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In the present study we demonstrated that neurotoxin MPP+-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP+-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G0/G1 cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP+ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP+ and cell-cycle re-entry through retinoblastoma protein phosphorylation.  相似文献   
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In the Jurassic period, the Early Toarcian oceanic anoxic event (about 183 million years ago) is associated with exceptionally high rates of organic-carbon burial, high palaeotemperatures and significant mass extinction. Heavy carbon-isotope compositions in rocks and fossils of this age have been linked to the global burial of organic carbon, which is isotopically light. In contrast, examples of light carbon-isotope values from marine organic matter of Early Toarcian age have been explained principally in terms of localized upwelling of bottom water enriched in 12C versus 13C (refs 1,2,5,6). Here, however, we report carbon-isotope analyses of fossil wood which demonstrate that isotopically light carbon dominated all the upper oceanic, biospheric and atmospheric carbon reservoirs, and that this occurred despite the enhanced burial of organic carbon. We propose that--as has been suggested for the Late Palaeocene thermal maximum, some 55 million years ago--the observed patterns were produced by voluminous and extremely rapid release of methane from gas hydrate contained in marine continental-margin sediments.  相似文献   
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Thordarson P  Bijsterveld EJ  Rowan AE  Nolte RJ 《Nature》2003,424(6951):915-918
Nature has evolved complex enzyme architectures that facilitate the synthesis and manipulation of the biopolymers DNA and RNA, including enzymes capable of attaching to the biopolymer substrate and performing several rounds of catalysis before dissociating. Many of these 'processive' enzymes have a toroidal shape and completely enclose the biopolymer while moving along its chain, as exemplified by the DNA enzymes T4 DNA polymerase holoenzyme and lambda-exonucleoase. The overall architecture of these systems resembles that of rotaxanes, in which a long molecule or polymer is threaded through a macrocycle. Here we describe a rotaxane that mimics the ability of processive enzymes to catalyse multiple rounds of reaction while the polymer substrate stays bound. The catalyst consists of a substrate binding cavity incorporating a manganese(III) porphyrin complex that oxidizes alkenes within the toroid cavity, provided a ligand has been attached to the outer face of the toroid to both activate the porphyrin complex and shield it from being able to oxidize alkenes outside the cavity. We find that when threaded onto a polybutadiene polymer strand, this catalyst epoxidizes the double bonds of the polymer, thereby acting as a simple analogue of the enzyme systems.  相似文献   
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Pall P  Aina T  Stone DA  Stott PA  Nozawa T  Hilberts AG  Lohmann D  Allen MR 《Nature》2011,470(7334):382-385
Interest in attributing the risk of damaging weather-related events to anthropogenic climate change is increasing. Yet climate models used to study the attribution problem typically do not resolve the weather systems associated with damaging events such as the UK floods of October and November 2000. Occurring during the wettest autumn in England and Wales since records began in 1766, these floods damaged nearly 10,000 properties across that region, disrupted services severely, and caused insured losses estimated at £1.3 billion (refs 5, 6). Although the flooding was deemed a 'wake-up call' to the impacts of climate change at the time, such claims are typically supported only by general thermodynamic arguments that suggest increased extreme precipitation under global warming, but fail to account fully for the complex hydrometeorology associated with flooding. Here we present a multi-step, physically based 'probabilistic event attribution' framework showing that it is very likely that global anthropogenic greenhouse gas emissions substantially increased the risk of flood occurrence in England and Wales in autumn 2000. Using publicly volunteered distributed computing, we generate several thousand seasonal-forecast-resolution climate model simulations of autumn 2000 weather, both under realistic conditions, and under conditions as they might have been had these greenhouse gas emissions and the resulting large-scale warming never occurred. Results are fed into a precipitation-runoff model that is used to simulate severe daily river runoff events in England and Wales (proxy indicators of flood events). The precise magnitude of the anthropogenic contribution remains uncertain, but in nine out of ten cases our model results indicate that twentieth-century anthropogenic greenhouse gas emissions increased the risk of floods occurring in England and Wales in autumn 2000 by more than 20%, and in two out of three cases by more than 90%.  相似文献   
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综述长时间、大强度运动前、中、以及运动后恢复期间不同血糖指数的含碳水化合物(CHO)食物的补充对耐力运动能力及代谢的影响,目的在于为教练员、运动员及体育科研人员提供更为有益的运动营养补充方式,使营养补充与提高运动能力之间的关系达到更加优化的程度。  相似文献   
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针对CH4这种特别气体,对其实验结果运用数字化处理方法研究CH4稳定性.在内径50.8 mm圆形管道内获得CH4+2O2预混气在不同初始压力条件下的胞格爆轰结果并使用烟膜记录,且测得的平均爆轰速度数据与CJ爆轰速度接近,在初始压力高于5 kPa时爆轰可稳定传播.烟膜上形成的三波点轨迹十分不规则.为减少人为误差,使用改进后的数字化处理烟膜图像的技术方法,从烟膜轨迹中得出柱状图及自相关函数结果,发现CH4+2O2是一种爆轰十分不稳定的气体,并给出CH4+2O2预混气的爆轰胞格尺寸及差距,结果显示人为测量结果偏大而数字化处理方法更为准确.这种方法能计算CH4+2O2预混气胞格尺寸及不稳定度,完善了定量化预混气不稳定程度的方法.  相似文献   
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