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81.
Micu I Jiang Q Coderre E Ridsdale A Zhang L Woulfe J Yin X Trapp BD McRory JE Rehak R Zamponi GW Wang W Stys PK 《Nature》2006,439(7079):988-992
Central nervous system myelin is a specialized structure produced by oligodendrocytes that ensheaths axons, allowing rapid and efficient saltatory conduction of action potentials. Many disorders promote damage to and eventual loss of the myelin sheath, which often results in significant neurological morbidity. However, little is known about the fundamental mechanisms that initiate myelin damage, with the assumption being that its fate follows that of the parent oligodendrocyte. Here we show that NMDA (N-methyl-d-aspartate) glutamate receptors mediate Ca2+ accumulation in central myelin in response to chemical ischaemia in vitro. Using two-photon microscopy, we imaged fluorescence of the Ca2+ indicator X-rhod-1 loaded into oligodendrocytes and the cytoplasmic compartment of the myelin sheath in adult rat optic nerves. The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptor antagonist NBQX completely blocked the ischaemic Ca2+ increase in oligodendroglial cell bodies, but only modestly reduced the Ca2+ increase in myelin. In contrast, the Ca2+ increase in myelin was abolished by broad-spectrum NMDA receptor antagonists (MK-801, 7-chlorokynurenic acid, d-AP5), but not by more selective blockers of NR2A and NR2B subunit-containing receptors (NVP-AAM077 and ifenprodil). In vitro ischaemia causes ultrastructural damage to both axon cylinders and myelin. NMDA receptor antagonism greatly reduced the damage to myelin. NR1, NR2 and NR3 subunits were detected in myelin by immunohistochemistry and immunoprecipitation, indicating that all necessary subunits are present for the formation of functional NMDA receptors. Our data show that the mature myelin sheath can respond independently to injurious stimuli. Given that axons are known to release glutamate, our finding that the Ca2+ increase was mediated in large part by activation of myelinic NMDA receptors suggests a new mechanism of axo-myelinic signalling. Such a mechanism may represent a potentially important therapeutic target in disorders in which demyelination is a prominent feature, such as multiple sclerosis, neurotrauma, infections (for example, HIV encephalomyelopathy) and aspects of ischaemic brain injury. 相似文献
82.
Haislip JB Nysewander MC Reichart DE Levan A Tanvir N Cenko SB Fox DB Price PA Castro-Tirado AJ Gorosabel J Evans CR Figueredo E MacLeod CL Kirschbrown JR Jelinek M Guziy S de Ugarte Postigo A Cypriano ES LaCluyze A Graham J Priddey R Chapman R Rhoads J Fruchter AS Lamb DQ Kouveliotou C Wijers RA Bayliss MB Schmidt BP Soderberg AM Kulkarni SR Harrison FA Moon DS Gal-Yam A Kasliwal MM Hudec R Vitek S Kubanek P Crain JA Foster AC Clemens JC Bartelme JW Canterna R Hartmann DH Henden AA Klose S 《Nature》2006,440(7081):181-183
Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe. 相似文献
83.
Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. 总被引:33,自引:0,他引:33
V O Ona M Li J P Vonsattel L J Andrews S Q Khan W M Chung A S Frey A S Menon X J Li P E Stieg J Yuan J B Penney A B Young J H Cha R M Friedlander 《Nature》1999,399(6733):263-267
Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex. The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease. Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease. 相似文献
84.
85.
基于钻进过程监测系统在充填土-风化花岗岩地层中对液压旋转钻进的监测数据,对金刚石钻进系统的能量进行了分析.结果表明,钻进系统的能量分布与在普通风化花岗岩地层中的结果一致,黏滞能、动能以及钻进总能量与岩石的风化程度呈负相关,轴力功与岩石的风化程度呈正相关,说明金刚石钻进能量与岩石风化程度具有很好的响应关系.动能、轴力功及黏滞能受钻进方式影响,用于地层识别将受严格的可比条件限制.金刚石钻进比功随岩石风化程度的增强而减少,在不同风化程度的岩层中具有很好的分区性.而且,在充填土及全风化、强风化花岗岩地层中,金刚石旋转钻进比功值明显低于冲击凿碎比功,在微风化的坚硬岩中,旋转钻进比功则明显高于冲击凿碎比功. 相似文献
86.
