285 results on '"C. Marcais"'
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2. Genetic heterogeneity of hepatocellular carcinoma Unsal H, Yakicier C, Marcais C, Kew M, Volkmann M, Zentgraf H, Isselbacher KJ, et al Proc Natl Acad Sci U S A 1994;91:822?826
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- 1995
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3. Involvement of a homozygous exon 6 deletion of LMF1 gene in intermittent severe hypertriglyceridemia
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Mathilde Di Filippo, Muriel Mahl, Sybil Charrière, Anne-Sophie Wozny, Oriane Marmontel, Philippe Moulin, C. Marcais, Thomas Simonet, Marine Serveaux Dancer, Sabrina Dumont, CarMeN, laboratoire, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Service de Biochimie et Biologie Moléculaire Grand Est [HCL, Lyon] (Centre de Biologie et de Pathologie), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)
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medicine.medical_specialty ,Severe hypertriglyceridemia ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,[SDV]Life Sciences [q-bio] ,Nonsense ,Pcr cloning ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Multifactorial chylomicronemia syndrome ,Humans ,030212 general & internal medicine ,Copy-number variation ,Gene ,media_common ,Sequence Deletion ,Hypertriglyceridemia ,Nutrition and Dietetics ,business.industry ,Homozygote ,Triglyceride ,Membrane Proteins ,Exons ,medicine.disease ,Phenotype ,3. Good health ,[SDV] Life Sciences [q-bio] ,Lipolysis ,Endocrinology ,Familial chylomicronemia syndrome ,Female ,Cardiology and Cardiovascular Medicine ,business ,Copy number variation ,lmf1 - Abstract
International audience; Severe hypertriglyceridemia (HTG), characterized by triglycerides (TG) permanently over 10 mmol/L, may correspond to familial chylomicronemia syndrome (FCS), a rare disorder. However, hypertriglyceridemic patients more often present multifactorial chylomicronemia syndrome (MCS), characterized by highly variable TG. A few nonsense variants of LMF1 gene were reported in literature in FCS patients. In this study, we described a woman with an intermittent severe HTG. NGS analysis and the sequencing of a long range PCR product revealed a homozygous deletion of 6507 base pairs in LMF1 gene, c.730-1528\₈98-3417del, removing exon 6, predicted to create an in-frame deletion of 56 amino acids, p.(Thr244_Gln299del). Despite an exon 6 homozygous deletion of LMF1, the patient's highly variable lipid phenotype was suggestive of MCS diagnosis.
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- 2020
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4. Characterisation of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome (MCS): Establishment of an FCS clinical diagnostic score
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Ioanna Gouni-Berthold, Handrean Soran, Laura D'Erasmo, Erik S.G. Stroes, Željko Reiner, Robert Cramb, Luis Antonio Alvarez-Sala Walther, Marcello Arca, Xavier Pintó, Claudia Stefanutti, Maurizio Averna, Robert Dufour, Colin D. Johnson, Jan Borén, Davide Noto, Philippe Moulin, Alessia Di Costanzo, Elizabeth Hughes, Eric Bruckert, C. Marcais, Angelo B. Cefalù, Maciej Banach, Jeanine E. Roeters van Lennep, Moulin, Philippe, Dufour, Robert, Averna, Maurizio, Arca, Marcello, Cefalù, Angelo B., Noto, Davide, D'Erasmo, Laura, Di Costanzo, Alessia, Marçais, Christophe, Walther, Luis Antonio Alvarez-Sala, Banach, Maciej, Borén, Jan, Cramb, Robert, Gouni-Berthold, Ioanna, Hughes, Elizabeth, Johnson, Colin, Pintó, Xavier, Reiner, Željko, van Lennep, Jeanine Roeter, Soran, Handrean, Stefanutti, Claudia, Stroes, Erik, Bruckert, Eric, Internal Medicine, ACS - Atherosclerosis & ischemic syndromes, and Vascular Medicine
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Settore MED/09 - Medicina Interna ,diagnosis ,MEDLINE ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Bioinformatics ,lcsh:Computer applications to medicine. Medical informatics ,03 medical and health sciences ,familial chylomicronaemia syndrome, diagnostic score ,0302 clinical medicine ,Diagnòstic ,Diagnosis ,Malalties hereditàries ,score ,Medicine ,lcsh:Science (General) ,Genetics, Genomics and Molecular Biology ,Multidisciplinary ,business.industry ,familial chylomicronaemia syndrome (FCS), multifactorial chylomicronaemia syndrome (MCS), diagnosis, score ,familial chylomicronaemia syndrome (FCS) ,Rare diseases ,lcsh:R858-859.7 ,lipids (amino acids, peptides, and proteins) ,Malalties rares ,chylomicronaemia syndrome ,multifactorial chylomicronaemia syndrome ,business ,multifactorial chylomicronaemia syndrome (MCS) ,Genetic diseases ,lcsh:Q1-390 - Abstract
Data presented in this article are supplementary material to our article entitled "Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recom mendations and proposal of an "FCS Score" (Moulin et al., 2018, in press). The data describe the genotypes of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicro naemia syndrome (MCS), from the validation and replication cohorts.
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- 2018
5. Quand demander un bilan génétique devant une hypertriglycéridémie ?
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Sybil Charrière, Philippe Moulin, M. Di-Filippo, A. Villard, and C. Marcais
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Gynecology ,medicine.medical_specialty ,Nutrition and Dietetics ,business.industry ,Endocrinology, Diabetes and Metabolism ,030204 cardiovascular system & hematology ,Familial hyperchylomicronemia syndrome ,03 medical and health sciences ,0302 clinical medicine ,Internal Medicine ,Medicine ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business - Abstract
Resume Les hypertriglyceridemies correspondent a un ensemble tres heterogene de dyslipidemies, aussi bien au plan phenotypique que mecanistique. En effet, elles peuvent etre isolees ou mixtes, mineures, moderees ou majeures, et combiner en proportion variable des facteurs genetiques et secondaires. Les hypertriglyceridemies sont frequentes [1] et, le plus souvent, secondaires a des facteurs environnementaux ; une exploration genetique ne doit donc pas etre systematique devant la decouverte d’une hypertriglyceridemie. La realisation de la genetique peut constituer une aide au diagnostic et a la prise en charge d’une minorite des hypertriglyceridemies. Il convient de reperer et selectionner soigneusement les indications pour ne pas generer un gaspillage d’examens genetiques important, et se retrouver confronte a une multitude de polymorphismes de susceptibilite difficile a expliquer et sans retombee clinique tangible.
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- 2016
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6. Kinetics of triglyceride decrease during hospitalisation for major hyperchylomicronemia in multifactorial chylomicronemia syndrome
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N. Bouzehouane, Sybil Charrière, Myriam Moret, P. Moulin, Delphine Collin-Chavagnac, O. Marmontel, M. Di Filippo, L. Groisne, Sylvie Villar-Fimbel, and C. Marcais
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chemistry.chemical_compound ,medicine.medical_specialty ,Endocrinology ,Triglyceride ,chemistry ,business.industry ,Internal medicine ,Kinetics ,medicine ,Cardiology and Cardiovascular Medicine ,business ,Chylomicronemia syndrome - Published
- 2020
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7. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an 'FCS score'
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Handrean Soran, Maurizio Averna, Davide Noto, Elizabeth A. Hughes, Luis Antonio Alvarez-Sala Walther, Angelo B. Cefalù, Željko Reiner, Alessia Di Costanzo, Laura D'Erasmo, Robert Dufour, Ioanna Gouni-Berthold, Erik S.G. Stroes, Jan Borén, C. Marcais, Philippe Moulin, Marcello Arca, Eric Bruckert, Xavier Pintó, Colin D. Johnson, Jeanine E. Roeters van Lennep, Maciej Banach, Robert Cramb, Claudia Stefanutti, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Department of Bioinformatics and Telemedicine, Jagiellonian University - Medical College, Jagiellonian University [Krakow] (UJ)-Jagiellonian University [Krakow] (UJ), Service d' Endocrinologie, Centre Hospitalier Universitaire de Grenoble, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ)-Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Internal Medicine, Moulin, Philippe, Dufour, Robert, Averna, Maurizio, Arca, Marcello, Cefalù, Angelo B., Noto, Davide, D'Erasmo, Laura, Di Costanzo, Alessia, Marçais, Christophe, Alvarez-Sala Walther, Luis Antonio, Banach, Maciej, Borén, Jan, Cramb, Robert, Gouni-Berthold, Ioanna, Hughes, Elizabeth, Johnson, Colin, Pintó, Xavier, Reiner, Željko, van Lennep, Jeanine Roeter, Soran, Handrean, Stefanutti, Claudia, Stroes, Erik, and Bruckert, Eric
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[SDV]Life Sciences [q-bio] ,Diagnosis tool ,population ,030204 cardiovascular system & hematology ,burden ,apoa5 ,0302 clinical medicine ,Loss of Function Mutation ,Risk Factors ,Chylomicrons ,030212 general & internal medicine ,Age of Onset ,Hypolipidemic Agents ,BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina ,Lipoprotein lipase ,plasma triglycerides ,hyperlipoproteinemia ,Prognosis ,3. Good health ,Up-Regulation ,Phenotype ,Acute pancreatitis ,lipids (amino acids, peptides, and proteins) ,Hyperlipoproteinemia Type I ,Familial chylomicronaemia syndrome ,Major hypertriglyceridaemia ,Multifactorial chylomicronaemia ,Cardiology and Cardiovascular Medicine ,Algorithms ,acute-pancreatitis ,medicine.medical_specialty ,Consensus ,hypertriglyceridemia ,etiology ,Decision Support Techniques ,Diagnosis, Differential ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Acute pancreatiti ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine ,Genotyping ,Triglycerides ,Pregnancy ,Receiver operating characteristic ,business.industry ,severe ,Reproducibility of Results ,mutations ,lipoprotein-lipase gene ,medicine.disease ,Confidence interval ,Lipoprotein Lipase ,Pancreatitis ,Cardiovascular System & Cardiology ,business ,Biomarkers - Abstract
Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of European experts provided guidance on the diagnostic strategy surrounding FCS and proposed an algorithm-based diagnosis tool for identification of these patients, which can be readily translated into practice. Features included in this FCS score comprise: severe elevation of plasma TGs (fasting TG levels \textgreater 10 mmol/L [885 mg/dL] on multiple occasions), refractory to standard TG-lowering therapies, a young age at onset, the lack of secondary factors (except for pregnancy and oral oestrogens) and a history of episodes of acute pancreatitis. Considering 53 FCS patients from three cohorts and 52 MCS patients from three cohorts, the overall sensitivity of the FCS score (\textgreater= 10) was 88% (95% confidence interval [CI]: 0.76, 0.97) with an overall specificity of 85% (95% CI: 0.75, 0.94). Receiver operating characteristic curve area was 0.91. Pragmatic clinical scoring, by standardising diagnosis, may help differentiate FCS from MCS, may alleviate the need for systematic genotyping in patients with severe HTG and may help identify high-priority candidates for genotyping. (c) 2018 The Authors. Published by Elsevier B.V.
