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Specific activity of glutamine synthetase in Squalus acanthias (spiny dogfish) central nervous system regions was highest in the cerebellum and lowest in the spinal cord. The levels of activity may relate to the excitability of each region by regulating the glutamate pool. 相似文献
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KI Cho K Searle M Webb H Yi PA Ferreira 《Cellular and molecular life sciences : CMLS》2012,69(20):3511-3527
Many components and pathways transducing multifaceted and deleterious effects of stress stimuli remain ill-defined. The Ran-binding protein 2 (RanBP2) interactome modulates the expression of a range of clinical and cell-context-dependent manifestations upon a variety of stressors. We examined the role of Ranbp2 haploinsufficiency on cellular and metabolic manifestations linked to tyrosine-hydroxylase (TH(+)) dopaminergic neurons and glial cells of the brain and retina upon acute challenge to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonian neurotoxin, which models facets of Parkinson disease. MPTP led to stronger akinetic parkinsonism and slower recovery in Ranbp2 (+/-) than wild-type mice without viability changes of brain TH(+)-neurons of either genotype, with the exception of transient nuclear atypia via changes in chromatin condensation of Ranbp2 (+/-) TH(+)-neurons. Conversely, the number of wild-type retinal TH(+)-amacrine neurons compared to Ranbp2 (+/-) underwent milder declines without apoptosis followed by stronger recoveries without neurogenesis. These phenotypes were accompanied by a stronger rise of EdU(+)-proliferative cells and non-proliferative gliosis of GFAP(+)-Müller cells in wild-type than Ranbp2 (+/-) that outlasted the MPTP-insult. Finally, MPTP-treated wild-type and Ranbp2 (+/-) mice present distinct metabolic footprints in the brain or selective regions thereof, such as striatum, that are supportive of RanBP2-mediated regulation of interdependent metabolic pathways of lysine, cholesterol, free-fatty acids, or their β-oxidation. These studies demonstrate contrasting gene-environment phenodeviances and roles of Ranbp2 between dopaminergic and glial cells of the brain and retina upon oxidative stress-elicited signaling and factors triggering a continuum of metabolic and cellular manifestations and proxies linked to oxidative stress, and chorioretinal and neurological disorders such as Parkinson. 相似文献
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Giardine B Borg J Higgs DR Peterson KR Philipsen S Maglott D Singleton BK Anstee DJ Basak AN Clark B Costa FC Faustino P Fedosyuk H Felice AE Francina A Galanello R Gallivan MV Georgitsi M Gibbons RJ Giordano PC Harteveld CL Hoyer JD Jarvis M Joly P Kanavakis E Kollia P Menzel S Miller W Moradkhani K Old J Papachatzopoulou A Papadakis MN Papadopoulos P Pavlovic S Perseu L Radmilovic M Riemer C Satta S Schrijver I Stojiljkovic M Thein SL Traeger-Synodinos J Tully R Wada T Waye JS Wiemann C 《Nature genetics》2011,43(4):295-301
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases. 相似文献
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Axial volcano, which is located near the intersection of the Juan de Fuca ridge and the Cobb-Eickelberg seamount chain beneath the northeast Pacific Ocean, is a locus of volcanic activity thought to be associated with the Cobb hotspot. The volcano rises 700 metres above the ridge, has substantial rift zones extending about 50 kilometres to the north and south, and has erupted as recently as 1998 (ref. 2). Here we present seismological data that constrain the three-dimensional velocity structure beneath the volcano. We image a large low-velocity zone in the crust, consisting of a shallow magma chamber and a more diffuse reservoir in the lower crust, and estimate the total magma volume in the system to be between 5 and 21 km3. This volume is two orders of magnitude larger than the amount of melt emplaced during the most recent eruption (0.1-0.2 km3). We therefore infer that such volcanic events remove only a small portion of the reservoir that they tap, which must accordingly be long-lived compared to the eruption cycle. On the basis of magma flux estimates, we estimate the crustal residence time of melt in the volcanic system to be a few hundred to a few thousand years. 相似文献
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RhoA/Rho激酶在大鼠阴茎勃起机制中的调节作用 总被引:11,自引:1,他引:10
一般认为一氧化氮(nitric oxide,NO)释放增加促进小动脉和海绵体平滑肌舒张是导致男性阴茎勃起的主要机制。研究发现内源性血管收缩因子对维持阴茎萎状态有重要作用。应用大鼠模型活体检测使用Y-27632拮抗Rho-激酶活性后对阴茎勃起生理机制的影响;应用免疫转印技术检测 阴茎海绵体内RhoA和Rho激酶蛋白的表达。结果显示在大鼠海绵体组织内有内源性RhoA和Rho激酶蛋白的表达和存在;Y-27632海绵体内注射阻滞RhoA/Rho激酶活性使ICP和CCP/MAP比值明显升高;局部小剂量应用Y-27632对MAP没有明显影响;Y-27632可增强系列电刺激引起的由NO介导的CCP/MAP比值的增加;NO合成酶和鸟苷酸环化酶抑制剂的作用不能阻滞RhoA/Rho激酶抑制剂对大鼠阴茎海绵体平滑肌的松弛作用和CCP/MAP的增加。说明RhoA/Rho激酶信号系统发挥了维持海绵体萎软状态重要作用,这是与NO介导途径不同的阴茎勃起生理调节机制。RhoA/Rho激酶抑制剂可能是ED治疗的新领域新方法。 相似文献
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