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71.
老化是血管性疾病的主要危险因素之一.在老化过程中,内皮功能失调、基质金属蛋白酶调控失常、炎症分子表达增加、氧化应激增加和端粒长度缩短等因素引起了管腔扩张、内膜中层厚度改变等血管结构和僵硬度增加等功能的改变.这些改变使得冠状动脉粥样硬化性心脏病、原发性高血压、脑卒中等与年龄相关的血管性疾病易于发生.因此,抑制年龄相关的分子表达可能是干预血管性疾病的有效途径.哺乳动物SIRT1是一种NAD+依赖的组蛋白去乙酰化酶.近年来,对于SIRT1在血管性疾病中的作用受到广泛关注.本文结合我们的研究,阐述了SIRT1在血管老化及相关疾病中的作用,并提出SIRT1可能成为治疗动脉粥样硬化等年龄相关血管性疾病的潜在靶点. 相似文献
72.
针对地理位置路由中数据包的平均传输能耗随时间推移急剧增加的问题,设计并实现了一种基于两跳邻居信息量化的能量平衡路由协议(TNEB).节点通过Hello报文获得两跳范围内的邻居节点信息,TNEB根据两跳邻居信息确定一个贪婪转发候选节点集合.依据邻居节点的数据流拥塞度和能量平衡度,从候选节点集合中选择最佳的邻居节点完成数据包的转发.测试结果表明,在平均邻居节点数为15的网络拓扑上,TNEB算法的平均能耗比Greedy-2和GPSR算法分别降低了26.7%和48.8%,端到端延迟分别减少了19.9%和31.8%. 相似文献
73.
Broadhead R Dawe HR Farr H Griffiths S Hart SR Portman N Shaw MK Ginger ML Gaskell SJ McKean PG Gull K 《Nature》2006,440(7081):224-227
The 9 + 2 microtubule axoneme of flagella and cilia represents one of the most iconic structures built by eukaryotic cells and organisms. Both unity and diversity are present among cilia and flagella on the evolutionary as well as the developmental scale. Some cilia are motile, whereas others function as sensory organelles and can variously possess 9 + 2 and 9 + 0 axonemes and other associated structures. How such unity and diversity are reflected in molecular repertoires is unclear. The flagellated protozoan parasite Trypanosoma brucei is endemic in sub-Saharan Africa, causing devastating disease in humans and other animals. There is little hope of a vaccine for African sleeping sickness and a desperate need for modern drug therapies. Here we present a detailed proteomic analysis of the trypanosome flagellum. RNA interference (RNAi)-based interrogation of this proteome provides functional insights into human ciliary diseases and establishes that flagellar function is essential to the bloodstream-form trypanosome. We show that RNAi-mediated ablation of various proteins identified in the trypanosome flagellar proteome leads to a rapid and marked failure of cytokinesis in bloodstream-form (but not procyclic insect-form) trypanosomes, suggesting that impairment of flagellar function may provide a method of disease control. A postgenomic meta-analysis, comparing the evolutionarily ancient trypanosome with other eukaryotes including humans, identifies numerous trypanosome-specific flagellar proteins, suggesting new avenues for selective intervention. 相似文献
74.
Maier WD Andreoli MA McDonald I Higgins MD Boyce AJ Shukolyukov A Lugmair GW Ashwal LD Gräser P Ripley EM Hart RJ 《Nature》2006,441(7090):203-206
Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth. 相似文献
75.
76.
Pressor and tachycardic effects induced in the cat by stimulation of a lateral hypothalamic (LH) site, are shown to be mediated by sympathetic ganglia nicotinic receptor, and potentiated under atropine methyl nitrate sympathetic ganglia blockage. It is postulated that a sympatho-inhibitory pathway muscarinic ganglionic mechanism, co-activated by the LH stimulation, attenuates the pressor and tachycardic effects, the potentiation presumably being a manifestation of blockage of that mechanism. 相似文献
77.
Gene expression profiling predicts clinical outcome of breast cancer 总被引:243,自引:0,他引:243
van 't Veer LJ Dai H van de Vijver MJ He YD Hart AA Mao M Peterse HL van der Kooy K Marton MJ Witteveen AT Schreiber GJ Kerkhoven RM Roberts C Linsley PS Bernards R Friend SH 《Nature》2002,415(6871):530-536
Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy. 相似文献
78.
79.
A common feature of Drosophila homoeo box genes appears to be their spatially restricted expression patterns during morphogenesis. Using Northern blot analysis and in situ hybridization to mouse tissue sections, the spatially restricted expression of a newly identified mouse homoeo box locus, Hox-3, within the central nervous system of newborn and adult mice has been demonstrated. 相似文献
80.
A role for <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine as a nutrient sensor and mediator of insulin resistance 总被引:4,自引:0,他引:4
The ability to regulate energy balance at both the cellular and whole body level is an essential process of life. As western
society has shifted to a higher caloric diet and more sedentary lifestyle, the incidence of type 2 diabetes (non-insulin-dependent
diabetes mellitus) has increased to epidemic proportions. Thus, type 2 diabetes has been described as a disease of 'chronic
overnutrition'. There are abundant data to support the relationship between nutrient availability and insulin action. However,
there have been multiple hypotheses and debates as to the mechanism by which nutrient availability modulates insulin signaling
and how excess nutrients lead to insulin resistance. One well-established pathway for nutrient sensing is the hexosamine biosynthetic
pathway (HSP), which produces the acetylated aminosugar nucleotide uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc) as its end product. Since UDP-GlcNAc is the donor substrate for modification of nucleocytoplasmic
proteins at serine and threonine residues with N-acetylglucosamine (O-GlcNAc), the possibility of this posttranslational modification serving as the nutrient sensor has been proposed. We have
recently directly tested this model in adipocytes by examining the effect of elevated levels of O-GlcNAc on insulin-stimulated glucose uptake. In this review, we summarize the existing work that implicates the HSP and O-GlcNAc modification as nutrient sensors and regulators of insulin signaling.
RID="*"
ID="*"Corresponding author. 相似文献