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- 2018
8. Circulating Klotho associates with cardiovascular morbidity and mortality during hemodialysis
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Jocelyne Drai, Marie-Christine Carlier, Xavier Moreau-Gaudry, Eric Legrand, Leslie Genet, Guillaume Jean, Emilie Blond, C. Marcais, Dominique Lataillade, Emmanuelle Dantony, François Kuentz, Denis Fouque, Delphine Maucort-Boulch, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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), Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie Nutrition Dialyse, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Dialyse des Eaux Claires, AGDUC, Clinique Médicale et Pédagogique Edouard Rist, Service de Néphrologie Hémodialyse, Centre Hospitalier Ardèche Nord, Centre de Dialyse, NephroCare, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,dialyse ,[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,030232 urology & nephrology ,morbidity ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Biochemistry ,Cohort Studies ,0302 clinical medicine ,Endocrinology ,morbidité ,Prospective Studies ,Prospective cohort study ,artificial ageing ,Klotho ,Glucuronidase ,Kidney ,Middle Aged ,Prognosis ,female genital diseases and pregnancy complications ,3. Good health ,Survival Rate ,Treatment Outcome ,medicine.anatomical_structure ,Cardiovascular Diseases ,mechanical kidney ,Female ,Hemodialysis ,Adult ,medicine.medical_specialty ,Risk Assessment ,03 medical and health sciences ,Renal Dialysis ,Internal medicine ,Diabetes mellitus ,Confidence Intervals ,medicine ,Humans ,vieillissement accelere ,Renal Insufficiency, Chronic ,Klotho Proteins ,Survival rate ,Dialysis ,Aged ,Proportional Hazards Models ,business.industry ,Biochemistry (medical) ,medicine.disease ,mortality ,Logistic Models ,cardiovasculaire ,business ,mortalité ,Biomarkers ,Kidney disease - Abstract
Epub ahead of print; Background: Klotho gene was identified as an aging suppressor. In animals klotho over-expression extends lifespan and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels and during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well.Objective: We aimed to determine the consequences of a serum klotho defect on cardiovascular morbidity and mortality during chronic dialysis.Design: The ARNOGENE study was designed to prospectively follow a cohort of hemodialysis patients for 2 years without specific intervention. 769 patients were recruited and followed from the end of 2008 until January 2011. 238 patients were analysed due to a technical sample conservation issue with other samples.Results: The median serum klotho was markedly reduced, 360.4 ng/L [IQR176.5] as compared with non-dialysis chronic kidney disease patients or healthy volunteers. Patients with a serum klotho above the first quartile (≥280 ng/L) had a significantly reduced occurrence of outcome combining cardiovascular events and cardiovascular death (OR=0.39; 0.19-0.78, p=0.008) compared to patient with klotho
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- 2017
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9. Multiple microRNA regulation of lipoprotein lipase gene abolished by 3'UTR polymorphisms in a triglyceride-lowering haplotype harboring p.Ser474Ter
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Vanessa Euthine, Charlotte Cuerq, Cyrielle Caussy, Mireille Delay, Etienne Lefai, Aline Meirhaeghe, Sophie Rome, Sybil Charrière, Philippe Moulin, Mathilde Di Filippo, C. Marcais, Jean Dallongeville, Oriane Marmontel, Michel Lagarde, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Hospices Civils de Lyon (HCL), Professor Philippe Moulin received a grant from the Fondation de France (grant number 2013 38587). Cyrielle Caussy received a grant from the French Society of Endocrinology (SFE)., Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
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0301 basic medicine ,Linkage disequilibrium ,[SDV]Life Sciences [q-bio] ,Nonsense mutation ,Population ,SNP ,Single-nucleotide polymorphism ,030204 cardiovascular system & hematology ,Biology ,Transfection ,Polymorphism, Single Nucleotide ,Gene Expression Regulation, Enzymologic ,Linkage Disequilibrium ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Databases, Genetic ,Haplotype ,Humans ,Genetic Predisposition to Disease ,Allele ,education ,3' Untranslated Regions ,Genetic Association Studies ,Triglycerides ,Genetic association ,Genetics ,Hypertriglyceridemia ,Lipoprotein lipase ,education.field_of_study ,Binding Sites ,Computational Biology ,MicroRNA ,Molecular biology ,Lipids ,MicroRNAs ,030104 developmental biology ,HEK293 Cells ,Phenotype ,Diabetes Mellitus, Type 2 ,Haplotypes ,Case-Control Studies ,Cardiology and Cardiovascular Medicine ,Biomarkers - Abstract
Background Lipoprotein lipase (LPL) is a key enzyme in triglyceride (TG) metabolism. LPL gene single nucleotide polymorphisms (SNPs) are associated with TG concentrations however the functionality of many of these SNPs remains poorly understood. MicroRNAs (miR) exert post-transcriptional down-regulation and their target sequence on the 3′UTR may be altered by SNPs. We therefore investigated whether LPL 3′UTR SNPs could modulate plasma TG concentration through the alteration of miR binding-sites. Methods and results We performed genetic association studies of LPL 3′UTR SNPs with TG concentrations in 271 type 2 diabetic patients and in general population samples (2997 individuals). A specific LPL haplotype (Hap4) was associated with lower plasma TG concentration (TG-0.18, IC95% [−0.30, −0.07] mmol/L or logTG-0.13, IC95% [−0.18, −0.08], p = 4.77·10 −8 ) in the meta-analysis. Hap4 comprises seven 3′UTR SNP minor alleles and p.Ser474Ter (rs328) a well-documented nonsense mutation associated with low TG concentration although by an unknown mechanism so far. Bio-informatic studies identified several putative miRNA binding-sites on the wild-type Hap1 haplotype, lost on Hap4. Functional validation performed in HEK-293T cells using luciferase expression constructs with various LPL 3′UTR allele combinations demonstrated a binding of miR-29, miR-1277 and miR-410 on Hap1, lost on Hap4. This loss of specific miR binding-site in presence of Hap4 was independent of the allelic variation of p.Ser474Ter (rs328). Conclusions We report the regulation of LPL by the miR-29, miR-1277 and miR-410 that is lost in presence of Hap4, a specific LPL TG-lowering haplotype. Consequently p.Ser474Ter association with TG concentration could be at least partially explained by its strong linkage disequilibrium with these functional 3′UTR SNPs.
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- 2016
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10. Génétique des hypertriglycéridémies
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Philippe Moulin, Agnès Sassolas, Sybil Charrière, C. Marcais, M. Guitard-Moret, A. Decaudain, and C. Cugnet
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Abstract
Les hypertriglyceridemies (HTG) genetiques sont en apparence peu frequentes face a la multitude d’etiologies d’HTG secondaires et plus particulierement a la frequence des HTG associees au syndrome metabolique et au diabete de type 2. Neanmoins, cette impression de rarete est trompeuse, car l’hyperlipidemie combinee familiale (HCF) constitue l’une des plus communes maladies genetiques dans la population generale, avec une prevalence de 1 % chez les adultes. De plus, dans les formes apparemment secondaires, il existe frequemment des anomalies genetiques sous-jacentes qui constituent un facteur essentiel d’accentuation. Le praticien est souvent deconcerte par la presentation polymorphe de ces dyslipidemies. Il doit savoir qu’un meme genotype se traduira par une presentation phenotypique eminemment variable selon les cofacteurs environnementaux, les interactions medicamenteuses, et la modulation en parallele par d’autres variants genetiques impliques plus ou moins directement dans le metabolisme des lipoproteines. Malgre 50 annees de recherches, notre comprehension de la physiopathologie des HTG est encore imparfaite. Il reste certainement plusieurs genes cles a identifier. Ainsi, la recente identification de l’apolipoproteine (apo) AV a apporte un nouvel eclairage sur le mecanisme des hyperchylomicronemies. Cependant, 30 % de ces dernieres restent actuellement inexpliquees.
