排序方式: 共有37条查询结果,搜索用时 156 毫秒
21.
Depaepe V Suarez-Gonzalez N Dufour A Passante L Gorski JA Jones KR Ledent C Vanderhaeghen P 《Nature》2005,435(7046):1244-1250
Mechanisms controlling brain size include the regulation of neural progenitor cell proliferation, differentiation, survival and migration. Here we show that ephrin-A/EphA receptor signalling plays a key role in controlling the size of the mouse cerebral cortex by regulating cortical progenitor cell apoptosis. In vivo gain of EphA receptor function, achieved through ectopic expression of ephrin-A5 in early cortical progenitors expressing EphA7, caused a transient wave of neural progenitor cell apoptosis, resulting in premature depletion of progenitors and a subsequent dramatic decrease in cortical size. In vitro treatment with soluble ephrin-A ligands similarly induced the rapid death of cultured dissociated cortical progenitors in a caspase-3-dependent manner, thereby confirming a direct effect of ephrin/Eph signalling on apoptotic cascades. Conversely, in vivo loss of EphA function, achieved through EphA7 gene disruption, caused a reduction in apoptosis occurring normally in forebrain neural progenitors, resulting in an increase in cortical size and, in extreme cases, exencephalic forebrain overgrowth. Together, these results identify ephrin/Eph signalling as a physiological trigger for apoptosis that can alter brain size and shape by regulating the number of neural progenitors. 相似文献
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23.
Gut hormone PYY(3-36) physiologically inhibits food intake 总被引:42,自引:0,他引:42
Batterham RL Cowley MA Small CJ Herzog H Cohen MA Dakin CL Wren AM Brynes AE Low MJ Ghatei MA Cone RD Bloom SR 《Nature》2002,418(6898):650-654
Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway. 相似文献
24.
Benzinou M Creemers JW Choquet H Lobbens S Dina C Durand E Guerardel A Boutin P Jouret B Heude B Balkau B Tichet J Marre M Potoczna N Horber F Le Stunff C Czernichow S Sandbaek A Lauritzen T Borch-Johnsen K Andersen G Kiess W Körner A Kovacs P Jacobson P Carlsson LM Walley AJ Jørgensen T Hansen T Pedersen O Meyre D Froguel P 《Nature genetics》2008,40(8):943-945
Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity. 相似文献
25.
Audrey Gabel Callie Ackerman Mark Gabel Elizabeth Krueger Scott Weins Linda Zierer 《西北部美国博物学家》2011,70(1)
During the summers of 2005 and 2006, northern flying squirrels ( Glaucomys sabrinus Shaw) were live-captured in the northern Black Hills of South Dakota from mixed deciduous/coniferous and coniferous habitats. Squirrel captures were significantly correlated with volume of downed wood and number of snags. Diets were examined from scat collections ( n = 40, deciduous/coniferous; n = 10, coniferous). Number of fungal spores in the scat was significantly correlated with number of snags. From each scat collection, the frequencies of plant, animal, fungal, and unidentified components were determined. Hypogeous fungi were a frequent component of the diet, being found in 98.3% and 78.8% of the scat observed in 2005 and 2006. In 2006, as the frequency of dietary fungi decreased, the frequency of plant material increased from <1.0% to 8.0% and frequency of unidentified material increased from 2.0% to 74.0%. Animal content in the scat was negligible (<1.0% to 1.0%). Rhizopogon was the most frequently occurring hypogeous fungus observed. Rhizopogon spores made up 97.9% of the spores counted in 2005 and 96.4% in 2006. Elaphomyces, Gautieria, Geopora, Hymenogaster, and Hysterangium were observed at much lower frequencies. Sporocarps were collected throughout the trapping periods. Fourteen were collected in 2005 and 12 in 2006. Of the 26 sporocarps collected, 11 were Rhizopogon, 4 Elaphomyces, 2 Gautieria, 1 Hymenogaster, 7 Hysterangium, and 1 Tuber. This study is the first to examine flying squirrel diets in the Black Hills and the first to report Elaphomyces, Gautieria, Hymenogaster, Hysterangium, Rhizopogon, and Tuber sporocarps from the South Dakota Black Hills. 相似文献
26.
