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41.
Gaudet MM Kirchhoff T Green T Vijai J Korn JM Guiducci C Segrè AV McGee K McGuffog L Kartsonaki C Morrison J Healey S Sinilnikova OM Stoppa-Lyonnet D Mazoyer S Gauthier-Villars M Sobol H Longy M Frenay M GEMO Study Collaborators Hogervorst FB Rookus MA Collée JM Hoogerbrugge N van Roozendaal KE;HEBON Study Collaborators Piedmonte M Rubinstein W Nerenstone S Van Le L Blank SV Caldés T de la Hoya M Nevanlinna H Aittomäki K Lazaro C Blanco I Arason A Johannsson OT Barkardottir RB Devilee P 《PLoS genetics》2010,6(10):e1001183
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. 相似文献
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Marijn Rutgers Daniël BF Saris Wouter JA Dhert Laura B Creemers 《Arthritis research & therapy》2010,12(3):R114
Introduction
Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fluid (SF) cytokine levels following intraarticular ACS administration. 相似文献43.
Ceramide regulates many cellular processes, including cell growth, differentiation, and apoptosis. Although the effects of exogenous bacterial neutral sphingomyelinase (SMase) in Xenopus laevis oocytes have been investigated, its microinjection into oocytes has not been reported previously. Thus, we compared the incubation versus microinjection of the neutral Bacillus cereus sphingomyelinase (bSMase) to examine whether the topology of ceramide generation determines its effects on the fate of oocytes. In agreement with previous findings, incubation of mature stage VI oocytes with bSMase increased ceramide levels in oocyte extracts over time, causing the germinal vesicle breakdown indicative of maturation, without evidence of cytotoxicity. In contrast, bSMase microinjection, which increased ceramide levels in a time- and dose-dependent manner, resulted in oocyte apoptosis characterized by reactive oxygen species (ROS) generation, reduced glutathione (GSH) depletion in cytosol and mitochondria, release of cytochrome c and Smac/Diablo from mitochondria, and caspase-3 activation. Microinjection of acidic SMase from human placenta recapitulated the apoptotic effects of bSMase microinjection. Preincubation of oocytes with GSH-ethyl ester before bSMase microinjection prevented ROS generation and mitochondrial downstream events, thus protecting oocytes from bSMase-induced death. These findings show a divergent action of bSMase-induced ceramide on oocyte maturation or apoptosis depending on the intracellular site where ceramide is generated. 相似文献
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Sbragaglia Valerio Espasandín Lucía Coco Salvatore Felici Alberto Correia Ricardo A. Coll Marta Arlinghaus Robert 《Reviews in Fish Biology and Fisheries》2022,32(2):687-700
Reviews in Fish Biology and Fisheries - Fisheries are among the human activities that are most strongly affected by ongoing climate-related changes in the presence and abundance of fish species... 相似文献
47.
Morphological parameters of abundant and threatened chondrichthyans of the northwestern Mediterranean Sea
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C. Barría J. Navarro M. Coll U. Fernandez‐Arcaya R. Sáez‐Liante 《Zeitschrift fur angewandte Ichthyologie》2015,31(1):114-119
The diversity of chondrichthyans in the Mediterranean Sea is relatively high; however, available data indicate that this group is declining in abundance and several species are becoming rare. As a result, the collection of biological data is a priority for demographic models, stock assessments, and food web analysis. In the present study, we report morphological parameters and length–weight relationships of several chondrichthyan species, both abundant and threatened, from the western Mediterranean Sea. Samples were obtained with commercial and scientific bottom trawl vessels between 2001 and 2013. A total of 893 individuals belonging to 11 families and 20 species were weighed and total lengths measured. In addition, seven species of large demersal sharks were measured and length–length relationships obtained to study the relationships between different body length measurements. All species showed positive allometric or isometric growth, except for Centroscymnus coelolepis. The results of the length–weight relationships reveal differences between the western Mediterranean and nearby areas, depending on the species studied. 相似文献
48.
R Gon?alves LA Szmuchrowski LS Prado BP Couto JCQ Machado VO Damasceno JA Lamounier 《Biology of sport / Institute of Sport》2015,32(3):255-260
The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children. 相似文献
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David Gendron Anne-Marie Lemay Claudine Tremblay Laetitia JA Lai Anick Langlois émilie Bernatchez Nicolas Flamand Marie-Renée Blanchet Anthony S Don Ynuk Bossé élyse Bissonnette David Marsolais 《Respiratory research》2015,16(1)