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- 2008
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11. A TG-associated minor LPL haplotype supresses miR-29 binding on LPL 3'UTR
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Philippe Moulin, Sophie Rome, J. Dallongeville, Etienne Lefai, Aline Meirhaeghe, Mireille Delay, C. Marcais, Vanessa Euthine, C. Caussy, Sybil Charrière, M. Di Filippo, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, 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, Droit et Santé, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
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0303 health sciences ,education.field_of_study ,Lipoprotein lipase ,Three prime untranslated region ,[SDV]Life Sciences [q-bio] ,Haplotype ,Population ,digestive, oral, and skin physiology ,nutritional and metabolic diseases ,MiRNA binding ,Transfection ,030204 cardiovascular system & hematology ,Biology ,Molecular biology ,03 medical and health sciences ,0302 clinical medicine ,Luciferase ,lipids (amino acids, peptides, and proteins) ,Allele ,Cardiology and Cardiovascular Medicine ,education ,030304 developmental biology - Abstract
International audience; Aim: Identification and functional study of Lipoprotein Lipase (LPL) 3'UTR polymorphisms associated with triglyceridemia and predicted to modulate miRNA binding.Methods: We sequenced LPL 3'UTR in 271 type 2 diabetic patients with documented lipid phenotypes. Haplotype analysis was performed using PHASE software. These data were validated by meta-analysis across four French general population samples. In silico analysis identified putative miRNA binding-sites created by LPL polymorphisms. Both LPL 3'UTR wild-type (WT) and variant (VAR) sequences were cloned in luciferase reporter gene plasmid. Transfection experiments in HEK293T and co-transfection with candidate miRNA-precursor was performed to study the regulation of the LPL constructs by specific miRNA.Results: A specific haplotype combining 8 LPL polymorphisms including the rs328 and 3'UTR minor alleles was found significantly associated with lower triglycerides concentration both in type 2 diabetes and in general populations. This haplotype was predicted to disrupt several miR-29 binding-sites. In vitro, the LPL-WT construct co-transfected with miR-29 showed a significant luciferase activity decrease (-25±6%, p< 0.001), whereas no difference was observed in the presence of the LPL-VAR construct. Moreover in HEK293T cells expressing endogenously miR-29, LPL-WT haplotype expression was lower compared to LPL-VAR haplotype (-32±7%, p
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- 2015
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12. Systematic assay of lipoprotein lipase activity and mass in cohort of patients with history of type V hyperlipidemia
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Séverine Nony, Sybil Charrière, O. Marmontel, C. Marcais, M. Di Filippo, P. Moulin, C. Caussy, and Agnès Sassolas
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medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Hyperlipidemia ,Cohort ,medicine ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Lipoprotein lipase activity - Published
- 2016
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13. Niemann-Pick C1 Disease: Correlations between NPC1 Mutations, Levels of NPC1 Protein, and Phenotypes Emphasize the Functional Significance of the Putative Sterol-Sensing Domain and of the Cysteine-Rich Luminal Loop
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Gilles Millat, David A. Wenger, C. Marcais, Catherine Tomasetto, Klaus Harzer, Karim Chikh, Kousaku Ohno, Marie T. Vanier, and Anthony H. Fensom
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Adult ,Male ,Adolescent ,Genotype ,Protein Conformation ,Blotting, Western ,DNA Mutational Analysis ,Molecular Sequence Data ,Biology ,medicine.disease_cause ,Gene product ,Consanguinity ,Structure-Activity Relationship ,Niemann-Pick C1 Protein ,medicine ,Genetics ,Humans ,Missense mutation ,Genetics(clinical) ,Cysteine ,Allele ,Child ,Gene ,Conserved Sequence ,Polymorphism, Single-Stranded Conformational ,Genetics (clinical) ,Niemann-Pick Diseases ,Mutation ,Membrane Glycoproteins ,Infant, Newborn ,Intracellular Signaling Peptides and Proteins ,Genetic Variation ,Infant ,Biological Transport ,Exons ,Articles ,Phenotype ,Sterols ,Cholesterol ,Child, Preschool ,Female ,NPC1 ,Carrier Proteins - Abstract
To obtain more information of the functional domains of the NPC1 protein, the mutational spectrum and the level of immunoreactive protein were investigated in skin fibroblasts from 30 unrelated patients with Niemann-Pick C1 disease. Nine of them were characterized by mild alterations of cellular cholesterol transport (the “variant” biochemical phenotype). The mutations showed a wide distribution to nearly all NPC1 domains, with a cluster (11/32) in a conserved NPC1 cysteine-rich luminal loop. Homozygous mutations in 14 patients and a phenotypically defined allele, combined with a new mutation, in a further 10 patients allowed genotype/phenotype correlations. Premature-termination–codon mutations, the three missense mutations in the sterol-sensing domain (SSD), and A1054T in the cysteine-rich luminal loop all occurred in patients with infantile neurological onset and “classic” (severe) cholesterol-trafficking alterations. By western blot, NPC1 protein was undetectable in the SSD missense mutations studied (L724P and Q775P) and essentially was absent in the A1054T missense allele. Our results thus enhance the functional significance of the SSD and demonstrate a correlation between the absence of NPC1 protein and the most severe neurological form. In the remaining missense mutations studied, corresponding to other disease presentations (including two adults with nonneurological disease), NPC1 protein was present in significant amounts of normal size, without clear-cut correlation with either the clinical phenotype or the “classic”/“variant” biochemical phenotype. Missense mutations in the cysteine-rich luminal loop resulted in a wide array of clinical and biochemical phenotypes. Remarkably, all five mutant alleles (I943M, V950M, G986S, G992R, and the recurrent P1007A) definitively correlated with the “variant” phenotype clustered within this loop, providing new insight on the functional complexity of the latter domain.
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- 2001
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14. An APOA5 3' UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site
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Sophie Rome, Cyrielle Caussy, Vanessa Euthine, Mathilde Di Filippo, Sybil Charrière, Etienne Lefai, Agnès Sassolas, Philippe Moulin, C. Marcais, Mireille Delay, Audrey Jalabert, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Societe Francaise d'Endocrinologie, Institut National de la Sante et de la Recherche Medicale, Universite Claude Bernard Lyon 1, Fondation pour le Recherche Medicale, Fondation de France, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
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Untranslated region ,Liver/metabolism ,[SDV]Life Sciences [q-bio] ,Down-Regulation ,MiRNA binding ,Apolipoproteins A/*genetics/metabolism ,030204 cardiovascular system & hematology ,Biology ,Luciferases/metabolism ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Report ,microRNA ,Genetics ,Humans ,Genetics(clinical) ,Luciferase ,Triglycerides/*blood ,Allele ,Binding site ,Luciferases ,3' Untranslated Regions ,Apolipoproteins A ,Triglycerides ,Genetics (clinical) ,Alleles ,030304 developmental biology ,0303 health sciences ,Binding Sites ,HEK 293 cells ,3' Untranslated Regions/*genetics ,Genetic Variation ,Computational Biology ,MicroRNAs/*genetics/metabolism ,Molecular biology ,MicroRNAs ,HEK293 Cells ,Liver ,Haplotypes ,Apolipoprotein A-V - Abstract
International audience; APOA5 c.*158C\textgreaterT (rs2266788), located in the 3' UTR, belongs to APOA5 haplotype 2 (APOA5*2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5*2 display reduced APOA5 expression at the posttranscriptional level. However, the functionality of this haplotype remains unclear. We hypothesized that the hypertriglyceridemic effects of APOA5*2 could involve miRNA regulation in the APOA5 3' UTR. Bioinformatic studies have identified the creation of a potential miRNA binding site for liver-expressed miR-485-5p (MIRN485-5p) in the mutant APOA5 3' UTR with the c.*158C allele. In human embryonic kidney 293T (HEK293T) cells cotransfected with an APOA5 3' UTR luciferase reporter vector and a miR485-5p precursor, c.*158C allele expression was significantly decreased. Moreover, in HuH-7 cells endogenously expressing miR-485-5p, we observed that luciferase activity was significantly lower in the presence of the c.*158C allele than in the presence of the c.*158T allele, which was completely reversed by a miR-485-5p inhibitor. We demonstrated that the rare c.*158C APOA5 allele creates a functional target site for liver-expressed miR-485-5p. Therefore, we propose that the well-documented hypertriglyceridemic effect of APOA5*2 involves an APOA5 posttranscriptional downregulation mediated by miR-485-5p.
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- 2014
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15. The hypertriglyceridemic effect of APOC3 3'UTR variant SSt1 is not mediated by a hepatic or intestinal miRNA regulation
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Marine Serveaux Dancer, C. Marcais, M. Di Filippo, C. Caussy, Sybil Charrière, and P. Moulin
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0301 basic medicine ,03 medical and health sciences ,030109 nutrition & dietetics ,Three prime untranslated region ,microRNA ,Cancer research ,Biology ,Cardiology and Cardiovascular Medicine - Published
- 2016
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16. CO-77: L'effet hypertriglycéridémiant du variant 3'UTR Sst1 de l'APOC3 n'est pas médié par une régulation impliquant un microARN hépatique ou intestinal
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Cyrielle Caussy, Philippe Moulin, Sybil Charrière, M. Dancer, and C. Marcais
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,General Medicine - Abstract
Rationnel L'apoCIII est un regulateur majeur de la triglyceridemie plasmatique. De nombreux variants du gene APOC3 sont associes a la survenue d'une hypertriglyceridemie mais leur mecanisme d'action n'est pas bien elucide en particulier pour les variants de la region 3' non codante du gene (3' UTR), dont le variant Sst1 (c.*40G>C ou rs5128). Nous avons cherche a caracteriser les variants 3'UTR de l'APOC3 et a etudier leur potentielle regulation par des microARN hepatiques ou intestinaux. Materiels et Methodes Sequencage de la region 3'UTR d'APOC3 chez 100 patients diabetiques de type 2 (DT2) presentant une hypertriglyceridemie severe (TG>15mmol/l) (groupe HTG) compares a 100 DT2 normotriglyceridemiques (groupe NTG). Identification in silico par etude bioinformatique des potentielles pertes de site de fixation de miRNA induites par les variants identifies. Etude in vitro de la fonctionnalite des interactions entre variants geniques/ miRNA dans des cellules HepG2, HuH7 et Caco transfectees avec un vecteur luciferase contenant la 3'UTR de l'APOC3 (WT vs rs5128 et/ou rs5225). Resultats Seulement 2 variants geniques situes dans l'extremite 3'UTR de l'APOC3 ont ete identifies dans les 2 groupes de patients : SstI (rs5128) et BbvI (rs5225). Seul le variant rare S2 de SSt1 est significativement associe a l'hypertriglyceridemie (frequence allelique de 19,5 % dans le groupe HTG vs 9,5 % dans le groupe NTG, p =0,0045). Le variant S2 est systematiquement associe au variant rare B2 de Bbv1. Dans l'analyse in silico, les sites de fixation de six miRNA sont predits pour etre supprimes par le variant S2 et cinq par le variant B2. Ces miRNA sont connus pour etre exprimes dans le foie, l'intestin et les modeles cellulaires utilises. In vitro, dans les cellules HepG2, HuH7 et Caco, l'activite luciferase du vecteur exprimant les variants rares S2B2 n'est cependant pas significativement differente de celui exprimant les variants sauvages S1B1. Conclusions Nos resultats ne confirment pas l'hypothese d'une regulation du variant Sst1 de l'APOC3 par un miRNA hepatique ou intestinal.
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- 2016
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17. GPIHBP1 C89F neomutation and hydrophobic C-terminal domain G175R mutation in two pedigrees with severe hyperchylomicronemia
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Cyrille Debard, Philippe Moulin, Micheline Merlin, Noël Peretti, Etienne Lefai, Sophie Bernard, C. Marcais, Sybil Charrière, Agnès Sassolas, Mathilde Di Filippo, Mireille Delay, Alain Lachaux, Institut National de la Recherche Agronomique (INRA), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Montréal - Hôpital Hôtel-Dieu, Partenaires INRAE, Centre de Biologie et de pathologie Est, Institut National de la Sante et de la Recherche Medicale, and French Society of Nutrition
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Proband ,Adult ,Male ,Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,Mutation, Missense ,CHO Cells ,030204 cardiovascular system & hematology ,Biology ,Biochemistry ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Cricetulus ,Cricetinae ,Genotype ,Chylomicrons ,Missense mutation ,Animals ,Humans ,Allele ,Apolipoproteins A ,030304 developmental biology ,Receptors, Lipoprotein ,Genetics ,0303 health sciences ,Lipoprotein lipase ,Biochemistry (medical) ,Haplotype ,GPIHBP1 ,Infant ,DNA ,Molecular biology ,Pedigree ,Lipoprotein Lipase ,Liver ,Pancreatitis ,Apolipoprotein A-V ,Mutation ,Apolipoprotein C-II ,Hyperlipoproteinemia Type I ,Carrier Proteins ,Lipoprotein - Abstract
Context: GPIHBP1 is a new endothelial binding site for lipoprotein lipase (LPL), the key enzyme for intravascular lipolysis of triglyceride-rich lipoproteins (TGRL). We have identified two new missense mutations of the GPIHBP1 gene, C89F and G175R, by systematic sequencing in a cohort of 376 hyperchylomicronemic patients without mutations on the LPL, APOC2, or APOA5 gene. Objective: Phenotypic expression and functional consequences of these two mutations were studied. Design: We performed clinical and genotypic studies of probands and their families. GPIHBP1 functional alterations were studied in CHO pgsA-745 transfected cells. Results: Probands are an adult with a homozygous G175R mutation and a child with a hemizygous C89F neomutation and a deletion of the second allele. C89F mutation was associated with a C14F signal peptide polymorphism on the same haplotype. Both patients had resistant hyperchylomicronemia, low LPL activity, and history of acute pancreatitis. In CHO pgsA-745 cells, both G175R and C14F variants reduce the expression of GPIHBP1 at the cell surface. C89F mutation is responsible for a drastic LPL-binding defect to GPIHBP1. C14F may further potentiate C89F effect. Conclusions: The emergence of hyperchylomicronemia in the generation after a neomutation further establishes a critical role for GPIHBP1 in TGRL physiopathology in humans. Our results highlight the crucial role of C65-C89 disulfide bond in LPL binding by GPIHBP1 Ly6 domain. Furthermore, we first report a mutation of the hydrophobic C-terminal domain that impairs GPIHBP1 membrane targeting.
