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181.
Telomere dysfunction may result in chromosomal abnormalities, DNA damage responses, and even cancer. Early studies in lower organisms have helped to establish the crucial role of telomerase and telomeric proteins in maintaining telomere length and protecting telomere ends. In Oxytricha nova, telomere G-overhangs are protected by the TEBP-alpha/beta heterodimer. Human telomeres contain duplex telomeric repeats with 3' single-stranded G-overhangs, and may fold into a t-loop structure that helps to shield them from being recognized as DNA breaks. Additionally, the TEBP-alpha homologue, POT1, which binds telomeric single-stranded DNA (ssDNA), associates with multiple telomeric proteins (for example, TPP1, TIN2, TRF1, TRF2 and RAP1) to form the six-protein telosome/shelterin and other subcomplexes. These telomeric protein complexes in turn interact with diverse pathways to form the telomere interactome for telomere maintenance. However, the mechanisms by which the POT1-containing telosome communicates with telomerase to regulate telomeres remain to be elucidated. Here we demonstrate that TPP1 is a putative mammalian homologue of TEBP-beta and contains a predicted amino-terminal oligonucleotide/oligosaccharide binding (OB) fold. TPP1-POT1 association enhanced POT1 affinity for telomeric ssDNA. In addition, the TPP1 OB fold, as well as POT1-TPP1 binding, seemed critical for POT1-mediated telomere-length control and telomere-end protection in human cells. Disruption of POT1-TPP1 interaction by dominant negative TPP1 expression or RNA interference (RNAi) resulted in telomere-length alteration and DNA damage responses. Furthermore, we offer evidence that TPP1 associates with the telomerase in a TPP1-OB-fold-dependent manner, providing a physical link between telomerase and the telosome/shelterin complex. Our findings highlight the critical role of TPP1 in telomere maintenance, and support a yin-yang model in which TPP1 and POT1 function as a unit to protect human telomeres, by both positively and negatively regulating telomerase access to telomere DNA. 相似文献
182.
Pandey UB Nie Z Batlevi Y McCray BA Ritson GP Nedelsky NB Schwartz SL DiProspero NA Knight MA Schuldiner O Padmanabhan R Hild M Berry DL Garza D Hubbert CC Yao TP Baehrecke EH Taylor JP 《Nature》2007,447(7146):859-863
A prominent feature of late-onset neurodegenerative diseases is accumulation of misfolded protein in vulnerable neurons. When levels of misfolded protein overwhelm degradative pathways, the result is cellular toxicity and neurodegeneration. Cellular mechanisms for degrading misfolded protein include the ubiquitin-proteasome system (UPS), the main non-lysosomal degradative pathway for ubiquitinated proteins, and autophagy, a lysosome-mediated degradative pathway. The UPS and autophagy have long been viewed as complementary degradation systems with no point of intersection. This view has been challenged by two observations suggesting an apparent interaction: impairment of the UPS induces autophagy in vitro, and conditional knockout of autophagy in the mouse brain leads to neurodegeneration with ubiquitin-positive pathology. It is not known whether autophagy is strictly a parallel degradation system, or whether it is a compensatory degradation system when the UPS is impaired; furthermore, if there is a compensatory interaction between these systems, the molecular link is not known. Here we show that autophagy acts as a compensatory degradation system when the UPS is impaired in Drosophila melanogaster, and that histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase that interacts with polyubiquitinated proteins, is an essential mechanistic link in this compensatory interaction. We found that compensatory autophagy was induced in response to mutations affecting the proteasome and in response to UPS impairment in a fly model of the neurodegenerative disease spinobulbar muscular atrophy. Autophagy compensated for impaired UPS function in an HDAC6-dependent manner. Furthermore, expression of HDAC6 was sufficient to rescue degeneration associated with UPS dysfunction in vivo in an autophagy-dependent manner. This study suggests that impairment of autophagy (for example, associated with ageing or genetic variation) might predispose to neurodegeneration. Morover, these findings suggest that it may be possible to intervene in neurodegeneration by augmenting HDAC6 to enhance autophagy. 相似文献
183.
