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排序方式: 共有168条查询结果,搜索用时 296 毫秒
1.
Kaneko H Dridi S Tarallo V Gelfand BD Fowler BJ Cho WG Kleinman ME Ponicsan SL Hauswirth WW Chiodo VA Karikó K Yoo JW Lee DK Hadziahmetovic M Song Y Misra S Chaudhuri G Buaas FW Braun RE Hinton DR Zhang Q Grossniklaus HE Provis JM Madigan MC Milam AH Justice NL Albuquerque RJ Blandford AD Bogdanovich S Hirano Y Witta J Fuchs E Littman DR Ambati BK Rudin CM Chong MM Provost P Kugel JF Goodrich JA Dunaief JL Baffi JZ Ambati J 《Nature》2011,471(7338):325-330
2.
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
3.
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
4.
We assessed the influence of water depth, extent of unobstructed view, and human disturbance features on use of roost sites by Sandhill Cranes along the Platte River, Nebraska, during spring migratory stopover. Aerial photos taken near dawn were used to determine areas of flock use and habitat availability in four sample reaches, and measurements were made on the ground at flock roost areas. In general, depths of 1-13 cm were used by sandhill cranes in greater proportion than those available. Exposed sandbars and depths >20 cm were avoided, while depths of 14-19 cm were used in proportion to their availability. Sites 11-50 m from the nearest visual obstruction were used significantly greater than their availability, while sites 0-4 and >50 m from visual obstructions were avoided. Sandhill Cranes avoided sites near paved roads, gravel roads, single dwellings, and bridges when selecting roost sites; however, they did not appear to be disturbed by private roads, groups of residential buildings, gravel pits, railroads, or electrical transmission lines. 相似文献
5.
6.
Engineering a mouse balancer chromosome. 总被引:15,自引:0,他引:15
B Zheng M Sage W W Cai D M Thompson B C Tavsanli Y C Cheah A Bradley 《Nature genetics》1999,22(4):375-378
Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs. 相似文献
7.
Repeated denervation and reinnervation of skeletal muscle 总被引:1,自引:0,他引:1
8.
Hepatitis B and serum DNA polymerase activities in chimpanzees 总被引:4,自引:0,他引:4
9.
10.
The knockout mouse project 总被引:1,自引:0,他引:1
Austin CP Battey JF Bradley A Bucan M Capecchi M Collins FS Dove WF Duyk G Dymecki S Eppig JT Grieder FB Heintz N Hicks G Insel TR Joyner A Koller BH Lloyd KC Magnuson T Moore MW Nagy A Pollock JD Roses AD Sands AT Seed B Skarnes WC Snoddy J Soriano P Stewart DJ Stewart F Stillman B Varmus H Varticovski L Verma IM Vogt TF von Melchner H Witkowski J Woychik RP Wurst W Yancopoulos GD Young SG Zambrowicz B 《Nature genetics》2004,36(9):921-924
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. 相似文献