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- 2011
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18. Modulation of phenotypic expression of APOA5 Q97X and L242P mutations
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Mathilde Charcosset, M. Guitard, Mireille Delay, Philippe Moulin, Sybil Charrière, Valérie Pruneta-Deloche, C. Marcais, S. Billon, Agnès Sassolas, L. Groisne, M. Merlin, C. Cugnet, and Sophie Bernard
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Proband ,Apolipoprotein E ,Adult ,Male ,medicine.medical_specialty ,Heterozygote ,Adolescent ,Lipolysis ,Blotting, Western ,DNA Mutational Analysis ,Biology ,medicine.disease_cause ,Compound heterozygosity ,Apolipoproteins E ,Internal medicine ,medicine ,Humans ,Child ,Apolipoproteins A ,Aged ,Genetics ,Metabolic Syndrome ,Mutation ,Apolipoprotein C-III ,Haplotype ,Homozygote ,Heterozygote advantage ,Middle Aged ,medicine.disease ,Phenotype ,Lipoprotein Lipase ,Endocrinology ,Diabetes Mellitus, Type 2 ,Haplotypes ,Apolipoprotein A-V ,Female ,Hyperlipoproteinemia Type I ,Metabolic syndrome ,Insulin Resistance ,Cardiology and Cardiovascular Medicine - Abstract
Objective: To provide phenotypic and functional data in new patients with APOA5 mutations and to identify genetic and metabolic factors influencing their phenotypic expression. Methods and results: By sequencing APOA5 gene in a cohort of 286 hyperchylomicronemic subjects, free of LPL or APOC2 mutations, we identified 4 unrelated carriers of the Q97X mutation (3 heterozygotes and 1 homozygote) and one heterozygote with a new L242P mutation. Postheparin LPL activity level was reduced by about 50% in Q97X heterozygotes and more than 90% in the Q97X homozygote, but was normal in the L242P patient after resolution of hyperchylomicronemia. Plasma apoAV was undetectable in the Q97X homozygote and in the normal range in the L242P and Q97X heterozygous carriers. In Western blot studies, the association of apoAV with plasma lipoproteins was altered in Q97X heterozygous carriers but not in the L242P carrier. Hyperchylomicronemic heterozygotes for both mutations carried an additional APOA5 variant haplotype and/or APOE variant (E2 or E4). Type 2 diabetes or metabolic syndrome were not a major phenotypic determinant. Conclusions: The L242P mutation was present in a hyperchylomicronemic proband but its causal involvement remains to be established. The Q97X mutation was clearly involved in hyperchylomicronemia with evidence of concomitant altered intravascular lipolysis, and a complete apoAV deficiency in the homozygote. The phenotypic expression variability of APOA5 mutations was mostly influenced by compound heterozygosity with APOA5 variant haplotypes plus additional genetic factors, and in a lesser extent by the metabolic environment.
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- 2008
19. Variability of phenotypic expression in patients carriers of APOE gene mutations
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M. Di Filippo, Marjorie Dumoux, Agnès Sassolas, O. Marmontel, M. Galland, C. Marcais, A. Villard, Sybil Charrière, and P. Moulin
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Apolipoprotein E ,Genetics ,Expression (architecture) ,In patient ,Biology ,Cardiology and Cardiovascular Medicine ,Phenotype - Published
- 2015
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20. [Familial hyperchylomicronemia with a new mutation of the lipoprotein lipase gene]
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A S, Causeret, A L, Souillet, C, Marcais, V, Prunetta, A, Lachaux, M, Faure, and A, Claudy
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Chromosome Aberrations ,Genetic Carrier Screening ,Lipoproteins ,Homozygote ,Wolman Disease ,Infant ,Genes, Recessive ,Exons ,Consanguinity ,Lipoprotein Lipase ,Codon, Nonsense ,Chylomicrons ,Humans ,Female ,Hyperlipoproteinemia Type I ,Polymorphism, Single-Stranded Conformational ,Chromosomes, Human, Pair 8 - Abstract
Familial hyperchylomicronemia is a rare autosomal recessive disease caused by lipoprotein lipase deficiency.A nine month-old girl presented with eruptive xanthomas revealing a familial hyperchylomicronemia. No lipoprotein lipase activity was found. DNA analysis revealed a novel homozygous non-sense mutation of the lipoprotein lipase gene at the codon 288. The parents were heterozygous carriers.Familial hyperchylomicronemia usually presents with eruptiva xanthomas, abdominal pain, pancreatic manifestation and lipemia retinalis. Papulo-nodular xanthomas occur more frequently in children as in our case. Eighty lipoprotein lipase gene mutations have been recorded to date. The gene locates on chromosome 8. Only 9 non-sense mutations have been described which lead to a truncated protein. In our case, no enzymatic activity was detected probably due to an absence of secretion of the enzyme, even though catalytic activity persisted. The homozygous carrier status leads to hyperchylomicronemia whereas the heterozygote status may lead to mixed hyperlipidemia with an increased risk of atherosclerosis. The screening of lipoprotein lipase gene mutations should be carried out in all families with hyperchylomicronemia, regardless of the presence or absence of xanthomas.
- Published
- 2002
21. PO33 - Identification de deux nouvelles mutations de GPIHBP1 responsables d’une hyperchylomicronémie majeure
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Sybil Charrière, A. Lachaux, Philippe Moulin, Agnès Sassolas, C. Marcais, Sophie Bernard, N. Peretti, and Mathilde Charcosset
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,General Medicine - Abstract
Introduction GPIHBP1 est un nouveau site de liaison endotheliale de la lipoproteine lipase (LPL), enzyme cle de la lipolyse intravasculaire des lipoproteines riches en triglycerides (LRTG). GPIHBP1 s’exprime comme la LPL dans le tissu adipeux, le foie, le muscle. Par sequencage du gene GPIHBP1 chez des patients ayant presente une hyperchylomicronemie majeure (TG > 15 mmol/l) avec activite LPL effondree ( Materiels et methodes L’objectif de cette etude est la caracterisation fonctionnelle in vitro de ces deux mutations par transfection transitoire des formes sauvage (WT) et mutees de GPIHBP1 dans le modele cellulaire CHO745, avec etude en Western Blot de l’expression de la proteine a la surface cellulaire et de la liaison de la LPL a GPIHBP1. Resultats L’expression des formes mutees de GPIHBP1 a la surface cellulaire est diminuee : −53 ± 6.4 % pour C14F, − 35 ± 13 % pour C89F, − 45 ± 12 % pour l’haplotype C14F/C89F, et − 48 ± 7 % pour G175R, versus WT. La fixation de la LPL sur GPIHBP1 est conservee pour C14F, mais est alteree pour C89F (− 78 ± 13 %), l’haplotype C14F/C89F (− 91 ± 5 %) et pour G175R (− 43 ± 13 %), versus WT. Discussion Ces 2 nouvelles mutations de GPIHBP1 entrainent a la fois une diminution de l’expression de la proteine a la surface cellulaire et de la liaison de la LPL, avec une association synergique entre la mutation C89F et le polymorphisme C14F responsable d’une alteration majeure de liaison de la LPL. La mutation G175R est la premiere mutation decrite du domaine C terminal de la proteine implique dans la liaison au groupement GPI anchor de la proteine. Ces travaux confirment le role majeur de GPIHBP1 dans la lipolyse intravasculaire des LRTG chez l’homme.
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- 2011
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22. Ex vivo measurement of lipoprotein lipase-dependent very low density lipoprotein (VLDL)-triglyceride hydrolysis in human VLDL: an alternative to the postheparin assay of lipoprotein lipase activity?
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V, Pruneta, D, Autran, G, Ponsin, C, Marcais, L, Duvillard, B, Verges, F, Berthezene, and P, Moulin
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Adult ,Male ,Heterozygote ,Heparin ,Hydrolysis ,Homozygote ,Fatty Acids, Nonesterified ,Lipoproteins, VLDL ,Middle Aged ,Kinetics ,Lipoprotein Lipase ,Diabetes Mellitus, Type 2 ,Reference Values ,Humans ,Female ,Triglycerides ,Apolipoproteins B - Abstract
The plasma lipolysis of triglyceride (TG)-rich lipoproteins is mainly due to the activity of lipoprotein lipase (LPL). Albeit important for our analysis of certain physiopathological situations, the determination of the magnitude of LPL-dependent lipolysis is not easy to perform. This essentially results from the binding of LPL to the luminal surface of vascular endothelium. The measurements of the whole putative LPL activity have been achieved after injection of heparin, a procedure that releases LPL from endothelium. However, the physiopathological relevance of this postheparin lipolysis assay (PHLA) remains questionable because it has never been demonstrated that the bulk of endothelium-bound LPL was active. It has been recently shown that a small part of LPL is associated to circulating lipoproteins in nonheparinized plasma, raising the possibility that the lipolysis mediated by this circulating LPL might reflect the overall LPL-dependent TG hydrolysis in plasma. To address this question, we developed a new lipolysis assay in which the very low density lipoprotein (VLDL)-bound LPL-dependent VLDL-TG hydrolysis (LVTH) was directly determined through the measurement of nonesterified fatty acid (NEFA) release during in vitro incubations. LVTH measurements were performed in control subjects, in type 2 diabetics, and in either heterozygous or homozygous LPL-deficient patients. In the latter group, LVTH values were extremely low. Those of heterozygous patients and of diabetics were similarly decreased by about 40% with respect to control group. Plasma TG concentrations exhibited an inverse relationship with LVTH level. In a subgroup of subjects, LVTH and PHLA were positively correlated and the inverse correlation of LVTH with plasma or VLDL-TG concentration was stronger than that obtained with PHLA. To further study the validity of this new assay, we measured LVTH in nine subjects who were studied for their catabolism of VLDL labeled with stable isotope. No relation was observed between the direct hepatic removal of VLDL and LVTH, whereas the latter was strikingly correlated with the rate of conversion of VLDL to intermediary density lipoprotein. Collective consideration of these findings strongly suggests that LVTH is a physiologically relevant index which could advantageously replace the measurements of PHLA in numerous physiopathological situations.