Watson DM Bohac CJ Hull C Forrest WJ Furlan E Najita J Calvet N d'Alessio P Hartmann L Sargent B Green JD Kim KH Houck JR 《Nature》2007,448(7157):1026-1028
Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333-IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope. Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333-IRAS 4B a rich emission spectrum of H2O, at wavelengths 20-37 microm, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk. 相似文献
184.
徽州古村落形成与发展的地理环境研究 总被引:4,自引:0,他引:4
徽州地处亚热带湿润季风气候区,黄山、天目山和白际山脉环绕徽州四周,山脉之间形成休(宁)歙(县)、黟县、祁门等盆地,源于四周山脉的新安江及其众多支流回环全境,形成闭塞而景色秀美的自然环境,为历史上中原地区因战乱等原因形成的南迁人口提供了重要的迁徙地.大量中原人口的迁入,给徽州带来了封建宗法制度,促进了徽州的文风,同时也加剧了徽州的人地矛盾.明清时期的徽商,为徽州古村落的建设和发展奠定了坚实的物质基础.历经千百年的发展,“秀丽山水”、“文风昌盛”和“富甲天下”终于成为明清时期徽州古村落自然环境和人文环境的主要内涵. 相似文献
185.
该文提出结合粗糙集(RS)和最小二乘支持向量回归(LS-SVR)的方法.该方法利用RS对原始数据进行约简,更好地减少了支持向量的维数;同时采用LS-SVR解决了常规SVM计算速度慢、抗噪能力差的缺点.实例证明该方法应用在复杂地层储层参数预测中具有优越性. 相似文献
186.
数控装备质量的模糊物元综合评价方法 总被引:2,自引:2,他引:0
针对数控装备质量多层次指标评价问题,提出了一种基于模糊物元模型的综合评价方法。该方法利用模糊物元理论分析多个质量特性及其属性特征,并建立了数控装备质量综合评价模型。采用层次分析法和信息熵确定评价指标权重,建立基于最小二乘法的优化组合权重模型计算组合权重,并运用模糊物元法给出评价结果。实例研究表明该方法可行、合理。 相似文献
187.
张丹 《辽宁大学学报(自然科学版)》2011,38(1):22-26
电流互感器是电力系统中的重要设备,光电混合式电流互感器避免了传统电流互感器的缺点,具有广泛的应用前景.对光电混合式电流互感器做了具体的分析,提出了一种系统设计方案,并详细介绍了方案的具体实现方法.整个系统方案具有可行性,可以达到预想的要求,具有高集成度、高处理速度、高可靠性以及良好的实时性等优点,在电力系统中具有一定的研究价值与应用价值. 相似文献
188.
189.
提出了一种既能满足属性平衡又能有效处理相似属性模式的新方法——改进的极大化整体判别认知诊断模型信息量指标法(MGCDI).对无结构型的属性,讨论定长CD-CAT的选题策略.研究结果表明,使用相同选题策略选题时,先选择可达矩阵的所有列对应的项目比不使用这些项目的诊断准确率高. 相似文献
190.
不同热解温度生物炭改良铅和镉污染土壤的研究 总被引:5,自引:0,他引:5
为了探究热解温度对生物炭修复重金属污染土壤的影响,将300℃、500℃和700℃下制备的生物炭加入铅(Pb)和镉(Cd)污染土壤进行培养,检测重金属形态的变化。结果表明,加入生物炭培养60d后,Pb和Cd污染土壤pH值较对照上升0.35—0.86单位值,土壤中重金属的酸可提取态含量下降,残渣态含量上升,对目标重金属生物有效性降低的改良效果700℃>500℃>300℃;在生物炭添加量相同的情况下,复合污染土壤中Pb的残渣态含量比对应单一污染高50.60%—72.79%,而复合污染土壤中Cd的酸可提取态含量较对应单一污染高7.53%—12.99%;热解温度影响生物炭的表面特征和吸附重金属机制,进而影响生物炭改良土壤中目标重金属形态分布。 相似文献