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51.
Nalls MA Couper DJ Tanaka T van Rooij FJ Chen MH Smith AV Toniolo D Zakai NA Yang Q Greinacher A Wood AR Garcia M Gasparini P Liu Y Lumley T Folsom AR Reiner AP Gieger C Lagou V Felix JF Völzke H Gouskova NA Biffi A Döring A Völker U Chong S Wiggins KL Rendon A Dehghan A Moore M Taylor K Wilson JG Lettre G Hofman A Bis JC Pirastu N Fox CS Meisinger C Sambrook J Arepalli S Nauck M Prokisch H Stephens J Glazer NL Cupples LA Okada Y Takahashi A Kamatani Y Matsuda K Tsunoda T Tanaka T Kubo M 《PLoS genetics》2011,7(6):e1002113
White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds. 相似文献
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Isoform-specific null mutations were used to define the functions of three orphan members of the nuclear receptor superfamily, E75A, E75B, and E75C, encoded by the E75 early ecdysteroid-inducible gene. E75B mutants are viable and fertile, while E75C mutants die as adults. In contrast, E75A mutants have a reduced ecdysteroid titer during larval development, resulting in developmental delays, developmental arrests, and molting defects. Remarkably, some E75A mutant second instar larvae display a heterochronic phenotype in which they induce genes specific to the third instar and pupariate without undergoing a molt. We propose that ecdysteroid-induced E75A expression defines a feed-forward pathway that amplifies or maintains the ecdysteroid titer during larval development, ensuring proper temporal progression through the life cycle. 相似文献
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Etienne Morel Sara Ghezzal Géraldine Lucchi Caroline Truntzer Jean-Paul Pais de Barros Françoise Simon-Plas Sylvie Demignot Chieko Mineo Philip W. Shaul Armelle Leturque Monique Rousset Véronique Carrière 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(2):199-211
Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. 相似文献
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Luciferase-dependent assays, important for biochemical analyses of cytotoxicity and reporter genes, may be perturbed by compounds interfering with the luciferase reaction. We analyzed the impact of different aluminum (Al) species on a luciferase-based assay for determination of cellular adenosine triphosphate. Al0 nanoparticles (Al0–NPs) but not Al2O3–NPs decreased luminescence, correlated to high absorbance of Al0–NPs. By contrast, Al ions increased the luminescent signal. Data demonstrate that luciferase-dependent assays can be reciprocally disturbed by Al–NPs or Al ions in a specific manner, depending on the particular Al species. Careful interpretation of data from such experiments is essential in order to obtain conclusive results. 相似文献
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Plant species may remain morphologically distinct despite gene exchange with congeners, yet little is known about the genomewide pattern of introgression among species. Here we analyze the effects of persistent gene flow on genomic differentiation between the sympatric sunflower species Helianthus annuus and H. petiolaris. While the species are strongly isolated in testcrosses, genetic distances at 108 microsatellite loci and 14 sequenced genes are highly variable and much lower (on average) than for more closely related but historically allopatric congeners. Our analyses failed to detect a positive association between levels of genetic differentiation and chromosomal rearrangements (as reported in a prior publication) or proximity to QTL for morphological differences or hybrid sterility. However, a significant increase in differentiation was observed for markers within 5 cM of chromosomal breakpoints. Together, these results suggest that islands of differentiation between these two species are small, except in areas of low recombination. Furthermore, only microsatellites associated with ESTs were identified as outlier loci in tests for selection, which might indicate that the ESTs themselves are the targets of selection rather than linked genes (or that coding regions are not randomly distributed). In general, these results indicate that even strong and genetically complex reproductive barriers cannot prevent widespread introgression. 相似文献
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Developing core outcome set for vitiligo clinical trials: international e‐Delphi consensus 下载免费PDF全文
Viktoria Eleftheriadou Kim Thomas Nanja van Geel Iltefat Hamzavi Henry Lim Tamio Suzuki Ichiro Katayama Tag Anbar Marwa Abdallah Laïla Benzekri Yvon Gauthier John Harris Caio Cesar Silva de Castro Amit Pandya Boon Kee Goh Cheng‐Che E. Lan Naoki Oiso Ahmed Al Issa Samia Esmat Caroline Le Poole Ai‐Young Lee Davinder Parsad Alain Taieb Mauro Picardo Khaled Ezzedine 《Pigment cell & melanoma research》2015,28(3):363-369
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Damien Formey Erika Sallet Christine Lelandais-Brière Cécile Ben Pilar Bustos-Sanmamed Andreas Niebel Florian Frugier Jean Philippe Combier Frédéric Debellé Caroline Hartmann Julie Poulain Frédérick Gavory Patrick Wincker Christophe Roux Laurent Gentzbittel Jér?me Gouzy Martin Crespi 《Genome biology》2014,15(9)