- Published
- 2001
23. P1029 Influence du diabète de type 2 chez les patients dysbétalipoprotéinémiques
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Agnès Sassolas, M. Di Filippo, Sybil Charrière, A. Garon, C. Marcais, and Philippe Moulin
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,General Medicine - Abstract
Objectif Les dysbetalipoproteinemies (type III, classification de Frederikson) sont des dyslipidemies primitives rares, lors desquelles les diabetiques de type 2 (DT2) sont surrepresentes (10 a 30 % des series). Pour preciser l’interaction entre ces pathologies nous avons compare dans une cohorte de malades dysbetalipoproteinemiques, ceux presentant un DT2 et ceux indemnes de diabete, et considere la survenue de decompensation en hypertriglyceridemie majeure (> 15 mmol/L) de type V (HTGM). Materiels et methodes Etude cas-temoin retrospective de 24 patients dysbetalipoproteinemiques. Nous avons etudie les parametres cliniques (IMC, âge, sexe), biologiques (triglyceridemie, cholesterolemie, HDL, LDL, apoB, genotypage apoE), les marqueurs phenotypiques diagnostiques (CT-VLDL (mmol/L)/Tg-total (mmol/L) > 0,30, CT-VLDL (mmol/L)/Tg-VLDL (mmol/L) > 0,40 et apoB (g/L)/CT (mmol/L) Resultats Les patients diabetiques (n = 12) sont plus âges que les non diabetiques (n = 12) : 65,7 ± 14,6 ans vs 50,1 ± 14,6 ans, p = 0,005, mais sont comparables en termes de sexe (60 % d’hommes) et d’IMC (29,7 ± 4,5 kg/m 2 ). La proportion de decompensation est similaire chez les diabetiques (3/12) et les non diabetiques (5/12), p = 0,6. Le phenotype lipidique est similaire. Les ratios diagnostiques de dysbetalipoproteinemie fonctionnent pour les patients diabetiques et non diabetiques. Cependant le ratio CT-VLDL/Tg-total en periode de suivi est moins eleve chez les patients diabetiques, mais reste valable (0,32 ± 0,09 vs 0,43 ± 0,13, p = 0,04). La prevalence des facteurs environnementaux de decompensation et celle des variants genetiques de susceptibilite aux hypertriglyceridemies sont similaires. Le polymorphisme C14F du gene GPIHBP1 est retrouve uniquement chez les diabetiques (n = 4, p = 0,09), 2/3 des patients diabetiques presentant une HTGM sont porteurs de ce polymorphisme, ce resultat est non significatif en raison des faibles effectifs. Conclusion Les patients dysbetalipoproteinemiques diabetiques sont comparables aux patients non diabetiques. Le DT2 n’apparait pas comme un facteur de risque preponderant de decompensation en HTGM. Les methodes diagnostiques habituellement utilisees demeurent fiables meme en presence d’un DT2.
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- 2013
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24. P074 Facteurs de prédisposition aux pancréatites aigues au cours d’une poussée d’hypertriglycéridémie majeure
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S. Villar Fimbel, C. Marcais, S. Charrierre, C. Cugnet Anceau, A. Weber, Agnès Sassolas, C. Mezzaroba, L. Groisne, M. Moret, F. Cabet, M. Di Filippo, P. Moulin, and N. Meddour
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Medicine (miscellaneous) - Published
- 2011
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25. CO04 - L’apo av tronquée, une cause d’hypertriglycéridémie majeure dominante : l’apo av lyon
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L. Pruneta, M. Merlin, C. Marcais, Sybil Charrière, P. Moulin, V. Pruneta, S. Billon, E. Rubin, V. Durlach, Agnès Sassolas, L. Pennachio, J. Fruchart-Najib, and B. Vergès
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,General Medicine - Published
- 2004
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26. Mechanisms governing bystander activation of T cells.
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Yosri, Mohammed, Dokhan, Mohamed, Aboagye, Elizabeth, Al Moussawy, Mouhamad, and Abdelsamed, Hossam A.
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IMMUNOLOGICAL tolerance ,T cells ,PEPTIDES ,IMMUNE system ,IMMUNE response - Abstract
The immune system is endowed with the capacity to distinguish between self and non-self, so-called immune tolerance or "consciousness of the immune system." This type of awareness is designed to achieve host protection by eliminating cells expressing a wide range of non-self antigens including microbial-derived peptides. Such a successful immune response is associated with the secretion of a whole spectrum of soluble mediators, e.g., cytokines and chemokines, which not only contribute to the clearance of infected host cells but also activate T cells that are not specific to the original cognate antigen. This kind of non-specific T-cell activation is called "bystander activation." Although it is well-established that this phenomenon is cytokine-dependent, there is evidence in the literature showing the involvement of peptide/MHC recognition depending on the type of T-cell subset (naive vs. memory). Here, we will summarize our current understanding of the mechanism(s) of bystander T-cell activation as well as its biological significance in a wide range of diseases including microbial infections, cancer, auto- and alloimmunity, and chronic inflammatory diseases such as atherosclerosis. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Hyperresponsiveness of Corticoid-Resistant Th17/Tc-17 Cells to TLR-2 and TLR-4 Ligands is a Feature of Multiple Sclerosis Patients at Higher Risk of Therapy Failure.
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Hygino, Joana, Sales, Marisa C, Sacramento, Priscila M, Kasahara, Taissa M, Silva, Júlio César Costa da, Bilhão, Rafaela, Andrade, Regis M, Vasconcelos, Cláudia Cristina Ferreira, and Bento, Cleonice AM
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MONONUCLEAR leukocytes ,T helper cells ,T cells ,TOLL-like receptor agonists ,BRAIN damage - Abstract
Purpose: The presence of T cells expressing TLR-2 and TLR-4 has been associated with relapsing-remitting multiple sclerosis (RRMS) pathogenesis. Here, we evaluated whether the effectiveness of DMT in controlling clinical activity of the disease would be associated with modulation of proportion of TLRs
+ T cells. Patients and Methods: Whole peripheral blood mononuclear cells, purified CD4+ and CD8+ T cells from RRMS patients were cultured with different stimuli. The frequency of IL-17-secreting CD4+ and CD8+ T cells positive for TLR-2 and TLR-4 was determined by flow cytometry. The cytokine profile of these T cells following TLR-2 and TLR-4 stimulation was determined by Multiplex. Some of these T cell cultures were treated with hydrocortisone. The levels of LPS-binding protein (LBP) were dosed by ELISA. Clinical (occurrence of relapses) and radiological (number of active brain lesions) activity were evaluated during the 1-year follow-up. Results: Despite DMT, high intensity of TLR-2 and TLR-4 expression on (CD4+ and CD8+ ) T-cells, as well as the frequency of IL-17-secreting (CD4+ and CD8+ ) T-cells, are predictive of future RRMS relapses. Moreover, higher cytokine production related to Th17/Tc-17 phenotypes in response to TLR-2 and TLR-4 agonists was observed in DMT-treated patients and displayed an elevated number of brain lesions. The hyperresponsiveness of MS-derived T-cells to TLR-2 and TLR-4 ligands, with high levels of IL-1β, IL-6, IL-17, IFN-γ and GM-CSF in response to both TLR agonists, positively correlated with plasma LBP levels. Interestingly, corticoid was less efficient in reducing Th17 and Tc-17 cytokine production induced by TLR-2 and TLR-4 ligands in DMT-treated patients who relapsed during follow-up. Conclusion: Collectively, the data suggested that persistence of circulating Th17 and Tc17 cells expressing elevated levels of functional TLR-2 and TLR-4 could indicate high disease activity and lower therapeutic efficacy in RRMS patients. [ABSTRACT FROM AUTHOR]- Published
- 2024
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28. Niemann-Pick C1 Disease: The I1061T Substitution Is a Frequent Mutant Allele in Patients of Western European Descent and Correlates with a Classic Juvenile Phenotype
- Author
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Peter G. Pentchev, Gilles Millat, Kousaku Ohno, Jill A. Morris, Toshiyuki Yamamoto, Mohammad A. Rafi, C. Marcais, Marie T. Vanier, and David A. Wenger
- Subjects
Adult ,Male ,NPC1 gene ,Adolescent ,Genetic counseling ,DNA Mutational Analysis ,Molecular Sequence Data ,Hepatosplenomegaly ,Hispanic ,Biology ,Compound heterozygosity ,European ,Niemann-Pick C1 Protein ,Niemann-Pick C disease ,Genotype ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Allele ,Child ,Alleles ,Polymorphism, Single-Stranded Conformational ,Genetics (clinical) ,Niemann-Pick Diseases ,Membrane Glycoproteins ,Base Sequence ,Intracellular Signaling Peptides and Proteins ,Proteins ,Cholesterol, LDL ,Articles ,Fibroblasts ,medicine.disease ,Phenotype ,Child, Preschool ,Mutation (genetic algorithm) ,Mutation ,Genotype/phenotype correlation ,Female ,medicine.symptom ,Carrier Proteins ,Niemann–Pick disease ,Polymorphism, Restriction Fragment Length ,Founder effect - Abstract
Summary Niemann-Pick type C (NPC) disease is an autosomal recessive lipid-storage disorder usually characterized by hepatosplenomegaly and severe progressive neurological dysfunction, resulting from mutations affecting either the NPC1 gene (in 95% of the patients) or the yet-to-be-identified NPC2 gene. Our initial study of 25 patients with NPC1 identified a T 3182 →C transition that leads to an I1061T substitution in three patients. The mutation, located in exon 21, affects a putative transmembrane domain of the protein. PCR-based tests with genomic DNA were used to survey 115 unrelated patients from around the world with all known clinical and biochemical phenotypes of the disease. The I1061T allele constituted 33 (14.3%) of the 230 disease-causing alleles and was never found in controls (>200 alleles). The mutation was particularly frequent in patients with NPC from Western Europe, especially France (11/62 alleles) and the United Kingdom (9/32 alleles), and in Hispanic patients whose roots were in the Upper Rio Grande valley of the United States. The I1061T mutation originated in Europe and the high frequency in northern Rio Grande Hispanics results from a founder effect. All seven unrelated patients who were homozygous for the mutation and their seven affected siblings had a juvenile-onset neurological disease and severe alterations of intracellular LDL-cholesterol processing. The mutation was not found (0/40 alleles) in patients with the severe infantile neurological form of the disease. Testing for this mutation therefore has important implications for genetic counseling of families affected by NPC.
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29. A Comprehensive Review of Climate Change and Plant Diseases in Brazil.
