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排序方式: 共有502条查询结果,搜索用时 12 毫秒
141.
Kugathasan S Baldassano RN Bradfield JP Sleiman PM Imielinski M Guthery SL Cucchiara S Kim CE Frackelton EC Annaiah K Glessner JT Santa E Willson T Eckert AW Bonkowski E Shaner JL Smith RM Otieno FG Peterson N Abrams DJ Chiavacci RM Grundmeier R Mamula P Tomer G Piccoli DA Monos DS Annese V Denson LA Grant SF Hakonarson H 《Nature genetics》2008,40(10):1211-1215
Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively. 相似文献
142.
Brown KM Macgregor S Montgomery GW Craig DW Zhao ZZ Iyadurai K Henders AK Homer N Campbell MJ Stark M Thomas S Schmid H Holland EA Gillanders EM Duffy DL Maskiell JA Jetann J Ferguson M Stephan DA Cust AE Whiteman D Green A Olsson H Puig S Ghiorzo P Hansson J Demenais F Goldstein AM Gruis NA Elder DE Bishop JN Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Martin NG Trent JM Mann GJ Hayward NK 《Nature genetics》2008,40(7):838-840
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. 相似文献
143.
Willer CJ Sanna S Jackson AU Scuteri A Bonnycastle LL Clarke R Heath SC Timpson NJ Najjar SS Stringham HM Strait J Duren WL Maschio A Busonero F Mulas A Albai G Swift AJ Morken MA Narisu N Bennett D Parish S Shen H Galan P Meneton P Hercberg S Zelenika D Chen WM Li Y Scott LJ Scheet PA Sundvall J Watanabe RM Nagaraja R Ebrahim S Lawlor DA Ben-Shlomo Y Davey-Smith G Shuldiner AR Collins R Bergman RN Uda M Tuomilehto J Cao A Collins FS Lakatta E Lathrop GM Boehnke M Schlessinger D Mohlke KL 《Nature genetics》2008,40(2):161-169
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. 相似文献
144.
145.
Insect communication: 'no entry' signal in ant foraging 总被引:1,自引:0,他引:1
Forager ants lay attractive trail pheromones to guide nestmates to food, but the effectiveness of foraging networks might be improved if pheromones could also be used to repel foragers from unrewarding routes. Here we present empirical evidence for such a negative trail pheromone, deployed by Pharaoh's ants (Monomorium pharaonis) as a 'no entry' signal to mark an unrewarding foraging path. This finding constitutes another example of the sophisticated control mechanisms used in self-organized ant colonies. 相似文献
146.
Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN 总被引:1,自引:0,他引:1
Dacey DM Liao HW Peterson BB Robinson FR Smith VC Pokorny J Yau KW Gamlin PD 《Nature》2005,433(7027):749-754
Human vision starts with the activation of rod photoreceptors in dim light and short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway, arising from a population of retinal ganglion cells, was discovered in nocturnal rodents. These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction. Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and (L + M) cone-derived light responses combine in these giant cells to signal irradiance over the full dynamic range of human vision. In accordance with cone-based colour opponency, the giant cells project to the lateral geniculate nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception. 相似文献
147.
Carulla N Caddy GL Hall DR Zurdo J Gairí M Feliz M Giralt E Robinson CV Dobson CM 《Nature》2005,436(7050):554-558
Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of beta-sheets oriented parallel to the fibril axis. Such structures were first recognized in clinical disorders, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease. 相似文献
148.
The deep ocean is home to a group of broad-collared hemichordates--the so-called 'lophenteropneusts'--that have been photographed gliding on the sea floor but have not previously been collected. It has been claimed that these worms have collar tentacles and blend morphological features of the two main hemichordate body plans, namely the tentacle-less enteropneusts and the tentacle-bearing pterobranchs. Consequently, lophenteropneusts have been invoked as missing links to suggest that the former evolved into the latter. The most significant aspect of the lophenteropneust hypothesis is its prediction that the fundamental body plan within a basal phylum of deuterostomes was enteropneust-like. The assumption of such an ancestral state influences ideas about the evolution of the vertebrates from the invertebrates. Here we report on the first collected specimen of a broad-collared, deep-sea enteropneust and describe it as a new family, genus and species. The collar, although disproportionately broad, lacks tentacles. In addition, we find no evidence of tentacles in the available deep-sea photographs (published and unpublished) of broad-collared enteropneusts, including those formerly designated as lophenteropneusts. Thus, the lophenteropneust hypothesis was based on misinterpretation of deep-sea photographs of low quality and should no longer be used to support the idea that the enteropneust body plan is basal within the phylum Hemichordata. 相似文献
149.
Yen AS Gellert R Schröder C Morris RV Bell JF Knudson AT Clark BC Ming DW Crisp JA Arvidson RE Blaney D Brückner J Christensen PR DesMarais DJ de Souza PA Economou TE Ghosh A Hahn BC Herkenhoff KE Haskin LA Hurowitz JA Joliff BL Johnson JR Klingelhöfer G Madsen MB McLennan SM McSween HY Richter L Rieder R Rodionov D Soderblom L Squyres SW Tosca NJ Wang A Wyatt M Zipfel J 《Nature》2005,436(7047):49-54
The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material. 相似文献
150.
Haskin LA Wang A Jolliff BL McSween HY Clark BC Des Marais DJ McLennan SM Tosca NJ Hurowitz JA Farmer JD Yen A Squyres SW Arvidson RE Klingelhöfer G Schröder C de Souza PA Ming DW Gellert R Zipfel J Brückner J Bell JF Herkenhoff K Christensen PR Ruff S Blaney D Gorevan S Cabrol NA Crumpler L Grant J Soderblom L 《Nature》2005,436(7047):66-69
Gusev crater was selected as the landing site for the Spirit rover because of the possibility that it once held a lake. Thus one of the rover's tasks was to search for evidence of lake sediments. However, the plains at the landing site were found to be covered by a regolith composed of olivine-rich basaltic rock and windblown 'global' dust. The analyses of three rock interiors exposed by the rock abrasion tool showed that they are similar to one another, consistent with having originated from a common lava flow. Here we report the investigation of soils, rock coatings and rock interiors by the Spirit rover from sol (martian day) 1 to sol 156, from its landing site to the base of the Columbia hills. The physical and chemical characteristics of the materials analysed provide evidence for limited but unequivocal interaction between water and the volcanic rocks of the Gusev plains. This evidence includes the softness of rock interiors that contain anomalously high concentrations of sulphur, chlorine and bromine relative to terrestrial basalts and martian meteorites; sulphur, chlorine and ferric iron enrichments in multilayer coatings on the light-toned rock Mazatzal; high bromine concentration in filled vugs and veins within the plains basalts; positive correlations between magnesium, sulphur and other salt components in trench soils; and decoupling of sulphur, chlorine and bromine concentrations in trench soils compared to Gusev surface soils, indicating chemical mobility and separation. 相似文献