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Chan TL Yuen ST Kong CK Chan YW Chan AS Ng WF Tsui WY Lo MW Tam WY Li VS Leung SY 《Nature genetics》2006,38(10):1178-1183
Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy. 相似文献
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As a smart combination of cognitive radio networks and wireless sensor networks, recently introduced cognitive radio sensor network (CRSN) poses new challenges to the design of topology maintenance techniques for dynamic primary-user activities. This paper aims to provide a solution to the energy-efficient spectrum-aware CRSN clustering problem. Specifically, we design the clustered structure, establish a network-wide energy consumption model and determine the optimal number of clusters. We then employ the ideas from constrained clustering and propose both a centralized spectrum-aware clustering algorithm and a distributed spectrum-aware clustering (DSAC) protocol. Through extensive simulations, we demonstrate that DSAC can effectively form clusters under a dynamic spectrum-aware constraint. Moreover, DSAC exhibits preferable scalability and stability with its low complexity and quick convergence under dynamic spectrum variation. 相似文献
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Twisted gastrulation can function as a BMP antagonist 总被引:5,自引:0,他引:5
Chang C Holtzman DA Chau S Chickering T Woolf EA Holmgren LM Bodorova J Gearing DP Holmes WE Brivanlou AH 《Nature》2001,410(6827):483-487
Bone morphogenetic proteins (BMPs), including the fly homologue Decapentaplegic (DPP), are important regulators of early vertebrate and invertebrate dorsal-ventral development. An evolutionarily conserved BMP regulatory mechanism operates from fly to fish, frog and mouse to control the dorsal-ventral axis determination. Several secreted factors, including the BMP antagonist chordin/Short gastrulation (SOG), modulate the activity of BMPs. In Drosophila, Twisted gastrulation (TSG) is also involved in dorsal-ventral patterning, yet the mechanism of its function is unclear. Here we report the characterization of the vertebrate Tsg homologues. We show that Tsg can block BMP function in Xenopus embryonic explants and inhibits several ventral markers in whole-frog embryos. Tsg binds directly to BMPs and forms a ternary complex with chordin and BMPs. Coexpression of Tsg with chordin leads to a more efficient inhibition of the BMP activity in ectodermal explants. Unlike other known BMP antagonists, however, Tsg also reduces several anterior markers at late developmental stages. Our data suggest that Tsg can function as a BMP inhibitor in Xenopus; furthermore, Tsg may have additional functions during frog embryogenesis. 相似文献
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Sinnarajah S Dessauer CW Srikumar D Chen J Yuen J Yilma S Dennis JC Morrison EE Vodyanoy V Kehrl JH 《Nature》2001,409(6823):1051-1055
The heterotrimeric G-protein Gs couples cell-surface receptors to the activation of adenylyl cyclases and cyclic AMP production (reviewed in refs 1, 2). RGS proteins, which act as GTPase-activating proteins (GAPs) for the G-protein alpha-subunits alpha(i) and alpha(q), lack such activity for alpha(s) (refs 3-6). But several RGS proteins inhibit cAMP production by Gs-linked receptors. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the alpha(s) family member alpha(olf) links odorant receptors to adenylyl cyclase activation. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on alpha(olf) but by inhibiting the activity of adenylyl cyclase type III, the predominant adenylyl cyclase isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively regulates odorant-evoked intracellular signalling. These results reveal a mechanism for controlling the activities of adenylyl cyclases, which probably contributes to the ability of olfactory neurons to discriminate odours. 相似文献
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Numerical modelling of geological processes, such as mantle convection, flow in porous media, and geothermal heat transfer, has become quite common with the increase in computing and the availability o... 相似文献
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以山西省晋中盆地为研究对象,对晋中盆地近18年的城市化发展及其对区域内河流的影响进行了研究,并用相关分析法对盆地内城市化率变化与河水中各种主要污染物之间的关系进行了分析.结果表明,虽然地表水中13种主要污染物质的质量浓度(ρ)在个别年份略有下降,但总体上呈现为持续增加的趋势.针对当地河流存在的问题,提出了生态修复的方法. 相似文献
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管道内甲烷-空气预混火焰传播特性的实验与数值模拟研究 总被引:2,自引:0,他引:2
采用高速纹影摄像系统、压力传感器等对小型水平封闭管道内甲烷-空气预混燃烧火焰的传播过程进行了实验研究,得到了火焰锋面结构、传播速度和压力随时间的变化关系.研究结果表明,管道内预混火焰传播过程中,火焰结构会发生明显变化,即从向未燃气体凸出的球形层流火焰转变成向已燃气体凹陷的V形湍流火焰,同时伴有火焰传播速度的减小、压力的不断增大.另外运用标准k-ε模型,对非定常时的甲烷预混燃烧火焰进行数值模拟,得到了与实验结果类似的火焰传播特性和火焰结构的变化规律. 相似文献
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采用盆栽试验研究了铅胁迫条件下,不锈钢尾渣与腐殖酸配施对黑麦草叶片中可溶性蛋白含量、过氧化物酶(POD)活性、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量的影响。结果表明,不锈钢尾渣+腐殖酸在一定程度上降低黑麦草叶片可溶性蛋白含量,抑制黑麦草的代谢活动,且在不锈钢尾渣+腐殖酸施加量为5%时抑制作用最强。在未污染土壤中,随着不锈钢尾渣+腐殖酸施加量的增加,黑麦草叶片中SOD活性先升高后降低,POD活性逐渐升高,MDA含量降低;在高浓度铅胁迫(2 000mg/kg)下,不锈钢尾渣+腐殖酸对黑麦草叶片SOD和POD起到激活作用,可有效清除黑麦草叶片内过多的活性自由基,减轻铅胁迫。在铅胁迫条件下,过量(5%)施加不锈钢尾渣+腐殖酸会促进黑麦草叶片脂膜过氧化作用,加重叶片细胞老化程度。 相似文献