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Angelotti, Francislene, Hamada, Emília, and Bettiol, Wagner
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MEDICAL climatology ,ENVIRONMENTAL degradation ,AGRICULTURE ,MYCOSES ,GLOBAL warming - Abstract
Analyzing the impacts of climate change on phytosanitary problems in Brazil is crucial due to the country's special role in global food security as one of the largest producers of essential commodities. This review focuses on the effects of climate change on plant diseases and discusses its main challenges in light of Brazil's diverse agricultural landscape. To assess the risk of diseases caused by fungi, bacteria, viruses, oomycetes, nematodes, and spiroplasms, we surveyed 304 pathosystems across 32 crops of economic importance from 2005 to 2022. Results show that diseases caused by fungi account for 79% of the pathosystems evaluated. Predicting the occurrence of diseases in a changing climate is a complex challenge, and the continuity of this work is strategic for Brazil's agricultural defense. The future risk scenarios analyzed here aim to help guide disease mitigation for cropping systems. Despite substantial progress and ongoing efforts, further research will be needed to effectively prevent economic and environmental damage. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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30. Phytophthora Communities Associated with Agathis australis (kauri) in Te Wao Nui o Tiriwa/Waitākere Ranges, New Zealand.
- Author
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Hunter, Shannon, Horner, Ian, Hosking, Jack, Carroll, Ellena, Newland, Jayne, Arnet, Matthew, Waipara, Nick, Burns, Bruce, Scott, Peter, and Williams, Nari
- Subjects
PHYTOPHTHORA ,PHYTOPHTHORA cinnamomi ,FOREST health ,SOIL sampling ,DIEBACK - Abstract
Studies of Phytophthora impact in forests generally focus on individual species without recognition that Phytophthora occur in multispecies communities. This study investigated community structure of Phytophthora species in the rhizosphere of Agathis australis (kauri) in Te Wao Nui o Tiriwa/Waitākere Ranges, New Zealand, in the context of kauri dieback disease expression. Soil sampling and tree monitoring were conducted on 767 randomly selected mature kauri trees. Phytophthora species were detected using both soil baiting and DNA metabarcoding of environmental DNA (eDNA). Four species were detected with soil baiting (P. agathidicida, P. cinnamomi, P. multivora, and P. pseudocryptogea/P. cryptogea) and an additional three species with metabarcoding (P. kernoviae, P. cactorum/P. aleatoria and an unknown clade 7 species). Phytophthora cinnamomi was the most abundant species and was distributed throughout the forest. Both P. multivora and P. agathidicida were limited to forest edges, suggesting more recent introductions. P. agathidicida presence was strongly correlated with declining canopy health, confirming its role as the main driver of kauri dieback. The limited distribution of P. agathidicida and infrequent detections (11.0% samples) suggests that that this species is spreading as an introduced invasive pathogen and provide hope that with strategic management (including track upgrades and closures, restricting access to uninfected areas, and continual monitoring) uninfected areas of the forest can be protected. The frequent detections of P. cinnamomi and P. multivora from symptomatic trees in the absence of P. agathidicida suggest more research is needed to understand their roles in kauri forest health. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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31. Diaporthe Species on Palms: Molecular Re-Assessment and Species Boundaries Delimitation in the D. arecae Species Complex.
- Author
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Pereira, Diana S., Hilário, Sandra, Gonçalves, Micael F. M., and Phillips, Alan J. L.
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PHYLOGEOGRAPHY ,REPRODUCTIVE isolation ,PALMS ,CLIMATE change ,NUMBERS of species ,GENETIC variation ,POISSON processes - Abstract
Due to cryptic diversification, phenotypic plasticity and host associations, multilocus phylogenetic analyses have become the most important tool in accurately identifying and circumscribing species in the Diaporthe genus. However, the application of the genealogical concordance criterion has often been overlooked, ultimately leading to an exponential increase in novel Diaporthe spp. Due to the large number of species, many lineages remain poorly understood under the so-called species complexes. For this reason, a robust delimitation of the species boundaries in Diaporthe is still an ongoing challenge. Therefore, the present study aimed to resolve the species boundaries of the Diaporthe arecae species complex (DASC) by implementing an integrative taxonomic approach. The Genealogical Phylogenetic Species Recognition (GCPSR) principle revealed incongruences between the individual gene genealogies. Moreover, the Poisson Tree Processes' (PTPs) coalescent-based species delimitation models identified three well-delimited subclades represented by the species D. arecae, D. chiangmaiensis and D. smilacicola. These results evidence that all species previously described in the D. arecae subclade are conspecific, which is coherent with the morphological indistinctiveness observed and the absence of reproductive isolation and barriers to gene flow. Thus, 52 Diaporthe spp. are reduced to synonymy under D. arecae. Recent population expansion and the possibility of incomplete lineage sorting suggested that the D. arecae subclade may be considered as ongoing evolving lineages under active divergence and speciation. Hence, the genetic diversity and intraspecific variability of D. arecae in the context of current global climate change and the role of D. arecae as a pathogen on palm trees and other hosts are also discussed. This study illustrates that species in Diaporthe are highly overestimated, and highlights the relevance of applying an integrative taxonomic approach to accurately circumscribe the species boundaries in the genus Diaporthe. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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32. 17p13 (TP53) Deletions Are Associated With an Aggressive Phenotype but Unrelated to Patient Prognosis in Urothelial Bladder Carcinomas.
- Author
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Kluth M, Hitzschke M, Furlano K, Plage H, Hofbauer S, Weinberger S, Ralla B, Fendler A, de Martino M, Roßner F, Schallenberg S, Elezkurtaj S, Lennartz M, Marx AH, Samtleben H, Fisch M, Rink M, Slojewski M, Kaczmarek K, Ecke T, Koch S, Adamini N, Weischenfeldt J, Klatte T, Minner S, Simon R, Sauter G, Schlomm T, Horst D, and Zecha H
- Subjects
- Humans, Prognosis, Male, Female, In Situ Hybridization, Fluorescence, Aged, Middle Aged, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology, Chromosomes, Human, Pair 17 genetics, Phenotype, Tumor Suppressor Protein p53 genetics, Chromosome Deletion
- Abstract
17p13 deletions including TP53 and other genes represent a common cause for reduced/lost p53 function in tumor cells. In this study, we analyzed the impact of 17p13 (TP53) deletions and p53 expression on tumor aggressiveness and patient prognosis in urothelial carcinoma. The 17p13 copy number status was analyzed by fluorescence in situ hybridization (FISH) on more than 2700 urothelial bladder carcinomas in a tissue microarray format. 17p13 deletion data were compared to p53 expression data measured by immunohistochemistry (IHC) in a previous study. Different types of p53 alterations were compared with tumor phenotype and clinical outcome data. Deletions of 17p13 occurred in 23% of 2185 analyzable carcinomas. The fraction of tumors with 17p13 deletions increased from pTa G2 low (9%) to pTa G3 (24%, p < 0.0001). In muscle-invasive carcinomas, 17p13 deletions were associated with advanced pT stage (p = 0.0246), but unrelated to patient prognosis (p > 0.5). 17p13 deletions were significantly related to p53 immunostaining (p = 0.0375). 17p13 deletions were most common in tumors with complete lack of p53 staining (31%), which supports the concept that many of these tumors have a complete loss of p53 function (p53 null phenotype). 17p13 deletions were also increased in tumors with high p53 staining (25%). In conclusion, 17p13 deletions were most commonly seen in p53 negative cancers, supporting their role as a cause for the p53 null phenotype in urothelial cancer. The association of 17p13 deletions with high grade and advanced pT stage may reflect increasing genomic instability going along with stage and grade progression., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)
- Published
- 2024
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33. Does Human Papillomavirus Play a Causative Role in Prostate Cancer? A Systematic Review Using Bradford Hill's Criteria.
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Opeyemi Bello, Ridwan, Willis-Powell, Lily, James, Olivia, Sharma, Avyay, Marsh, Elizabeth, Ellis, Libby, Gaston, Kevin, and Siddiqui, Yusra
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TRANSMISSION of papillomavirus diseases ,ONLINE information services ,PAPILLOMAVIRUSES ,SYSTEMATIC reviews ,DISEASE incidence ,RISK assessment ,PAPILLOMAVIRUS diseases ,RESEARCH funding ,MEDLINE ,POLYMERASE chain reaction ,COLLECTION & preservation of biological specimens ,PROSTATE tumors ,ONCOGENIC viruses ,DISEASE risk factors ,DISEASE complications - Abstract
Simple Summary: Prostate cancer is a major cause of cancer-related deaths globally, yet its causes remain unclear. While human papillomavirus (HPV) is known to be associated with other cancers, such as cervical cancer and anal cancer, investigation of its connection to prostate cancer has yielded mixed results. This systematic review aimed to assess the relationship between HPV and prostate cancer using Bradford Hill's criteria. Out of 482 studies screened from PubMed, 60 were included and evaluated. Although the strength of association was not strong and certain criteria were not met, the review identified plausible biological mechanisms and reported the presence of HPV in prostate cancer tissues. However, the overall quality of evidence remains low, and further high-quality studies are needed to establish a definitive link. These findings have implications for understanding prostate cancer and guiding future research efforts. Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related mortality rate. However, the aetiology of this disease is not yet fully understood. While human papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancers, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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34. Can species distribution models be used for risk assessment analyses of fungal plant pathogens? A case study with three Botryosphaeriaceae species.
- Author
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Batista, Eduardo, Lopes, Anabela, Miranda, Pedro, and Alves, Artur
- Abstract
Fungal species of the family Botryosphaeriaceae are distributed worldwide and are known important pathogens of a wide variety of forestry and agricultural plant hosts. The role of global changes impacts, especially climate change, on Botryosphaeriaceae-related diseases is still poorly understood. We mapped suitable areas for three Botryosphaeriaceae species, according to three different Shared Socio-economic Pathways (SSP) 126, 370 and 585 in different time slots: a historical climate series from 1970 to 2000 and two future projections 2021–2040 and 2081–2100. An overall increase of suitable areas for these pathogens is predicted in most of the studied scenarios. Also a possible range expansion is predicted in the northern hemisphere for Botryosphaeria dothidea and Neofusicoccum parvum. A consistent increase in the number of month with optimal growth conditions was found in most of the north hemisphere. This increase could impact on the phenology of these organisms and result in more frequent and intensive outbreaks. In this study, we explored the advantages and limitations of species distribution models, SDMs, to provide input data for Botryosphaeriaceae-related risk assessment and to improve our understanding of the ecological niche requirements of these species. A worldwide risk assessment was performed to categorise different risk levels based on current and future suitability of geographical areas to these organisms. The ability to predict plant pathogen occurrence in space and time with species distribution models at local or global scale can help decision-makers to develop management strategies to prevent or minimize the impact of future disease outbreaks. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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35. Non-invasive molecular biomarkers for monitoring solid organ transplantation: A comprehensive overview.
