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排序方式: 共有405条查询结果,搜索用时 421 毫秒
221.
Sawaya MR Sambashivan S Nelson R Ivanova MI Sievers SA Apostol MI Thompson MJ Balbirnie M Wiltzius JJ McFarlane HT Madsen AØ Riekel C Eisenberg D 《Nature》2007,447(7143):453-457
Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-beta spine. The atomic architecture of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein Sup35, was recently revealed by X-ray microcrystallography. It is a pair of beta-sheets, with the facing side chains of the two sheets interdigitated in a dry 'steric zipper'. Here we report some 30 other segments from fibril-forming proteins that form amyloid-like fibrils, microcrystals, or usually both. These include segments from the Alzheimer's amyloid-beta and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, alpha-synuclein and beta(2)-microglobulin, suggesting that common structural features are shared by amyloid diseases at the molecular level. Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains. 相似文献
222.
223.
Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive 总被引:1,自引:0,他引:1
Guccione E Bassi C Casadio F Martinato F Cesaroni M Schuchlautz H Lüscher B Amati B 《Nature》2007,449(7164):933-937
224.
Christian L. Cox Alison R. Davis Rabosky Iris A. Holmes Jacobo Reyes-Velasco Corey E. Roelke Eric N. Smith 《Journal of Natural History》2018,52(13-16):945-988
ABSTRACTDelimiting species is a crucial goal of integrative biology, and yet can be misled by homoplasy and high levels of morphological variation. The snake tribe Sonorini contains three genera that have long confounded taxonomists: Chilomeniscus, Chionactis and Sonora. Dynamic colour evolution in this group, including rampant geographic variation in colour and colour polymorphism, has led to a chaotic taxonomy. We used mitochondrial and high-throughput nuclear data (ddRADseq) and complete taxonomic sampling of each genus to reconstruct phylogenetic relationships and systematically revise the genus. Our research revealed that Sonora is paraphyletic with regards to Chilomeniscus and Chionactis and that at least one species (S. semiannulata) is paraphyletic with respect to at least one other recognized species. Additionally, we found substantial undescribed genetic diversity within multiple species which is incongruent with morphological variation in coloration. Accordingly, we proposed synonymizing Chionactis and Chilomeniscus with Sonora, which has taxonomic priority over both genera. As we found genetic evidence that supported some of the historically delimited diversity within multiple taxa, we revised species-level taxonomy accordingly. This new taxonomy recognizes a revised genus of Sonora that contains 15 species of diminutive and often brightly coloured snakes that are distributed from central Mexico to north-western USA.http://www.zoobank.org/urn:lsid:zoobank.org:pub:45A553D8-6435-4E0A-84ED-DF31E2CCD872 相似文献
225.
1 Results Detection of biomolecules relies on a highly specific recognition event between an analyte biomolecule and a probe that is often closely connected or integrated within a sensor transducer element to provide a suitable signal. More widespread application of gene detection on a routine basis demands the development of a new generation of gene sensors that are fast, reliable and cost-effective.Conjugated polymers (CPs) have been shown to be a versatile substrate for DNA sensor construction, where... 相似文献
226.
目的:探讨磷脂酰肌醇3激酶/丝氨酸苏氨酸蛋白激酶B(PI3K/AKT)信号通路特异性抑制剂LY294002在JurkatT细胞增殖中的作用.方法:以急性T细胞白血病胞(Jurkat T 细胞)为模型,PD98059和阿霉素为阳性对照,在倒置显微镜下观察LY294002对Jurkat T细胞的集落形成的影响,四甲基偶氮唑蓝(MTT)检测LY294002处理后Jurkat T细胞的增殖,流式细胞术检测LY294002处理后Jurkat T细胞周期的变化,Western blotting方法检测Jurkat T细胞中ICBP90蛋白的表达以确定其与LY294002抑制Jurkat T细胞增殖的关系.结果:LY294002能够显著抑制Jurkat T细胞的集落形成和增殖,使Jurkat T细胞停滞于G2/M 期,导致Jurkat T细胞ICBP90蛋白的表达显著降低,LY294002与阿霉素联合用药可产生一定的协同效应. 结论:LY294002通过下调Jur-katT细胞ICBP90蛋白的表达,抑制Jurkat T细胞增殖. 相似文献
227.
Suhre K Wallaschofski H Raffler J Friedrich N Haring R Michael K Wasner C Krebs A Kronenberg F Chang D Meisinger C Wichmann HE Hoffmann W Völzke H Völker U Teumer A Biffar R Kocher T Felix SB Illig T Kroemer HK Gieger C Römisch-Margl W Nauck M 《Nature genetics》2011,43(6):565-569
We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria. 相似文献
228.
Natural killer (NK) cells have originally been identified by their spontaneous cytolytic potential against tumor cells, which,
however, might result from pre-activation due to prior pathogen exposure. Resting NK cells, on the contrary, require activation
by bystander antigen-presenting cells to reach their full functional competence. In this review, we will summarize studies
on how dendritic cells (DCs), the most potent type of antigen-presenting cell, communicate with human NK cells to activate
them in secondary lymphoid organs and to integrate signals from activated NK cells at sites of inflammation for their own
maturation. Furthermore, we will review aspects of the immunological synapse, which mediates this cross-talk. These studies
provide the mechanistic understanding of how mature DCs can activate NK cells and survive to go on for the activation of adaptive
immunity. This feature of DCs, to activate different waves of immune responses, could be harnessed for immunotherapies, including
vaccinations. 相似文献
229.
Arking DE Pfeufer A Post W Kao WH Newton-Cheh C Ikeda M West K Kashuk C Akyol M Perz S Jalilzadeh S Illig T Gieger C Guo CY Larson MG Wichmann HE Marbán E O'Donnell CJ Hirschhorn JN Kääb S Spooner PM Meitinger T Chakravarti A 《Nature genetics》2006,38(6):644-651
Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP (CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation. 相似文献
230.
Löbel M Bauer S Meisel C Eisenreich A Kudernatsch R Tank J Rauch U Kühl U Schultheiss HP Volk HD Poller W Scheibenbogen C 《Cellular and molecular life sciences : CMLS》2012,69(18):3101-3113
In this study, we performed a comprehensive analysis of the effect of CCN1 on the migration of human immune cells. The molecule CCN1, produced by fibroblasts and endothelial cells, is considered as an important matrix protein promoting tissue repair and immune cell adhesion by binding various integrins. We recently reported that CCN1 therapy is able to suppress acute inflammation in vivo. Here, we show that CCN1 binds to various immune cells including T cells, B cells, NK cells, and monocytes. The addition of CCN1 in vitro enhances both actin polymerization and transwell migration. Prolonged incubation with CCN1, however, results in the inhibition of migration of immune cells by a mechanism that involves downregulation of PI3Kγ, p38, and Akt activation. Furthermore, we observed that immune cells themselves produce constitutively CCN1 and secretion is induced by pro-inflammatory stimuli. In line with this finding, patients suffering from acute inflammation had enhanced serum levels of CCN1. These findings extend the classical concept of CCN1 as a locally produced cell matrix adhesion molecule and suggest that CCN1 plays an important role in regulating immune cell trafficking by attracting and locally immobilizing immune cells. 相似文献