Megan Chircop Chandra S. Malladi Audrey T. Lian Scott L. Page Michael Zavortink Christopher P. Gordon Adam McCluskey Phillip J. Robinson 《Cellular and molecular life sciences : CMLS》2010,67(21):3725-3737
Successful completion of cytokinesis requires the spatio-temporal regulation of protein phosphorylation and the coordinated
activity of protein kinases and phosphatases. Many mitotic protein kinases are well characterized while mitotic phosphatases
are largely unknown. Here, we show that the Ca2+- and calmodulin-dependent phosphatase, calcineurin (CaN), is required for cytokinesis in mammalian cells, functioning specifically
at the abscission stage. CaN inhibitors induce multinucleation in HeLa cells and prolong the time cells spend connected via
an extended intracellular bridge. Upon Ca2+ influx during cytokinesis, CaN is activated, targeting a set of proteins for dephosphorylation, including dynamin II (dynII).
At the intracellular bridge, phospho-dynII and CaN are co-localized to dual flanking midbody rings (FMRs) that reside on either
side of the central midbody ring. CaN activity and disassembly of the FMRs coincide with abscission. Thus, CaN activity at
the midbody plays a key role in regulating the completion of cytokinesis in mammalian cells. 相似文献
27.
Caenorhabditis elegans homologues of the retinoblastoma (Rb) tumour suppressor complex specify cell lineage during development. Here we show that mutations in Rb pathway components enhance RNA interference (RNAi) and cause somatic cells to express genes and elaborate perinuclear structures normally limited to germline-specific P granules. Furthermore, particular gene inactivations that disrupt RNAi reverse the cell lineage transformations of Rb pathway mutants. These findings suggest that mutations in Rb pathway components cause cells to revert to patterns of gene expression normally restricted to germ cells. Rb may act by a similar mechanism to transform mammalian cells. 相似文献
28.
GoDARTS UKPDS Diabetes Pharmacogenetics Study Group;Wellcome Trust Case Control Consortium Zhou K Bellenguez C Spencer CC Bennett AJ Coleman RL Tavendale R Hawley SA Donnelly LA Schofield C Groves CJ Burch L Carr F Strange A Freeman C Blackwell JM Bramon E Brown MA Casas JP Corvin A Craddock N Deloukas P Dronov S Duncanson A Edkins S Gray E Hunt S Jankowski J Langford C Markus HS Mathew CG Plomin R Rautanen A Sawcer SJ Samani NJ Trembath R Viswanathan AC Wood NW;MAGIC investigators 《Nature genetics》2011,43(2):117-120
Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. 相似文献
29.
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium Strange A Capon F Spencer CC Knight J Weale ME Allen MH Barton A Band G Bellenguez C Bergboer JG Blackwell JM Bramon E Bumpstead SJ Casas JP Cork MJ Corvin A Deloukas P Dilthey A Duncanson A Edkins S Estivill X Fitzgerald O Freeman C Giardina E Gray E Hofer A Hüffmeier U Hunt SE Irvine AD Jankowski J Kirby B Langford C Lascorz J Leman J Leslie S Mallbris L Markus HS Mathew CG McLean WH McManus R 《Nature genetics》2010,42(11):985-990
To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis. 相似文献
30.
Eeles RA Kote-Jarai Z Giles GG Olama AA Guy M Jugurnauth SK Mulholland S Leongamornlert DA Edwards SM Morrison J Field HI Southey MC Severi G Donovan JL Hamdy FC Dearnaley DP Muir KR Smith C Bagnato M Ardern-Jones AT Hall AL O'Brien LT Gehr-Swain BN Wilkinson RA Cox A Lewis S Brown PM Jhavar SG Tymrakiewicz M Lophatananon A Bryant SL;UK Genetic Prostate Cancer Study Collaborators;British Association of Urological Surgeons' Section of Oncology;UK ProtecT Study Collaborators Horwich A Huddart RA 《Nature genetics》2008,40(3):316-321
Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at =60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 ng/ml). We analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. We identified seven loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 x 10(-8) to P = 8.7 x 10(-29)). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3. 相似文献