- Author
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Fernando JJ, Biswas R, and Biswas L
- Subjects
- Humans, Transplantation, Homologous, Graft Rejection genetics, Antibodies, Biomarkers, Graft Survival, HLA Antigens genetics, Organ Transplantation
- Abstract
Solid organ transplantation is a life-saving intervention for individuals with end-stage organ failure. Despite the effectiveness of immunosuppressive therapy, the risk of graft rejection persists in all viable transplants between individuals. The risk of rejection may vary depending on the degree of compatibility between the donor and recipient for both human leucocyte antigen (HLA) and non-HLA gene-encoded products. Monitoring the status of the allograft is a critical aspect of post-transplant management, with invasive biopsies being the standard of care for detecting rejection. Non-invasive biomarkers are increasingly being recognized as valuable tools for aiding in the detection of graft rejection, monitoring graft status and evaluating the efficacy of immunosuppressive therapy. Here, we focus on the importance of molecular biomarkers in solid organ transplantation and their potential role in clinical practice. Conventional molecular biomarkers used in transplantation include HLA typing, detection of anti-HLA antibodies, killer cell immunoglobulin-like receptor genotypes, and anti-MHC class 1-related chain A antibodies, which are important for assessing the compatibility of the donor and recipient. Emerging molecular biomarkers include the detection of donor-derived cell-free DNA, microRNAs (regulation of gene expression), exosomes (small vesicles secreted by cells), and kidney solid organ response test, in the recipient's blood for early signs of rejection. This review highlights the strengths and limitations of these molecular biomarkers and their potential role in improving transplant outcomes., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
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36. The Regulation of Triacylglycerol Metabolism and Lipoprotein Lipase Activity.
- Author
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Wen, Yi, Chen, Yan Q., and Konrad, Robert J.
- Subjects
LIPOPROTEIN lipase ,METABOLIC regulation ,APOLIPOPROTEIN C ,APOLIPOPROTEINS ,ANGIOPOIETIN-like proteins ,ADIPOSE tissues - Abstract
Triacylglycerol (TG) metabolism is tightly regulated to maintain a pool of TG within circulating lipoproteins that can be hydrolyzed in a tissue‐specific manner by lipoprotein lipase (LPL) to enable the delivery of fatty acids to adipose or oxidative tissues as needed. Elevated serum TG concentrations, which result from a deficiency of LPL activity or, more commonly, an imbalance in the regulation of tissue‐specific LPL activities, have been associated with an increased risk of atherosclerotic cardiovascular disease through multiple studies. Among the most critical LPL regulators are the angiopoietin‐like (ANGPTL) proteins ANGPTL3, ANGPTL4, and ANGPTL8, and a number of different apolipoproteins including apolipoprotein A5 (ApoA5), apolipoprotein C2 (ApoC2), and apolipoprotein C3 (ApoC3). These ANGPTLs and apolipoproteins work together to orchestrate LPL activity and therefore play pivotal roles in TG partitioning, hydrolysis, and utilization. This review summarizes the mechanisms of action, epidemiological findings, and genetic data most relevant to these ANGPTLs and apolipoproteins. The interplay between these important regulators of TG metabolism in both fasted and fed states is highlighted with a holistic view toward understanding key concepts and interactions. Strategies for developing safe and effective therapeutics to reduce circulating TG by selectively targeting these ANGPTLs and apolipoproteins are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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37. Comparison of Primers for the Detection of Phytophthora (and Other Oomycetes) from Environmental Samples.
- Author
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Burgess, Treena I., White, Diane, and Sapsford, Sarah J.
- Subjects
ENVIRONMENTAL sampling ,OOMYCETES ,COMMUNITIES ,PHYTOPATHOGENIC microorganisms ,PHYTOPHTHORA ,CITIES & towns ,INTERNAL auditing - Abstract
Many oomycetes are important plant pathogens that cause devastating diseases in agricultural fields, orchards, urban areas, and natural ecosystems. Limitations and difficulties associated with isolating these pathogens have led to a strong uptake of DNA metabarcoding and mass parallel sequencing. At least 21 primer combinations have been designed to amplify oomycetes, or more specifically, Phytophthora species, from environmental samples. We used the Illumina sequencing platform to compare 13 primer combinations on mock communities and environmental samples. The primer combinations tested varied significantly in their ability to amplify Phytophthora species in a mock community and from environmental samples; this was due to either low sensitivity (unable to detect species present in low concentrations) or a lack of specificity (an inability to amplify some species even if they were present in high concentrations). Primers designed for oomycetes underestimated the Phytophthora community compared to Phytophthora-specific primers. We recommend using technical replicates, primer combinations, internal controls, and a phylogenetic approach for assigning a species identity to OTUs or ASVs. Particular care must be taken if sampling substrates where hybrid species could be expected. Overall, the choice of primers should depend upon the hypothesis being tested. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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38. Toll-like receptor-mediated innate immunity orchestrates adaptive immune responses in HBV infection.
- Author
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Yanqin Du, Jun Wu, Jia Liu, Xin Zheng, Dongliang Yang, and Mengji Lu
- Subjects
HEPATITIS B ,NATURAL immunity ,IMMUNE response ,CHRONIC hepatitis B ,HEPATITIS B virus - Abstract
Chronic hepatitis B virus (HBV) infection remains to be a substantial global burden, especially for end-stage liver diseases. It is well accepted that HBVspecific T and B cells are essential for controlling HBV infection. Toll-like receptors (TLRs) represent one of the major first-line antiviral defenses through intracellular signaling pathways that induce antiviral inflammatory cytokines and interferons, thereby shaping adaptive immunity. However, HBV has evolved strategies to counter TLR responses by suppressing the expression of TLRs and blocking the downstream signaling pathways, thus limiting HBVspecific adaptive immunity and facilitating viral persistence. Recent studies have stated that stimulation of the TLR signaling pathway by different TLR agonists strengthens host innate immune responses and results in suppression of HBV replication. In this review, we will discuss how TLR-mediated responses shape HBV-specific adaptive immunity as demonstrated in different experimental models. This information may provide important insight for HBV functional cure based on TLR agonists as immunomodulators. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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39. New-Generation Sequencing Technology in Diagnosis of Fungal Plant Pathogens: A Dream Comes True?
- Author
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Aragona, Maria, Haegi, Anita, Valente, Maria Teresa, Riccioni, Luca, Orzali, Laura, Vitale, Salvatore, Luongo, Laura, and Infantino, Alessandro
- Subjects
PHYTOPATHOGENIC microorganisms ,FUNGI classification ,PLANT diseases ,GENE targeting ,NUCLEOTIDE sequencing ,ARTIFICIAL intelligence - Abstract
The fast and continued progress of high-throughput sequencing (HTS) and the drastic reduction of its costs have boosted new and unpredictable developments in the field of plant pathology. The cost of whole-genome sequencing, which, until few years ago, was prohibitive for many projects, is now so affordable that a new branch, phylogenomics, is being developed. Fungal taxonomy is being deeply influenced by genome comparison, too. It is now easier to discover new genes as potential targets for an accurate diagnosis of new or emerging pathogens, notably those of quarantine concern. Similarly, with the development of metabarcoding and metagenomics techniques, it is now possible to unravel complex diseases or answer crucial questions, such as "What's in my soil?", to a good approximation, including fungi, bacteria, nematodes, etc. The new technologies allow to redraw the approach for disease control strategies considering the pathogens within their environment and deciphering the complex interactions between microorganisms and the cultivated crops. This kind of analysis usually generates big data that need sophisticated bioinformatic tools (machine learning, artificial intelligence) for their management. Herein, examples of the use of new technologies for research in fungal diversity and diagnosis of some fungal pathogens are reported. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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40. Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a randomized, double-blind, placebo-controlled trial.
- Author
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Pofi, Riccardo, Giannetta, Elisa, Feola, Tiziana, Galea, Nicola, Barbagallo, Federica, Campolo, Federica, Badagliacca, Roberto, Barbano, Biagio, Ciolina, Federica, Defeudis, Giuseppe, Filardi, Tiziana, Sesti, Franz, Minnetti, Marianna, Vizza, Carmine D., Pasqualetti, Patrizio, Caboni, Pierluigi, Carbone, Iacopo, Francone, Marco, Catalano, Carlo, and Pozzilli, Paolo
- Subjects
TADALAFIL ,HEART ,TYPE 2 diabetes ,PHOSPHODIESTERASE inhibitors ,DIABETIC cardiomyopathy ,RENAL artery - Abstract
Cyclic GMP–phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (−3.40°, −5.96; −0.84, P = 0.011) and fiber shortening (−1.19%, −2.24; −0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14
++ CD16− monocytes reduced, and Tie2+ monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications. Conditional cardioprotection: Phosphodiesterase 5 (PDE5) inhibition has been shown to have inconsistent cardioprotective effects. Here, Pofi et al. conducted a small phase 4 trial to assess sex differences in cardiac remodeling in patients with diabetes and diabetic cardiomyopathy treated with the PDE5 inhibitor tadalafil. They observed an improvement in cardiac shortening and torsion in men but not women, whereas circulating has-miR-199-5p was reduced and Klotho increased with treatment in both sexes. Certain populations of monocytes were also altered with treatment. Results highlight the importance of considering sex-specific differences in treatment response. [ABSTRACT FROM AUTHOR]- Published
- 2022
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41. Impact of weather parameters on Alternaria leaf spot of soybean incited by Alternaria alternata.
- Author
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Fagodiya, R. K., Trivedi, Amit, and Fagodia, B. L.
- Subjects
ALTERNARIA alternata ,LEAF spots ,ALTERNARIA ,SOWING ,SOYBEAN diseases & pests ,SOYBEAN sowing - Abstract
Weather attributes play a crucial role in the infection process and spread of pathogen. Alternaria leaf spot incited by Alternaria alternata is most destructive disease of soybean appeared in southern and eastern parts of Rajasthan as well as India. The effect of various weather parameters along with different date of sowing on the development of Alternaria leaf spot in susceptible soybean cultivar RKS-24 was investigated during Kharif season 2018 and 2019. The various weather factors viz., temperature, relative humidity and rainfall under inoculated conditions and with staggered dates of sowing were taken to observe effect on disease progression and their effect on seed yield. The maximum increase in disease severity (57.82 and 58.22%) and AUDPC (389.45 and 394.42) recorded in crop sown on 18th June (inoculated on 8th July). Lowest disease severity (39.80 and 38.50%) and AUDPC (266.18 and 259.18) were observed during 39–43th standard meteorological week (September, 24–October, 28) in year 2018 and 2019, respectively. Maximum seed yield (1699 kg ha
−1 ) was recorded in plants sown on 9th July, while, lowest seed yield was recorded in plants sown on 18th June with 1441.20 kg ha−1 . The trend of disease severity and AUDPC value decreased from early sowing to late sowing (18th June–9th July). Major reasons were fluctuations in temperature, rainfall and relative humidity. It was also observed that the soybean plants for Alternaria leaf spot disease in early sowing were predisposed and so farmers should be advised to practice delayed sowing of soybean crop. [ABSTRACT FROM AUTHOR]- Published
- 2022
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42. Prostate cancer and human papillomavirus infection: a recent literature review.
