH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Hospital Universitario 12 de Octubre [Madrid], Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHU Nantes], and Dupuis, Christine
Subjects: Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Paraproteinemias, Hepacivirus, Antibodies, Viral, Antiviral Agents, Monoclonal Gammopathy of Undetermined Significance, hepatitis (C) virus, Immunology and Allergy, Humans, Aged, Original Research, monoclonal gammopathies, Antibodies, Monoclonal, RC581-607, Middle Aged, Viral Load, Hepatitis C, antiviral, infection, [SDV] Life Sciences [q-bio], multiple myeloma, Treatment Outcome, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Disease Susceptibility, Immunologic diseases. Allergy, Biomarkers
Abstract: International audience; Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.
Published: 2021

250. When Order Meets Disorder: Modeling and Function of the Protein Interface in Fuzzy Complexes

Author: Chantal Prévost, Sophie Sacquin-Mora, Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de biologie physico-chimique (IBPC (FR_550)), and Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Protein Folding, Molecular model, Review, Molecular Dynamics Simulation, Intrinsically disordered proteins, Microbiology, 01 natural sciences, Biochemistry, 03 medical and health sciences, Molecular dynamics, 0103 physical sciences, Structural motif, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Physics, 0303 health sciences, 010304 chemical physics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], molecular modeling, fuzzy complexes, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], QR1-502, Folding (chemistry), disorder and function, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Order (biology), Nucleoproteins, intrinsically disordered proteins, Biological system, Function (biology), Macromolecule, Protein Binding
Abstract: The degree of proteins structural organization ranges from highly structured, compact folding to intrinsic disorder, where each degree of self-organization corresponds to specific functions: well-organized structural motifs in enzymes offer a proper environment for precisely positioned functional groups to participate in catalytic reactions; at the other end of the self-organization spectrum, intrinsically disordered proteins act as binding hubs via the formation of multiple, transient and often non-specific interactions. This review focusses on cases where structurally organized proteins or domains associate with highly disordered protein chains, leading to the formation of interfaces with varying degrees of fuzziness. We present a review of the computational methods developed to provide us with information on such fuzzy interfaces, and how they integrate experimental information. The discussion focusses on two specific cases, microtubules and homologous recombination nucleoprotein filaments, where a network of intrinsically disordered tails exerts regulatory function in recruiting partner macromolecules, proteins or DNA and tuning the atomic level association. Notably, we show how computational approaches such as molecular dynamics simulations can bring new knowledge to help bridging the gap between experimental analysis, that mostly concerns ensemble properties, and the behavior of individual disordered protein chains that contribute to regulation functions.
Published: 2021

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