卫星编队飞行的轨道和姿态GPS自主同步反馈控制 总被引:1,自引:0,他引:1
鉴于编队飞行之中卫星不但对轨道有要求,而且对姿态也有要求,例如有的编队飞行卫星在惯性空间中有指向控制的要求,或者相互之间有保持一定的姿态关系的要求,同时在轨道控制过程中也需要姿态信息,因此在编队飞行的建立过程中,需要考虑姿态和轨道的协调控制和同步控制问题.本文提出了用汗同步控制的相对轨道和相对姿态运动学和动力学模型、控制率的选择和设计以及用GPS的伪距和载波相位实现轨道和姿态同步实时反馈控制方法.其中包括用修改的Kodrigues参数实现无奇异的大姿态机动的非线性状态跟踪控制.对EO-1/Landsat 7编队飞行的同步控制进行了数字仿真,证实了设计的正确性和实现的可行性. 相似文献
87.
88.
含油污泥微生物堆制处理研究 总被引:4,自引:0,他引:4
采用微生物堆制法对延长油田含油污泥进行处理,以除油率为指标,分别研究了不同菌种、接种量、调理剂及堆制时间等因素对处理效果的影响.结果表明:增加堆制时间与接种量,除油率提高.经过35 d堆制处理,YC-1菌与YC-13菌的除油率分别达43.41%和54.02%.YC-1菌采用土作为调理剂时除油率为40.01%,优于采用土+荞麦皮的19.05%,而YC-3菌采用土+荞麦皮作为调理剂时除油率为32.55%,略优于采用土作为调理剂的25.38%. 相似文献
89.
大气降水中低分子有机酸的季节变化及对酸雨形成的贡献(以贵阳市和尚重镇为例) 总被引:4,自引:0,他引:4
低分子有机酸是大气中普遍存在的一种化学成分, 对酸雨的形成有重要的贡献. 西南地区是酸雨污染重灾区, 2006年4月到2007年4月用离子色谱法测定了贵阳市和尚重镇大气降水中的7种低分子有机酸. 实验结果表明: 两地大气降水中, 甲酸、乙酸和草酸是最主要的有机酸, 贵阳市其雨量加权平均值分别为14.24, 9.35和2.79 μmol/L, 而尚重镇则分别为4.95, 1.35和2.31 μmol/L. 尚重镇大气降水中低分子有机酸生长季节浓度高于非生长季节浓度, 说明植物或土壤的释放可能是尚重镇大气有机酸的主要来源; 与之相反, 贵阳市大气降水中有机酸非生长季节浓度高于生长季节浓度, 可能与该地区冬季降水次数少, 每次雨量小以及降水同时易伴随颗粒物沉降有关. 贵阳市有机酸对自由酸贡献分别为: 甲酸?7.9%, 乙酸?4.7%, 草酸?6.1%, 3种主要有机酸贡献了18.7%的自由酸; 尚重镇分别为: 甲酸?25.1%, 乙酸?7.5%, 草酸?25.5%, 有机酸对自由酸贡献为58.1%. 贵阳市降水中有机酸根占阴离子总和的1.7%~19.2%, 平均值为6.6%. 尚重镇降水中有机酸根对总阴离子的贡献为0.5%~92.2%, 平均贡献为13.2%. 由此可见, 低分子有机酸, 尤其是边远地区, 对大气降水酸化的影响不可忽视. 相似文献
90.
用时域有限差分方法(finite-difference time-domain,FDTD)模拟了有不同局域等离激元共振频率和不同体积的外来金纳米颗粒以及外来介质纳米颗粒与金纳米棒的耦合,研究了正入射条件下与各种颗粒耦合对诱发金棒上纵向等离激元的禁戒模式的不同影响,发现外来颗粒上足够多的电荷积聚造成的电场对称性破缺是诱发禁戒模式的原因.这一发现对理解金属纳米颗粒的近场光学实验探测有重要意义. 相似文献