- Author
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Mahmoudi, Samira, Jafari-Sales, Abolfazl, Nasiri, Rozita, and Baghi, Hossein Bannazadeh
- Published
- 2022
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43. Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity.
- Author
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Duan, Tianhao, Du, Yang, Xing, Changsheng, Wang, Helen Y., and Wang, Rong-Fu
- Subjects
CELLULAR immunity ,TOLL-like receptors ,PATTERN perception receptors ,NATURAL immunity ,IMMUNE response - Abstract
Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host's defense against infectious diseases, autoimmune diseases, and cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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44. Searching, Structural Determination, and Diagnostic Performance Evaluation of Biomarker Molecules for Niemann-Pick Disease Type C Using Liquid Chromatography/Tandem Mass Spectrometry.
- Author
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Maekawa, Masamitsu and Mano, Nariyasu
- Published
- 2022
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45. T-lymphocytes Expression of Toll-like Receptors 2 and 4 in Acute Myeloid Leukemia Patients with Invasive Fungal Infections.
- Author
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Hammed, Muhamad R. Abdel, Elgendy, Sherein G., El-Mokhtar, Mohamed A., Sayed, Douaa, Mansour, Samar M., and Darwish, Abeer M.
- Subjects
ACUTE myeloid leukemia ,TOLL-like receptors ,MYCOSES ,BIOMARKERS ,T cells - Abstract
Background: Invasive fungal infections (IFIs) are important cause of mortality in acute myeloid leukemia (AML) patients on treatment with intensive induction chemotherapy. Toll-like receptors, mainly Toll-like receptors 2 and 4 (TLR2 and TLR4), play a considerable role in the host defense against microorganisms. The involvement of TLR signaling in modulation of innate immune response is extensively discussed, but the TLR expressions profiling on adaptive immune cells are not specified. Also, the expressions of TLRs and their association with the occurrence of IFIs in patients with AML are not studied. So, the novel aim of this study was to investigate the associations between the T-lymphocyte expression of TLR2 and TLR4 and the occurrence of IFIs in AML patients treated with intensive induction chemotherapy. Materials and Methods: One hundred twenty two newly diagnosed AML patients were evaluated. The laboratory diagnostic techniques for IFIs include culture, microscopic examination, histopathology, galactomannan assay and PCR. The expressions of TLR2 and TLR4 were analyzed by flow cytometry. The Control group included 20 age and sex-matched individuals. Results: There was a significant increase in the expression of TLR4 in AML patients with IFI compared to healthy controls (p = 0.001). TLR2 and TLR4 expressions increased significantly in AML patients with mixed fungal and bacterial infection compared to healthy controls (p= 0.002 and p=0.001, respectively). Conclusion: TLRs expressions could be important biological markers for the occurrence of IFI in non-M3 AML patients after intensive induction chemotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Controlul făinării frunzelor de gorun în culturi de pepinieră.
- Author
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Tăut, Ioan and Moldovan, Mircea
- Abstract
In the current context of environmental protection, a wide range of chemicals intended to control various pathogens in forest crops have been withdrawn due to the remnant of substances in the soil, thus polluting the natural environment. To achieve the proposed objective, experimental blocks were placed in the Sărata Nursery, Bistrița Forest District, and in the Rîtul de Jos Nursery, within the Livada Forest District, where sprays were made with fungicides with active substances - proquinazide 20% and azoxystrobin 200 g/l + difeconazole 125 g/l. Within the experimental blocks, three repetitions were established, in each repetition being materialized six treatment variants and an untreated control. In both experiments, after applying the treatments the degree of attack was distinctly significant between the treated variants (6.5-11.5%) and the untreated controls (18.2-31%). The effectiveness of the treatments has been moderate (47-69%), which requires new tests to evaluate the usefulness of these substances in the control of oak powdery mildew. [ABSTRACT FROM AUTHOR]
- Published
- 2022
47. Activation of Toll-like receptor 2 enhances peripheral and tumor-infiltrating CD8+ T cell cytotoxicity in patients with gastric cancer.
- Author
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Xu, Junli, Guo, Rongya, Jia, Jing, He, Yun, and He, Shuixiang
- Subjects
T cells ,TOLL-like receptors ,STOMACH cancer ,LACTATE dehydrogenase ,CANCER patients - Abstract
Background: Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8
+ T cells has not been fully elucidated in gastric cancer (GC). Materials and methods: Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8+ T cells was investigated. Purified CD8+ T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8+ T cells was measured. Direct and indirect contact coculture system between CD8+ T cells and AGS cells was set up. Modulation of TLR2 activation to CD8+ T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion. Results: TLR2 mRNA and TLR2+ cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8+ T cells. CD8+ T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8+ T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8+ T cells from GC, but not those from healthy individuals. Conclusion: The present data revealed an important immunomodulatory activity of TLR2 to CD8+ T cells in GC patients. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
48. Warming intensifies soil pathogen negative feedback on a temperate tree.
- Author
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Liu, Yu and He, Fangliang
- Subjects
PLANT diversity ,SOIL heating ,TREE mortality ,GLOBAL warming ,PLANT diseases ,PRUNUS - Abstract
Summary: The soil pathogen‐induced Janzen–Connell (JC) effect is considered as a primary mechanism regulating plant biodiversity worldwide. As predicted by the framework of the classic plant disease triangle, severity of plant diseases is often influenced by temperature, yet insufficient understanding of how increasing temperatures affect the JC effect contributes uncertainty in predictions about how global warming affects biodiversity.We conducted a 3‐yr field warming experiment, combining open‐top chambers with pesticide treatment, to test the effect of elevated temperatures on seedling mortality of a temperate tree species, Prunuspadus, from a genus with known susceptibility to soil‐borne pathogens.Elevated temperature significantly increased the mortality of P. padus seedlings in the immediate vicinity of parent trees, concurrent with increased relative abundance of pathogenic fungi identified to be virulent to Prunus species.Our study offers experimental evidence suggesting that global warming significantly intensifies the JC effect on a temperate tree species due to increased relative abundance of pathogenic fungi. This work advances our understanding about changes in the JC effect linked to ongoing global warming, which has important implications for predicting tree diversity in a warmer future. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
49. Variations in humus and fine root properties related to development stages in a temperate natural Beech forest.
- Author
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Azaryan, Mojtaba, Abrari Vajari, Kambiz, and Amanzadeh, Beitollah
- Subjects
BEECH ,FOREST management ,TEMPERATE forests ,HUMUS ,FOREST dynamics - Abstract
Understanding variations in soil humus and fine root properties in Oriental beech (Fagus orientalis L.) stand in response to development stages in temperate Hyrcanian forests is essential for sustainable forest management. The development stages of beech stand (initial, optimal and decay) were determined, and three plots of 100 × 100 m (1 ha) were chosen at each development stage. Five subplots in size 20 × 20 m were randomly selected at plots of 1 ha. The concentrations of humus elements (C, P, K, Mg, Fe and Zn) differed significantly among the development stages in spring and autumn seasons within Beech forest. The comparison of mean chemical compounds of humus layer in spring and autumn seasons using t test showed significant difference for each the development stage. Differences in C, N and P concentrations and also C/N and N/P ratios in fine roots of beech trees were significant among development stages, while C/P ratio was insignificant. The mean values of N and P for initial stage were higher, but C and N/P ratio were higher for optimal stage. The highest C/N value was observed in decay stage. There were statistically significant effects of development stages on fine root biomass and morphology traits at different diameter classes in beech trees. No statistically significant impacts of development stages were observed on fine root morphology of beech trees, except for fine root density. Our results reveal the important role that different development stages may play in Beech forest regarding variations in chemical properties of fine roots and soil humus. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
50. OryzaGenome2.1: Database of Diverse Genotypes in Wild Oryza Species.
- Author
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Kajiya-Kanegae, Hiromi, Ohyanagi, Hajime, Ebata, Toshinobu, Tanizawa, Yasuhiro, Onogi, Akio, Sawada, Yuji, Hirai, Masami Yokota, Wang, Zi-Xuan, Han, Bin, Toyoda, Atsushi, Fujiyama, Asao, Iwata, Hiroyoshi, Tsuda, Katsutoshi, Suzuki, Toshiya, Nosaka-Takahashi, Misuzu, Nonomura, Ken-ichi, Nakamura, Yasukazu, Kawamoto, Shoko, Kurata, Nori, and Sato, Yutaka
- Subjects
COMPARATIVE genomics ,ORYZA ,GENOTYPES ,GENOMICS ,SINGLE nucleotide polymorphisms ,SPECIES - Abstract
Background: OryzaGenome (http://viewer.shigen.info/oryzagenome21detail/index.xhtml), a feature within Oryzabase (https://shigen.nig.ac.jp/rice/oryzabase/), is a genomic database for wild Oryza species that provides comparative and evolutionary genomics approaches for the rice research community. Results: Here we release OryzaGenome2.1, the first major update of OryzaGenome. The main feature in this version is the inclusion of newly sequenced genotypes and their meta-information, giving a total of 217 accessions of 19 wild Oryza species (O. rufipogon, O. barthii, O. longistaminata, O. meridionalis, O. glumaepatula, O. punctata, O. minuta, O. officinalis, O. rhizomatis, O. eichingeri, O. latifolia, O. alta, O. grandiglumis, O. australiensis, O. brachyantha, O. granulata, O. meyeriana, O. ridleyi, and O. longiglumis). These 19 wild species belong to 9 genome types (AA, BB, CC, BBCC, CCDD, EE, FF, GG, and HHJJ), representing wide genomic diversity in the genus. Using the genotype information, we analyzed the genome diversity of Oryza species. Other features of OryzaGenome facilitate the use of information on single nucleotide polymorphisms (SNPs) between O. sativa and its wild progenitor O. rufipogon in rice research, including breeding as well as basic science. For example, we provide Variant Call Format (VCF) files for genome-wide SNPs of 33 O. rufipogon accessions against the O. sativa reference genome, IRGSP1.0. In addition, we provide a new SNP Effect Table function, allowing users to identify SNPs or small insertion/deletion polymorphisms in the 33 O. rufipogon accessions and to search for the effect of these polymorphisms on protein function if they reside in the coding region (e.g., are missense or nonsense mutations). Furthermore, the SNP Viewer for 446 O. rufipogon accessions was updated by implementing new tracks for possible selective sweep regions and highly mutated regions that were potentially exposed to selective pressures during the process of domestication. Conclusion: OryzaGenome2.1 focuses on comparative genomic analysis of diverse wild Oryza accessions collected around the world and on the development of resources to speed up the identification of critical trait-related genes, especially from O. rufipogon. It aims to promote the use of genotype information from wild accessions in rice breeding and potential future crop improvements. Diverse genotypes will be a key resource for evolutionary studies in Oryza, including polyploid biology. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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