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排序方式: 共有495条查询结果,搜索用时 968 毫秒
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Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
23.
Liu F Thirumangalathu S Gallant NM Yang SH Stoick-Cooper CL Reddy ST Andl T Taketo MM Dlugosz AA Moon RT Barlow LA Millar SE 《Nature genetics》2007,39(1):106-112
Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning. 相似文献
24.
Steven J. Collins Carolin Tumpach Bradley R. Groveman Simon C. Drew Cathryn L. Haigh 《Cellular and molecular life sciences : CMLS》2018,75(17):3231-3249
Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life. 相似文献
25.
Kristin M. Thompson Matthew J. Holloran Steven J. Slater Jarren L. Kuipers Stanley H. Anderson 《西北部美国博物学家》2011,66(3)
Populations of Greater Sage-Grouse ( Centrocercus urophasianus ) have been declining throughout their range since the 1960s. Productivity, which includes production and survival of young, is often cited as a factor in these declines. We monitored radio-equipped Greater Sage-Grouse at 3 sites in western Wyoming to assess early brood-rearing habitat use (through 14 days post-hatch) and productivity. Logistic and linear regression analyses with Akaike's Information Criterion were used to evaluate early brooding habitat use and to examine relationships between productivity and vegetation, insect size and abundance, and weather parameters. Females with broods were found in areas with greater sagebrush canopy and grass cover, and fewer invertebrates compared to random areas. The number of juveniles per female (estimated from wing barrel collections during fall harvest) was positively related to the abundance of medium-length Hymenoptera and grass cover, and the proportion of females with confirmed chicks 14 days post-hatch was positively related to abundance of medium-length Coleoptera and total herbaceous cover. Although the specific parameters varied slightly, Greater Sage-Grouse productivity in Wyoming appeared to be associated with a combination of insect and herbaceous cover elements. Managing for abundant and diverse insect communities within dense protective sagebrush stands should help ensure high-quality early brood-rearing habitat and increased Greater Sage-Grouse productivity. 相似文献
26.
Matmati M Jacques P Maelfait J Verheugen E Kool M Sze M Geboes L Louagie E Mc Guire C Vereecke L Chu Y Boon L Staelens S Matthys P Lambrecht BN Schmidt-Supprian M Pasparakis M Elewaut D Beyaert R van Loo G 《Nature genetics》2011,43(9):908-912
A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies. 相似文献
27.
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease 总被引:1,自引:0,他引:1
Naj AC Jun G Beecham GW Wang LS Vardarajan BN Buros J Gallins PJ Buxbaum JD Jarvik GP Crane PK Larson EB Bird TD Boeve BF Graff-Radford NR De Jager PL Evans D Schneider JA Carrasquillo MM Ertekin-Taner N Younkin SG Cruchaga C Kauwe JS Nowotny P Kramer P Hardy J Huentelman MJ Myers AJ Barmada MM Demirci FY Baldwin CT Green RC Rogaeva E St George-Hyslop P Arnold SE Barber R Beach T Bigio EH Bowen JD Boxer A Burke JR Cairns NJ Carlson CS Carney RM Carroll SL Chui HC Clark DG Corneveaux J Cotman CW 《Nature genetics》2011,43(5):436-441
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility. 相似文献
28.
McCarroll SA Hadnott TN Perry GH Sabeti PC Zody MC Barrett JC Dallaire S Gabriel SB Lee C Daly MJ Altshuler DM;International HapMap Consortium 《Nature genetics》2006,38(1):86-92
The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies. 相似文献
29.
30.
For analysts there is a tradeoff between the accuracy and the timeliness of their forecasts. Prior literature heavily investigates analyst forecast accuracy. Few papers investigate the importance of timeliness. To our best knowledge, there are no empirical papers to date to investigate the dynamic interplay between these key characteristics. We show that if analysts experience a period of high accuracy relative to their peers, they subsequently focus more on the timeliness of their forecasts in the subsequent period and thus issue their forecasts earlier than they did in the prior period. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献