2,165 research outputs found
Regulation of System XC- and its Contribution to Cell Death
Full text linkThe main focus of the studies in this thesis involves examining the role of cystine/glutamate exchange (system xC-) in neuronal death in primary cortical cell culture, with an emphasis on how glial function affects neuronal cell death. System xC- is a sodium-independent transporter that mediates cystine uptake and glutamate release. It accounts for most of the cystine uptake in astrocytes in mature cultures, providing the rate limiting substrate for synthesis of the main endogenous antioxidant glutathione. The glutamate released by system xC- may lead to excessive extracellular glutamate and cause excitotoxicity.
β-N-methylamino-L-alanine (BMAA) is a non-protein amino acid that may be involved in neurodegenerative diseases. We found that BMAA induced oxidative stress by competing with cystine at system xC- leading to depletion of glutathione. BMAA also drives system xC- mediated glutamate release, which may contribute to its induction of excitotoxicity.
Fibroblast growth factor-2 (FGF-2) is involved in multiple processes in the central nervous system, including plasticity, neurogenesis, differentiation, and neuronal survival. Also, alterations in FGF-2 and its signaling have been implicated in neurodegenerative diseases and psychiatric disorders. We found that FGF-2 greatly increased cystine uptake through system xC- in astrocyte-enriched primary cultures, but not in neuronal or microglial cultures. Our data showed that FGF-2 increased cystine uptake by upregulating system xC- by acting on FGFR1, and signaling through the PI3K/Akt and MEK/ERK pathways.
FGF-2 treatment for 48 hours caused significant neuronal death only in mixed neuronal and glial cultures, but not in neuronal-enriched or astrocyte-enriched cultures. Blocking system xC-, or AMPA/kainate receptors, eliminated the neuronal death induced by FGF-2 treatment. Therefore, it is likely that 48 hour FGF-2 treatment induces AMPA receptor mediated toxicity through increased glutamate release from astrocytes due to increased system xC- function. However, we cannot exclude the possibility that FGF-2 treatment sensitizes the neurons to normal system xC- mediated glutamate release.
Together the results indicate that 1) competitive substrates of system xC-, such as BMAA, that do not lead to glutathione production are particularly toxic; and 2) upregulation of system xC- on astrocytes may be toxic to surrounding neurons
Late Pan-African granitoids from the Grove Mountains, East Antarctica: Age, origin and tectonic implications
No full textMesozoic adakites in the Lingqiu Basin of the central North China Craton: Partial melting of underplated basaltic lower crust
No full textSynthesis and magnetic properties of melt-spun high Pr-content magnetostrictive alloys
No full textPseudobinary high Pr-content Tb1-xPrx(Fe0.4Co0.6)(1.93) (0.70 = 35m/s and subsequent annealing at 500 degrees C for 30 min. The lattice parameter of the Tb1-xPrx(Fe0.4Co0.6)(1.93) Laves phase increases from 0.7354 nm for x = 0.70 to 0.7384 nm for x = 1.00 and approximately follows the linear Vegard's law. The Curie temperature decreases, while the saturation magnetization increases as increasing Pr content. The Pr-rich alloys possess the relatively lower coercivity and the faster saturation of magnetostriction as compared with the Tb-rich alloys, which can be understood by their lower magnetic anisotropy. (C) 2009 Published by Elsevier B.V
FGF-2 Induces Neuronal Death through Upregulation of System xc-
Full text linkThe cystine/glutamate antiporter (system xc-) transports cystine into cell in exchange for glutamate. Fibroblast growth factor-2 (FGF-2) upregulates system xc- selectively on astrocytes, which leads to increased cystine uptake, the substrate for glutathione production, and increased glutamate release. While increased intracellular glutathione can limit oxidative stress, the increased glutamate release can potentially lead to excitotoxicity to neurons. To test this hypothesis, mixed neuronal and glial cortical cultures were treated with FGF-2. Treatment with FGF-2 for 48 h caused a significant neuronal death in these cultures. Cell death was not observed in neuronal-enriched cultures, or astrocyte-enriched cultures, suggesting the toxicity was the result of neuron-glia interaction. Blocking system xc- eliminated the neuronal death as did the AMPA/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), but not the NMDA receptor antagonist memantine. When cultures were exposed directly to glutamate, both NBQX and memantine blocked the neuronal toxicity. The mechanism of this altered profile of glutamate receptor mediated toxicity by FGF-2 is unclear. The selective calcium permeable AMPA receptor antagonist 1-naphthyl acetyl spermine (NASPM) failed to offer protection. The most likely explanation for the results is that 48 h FGF-2 treatment induces AMPA/kainate receptor toxicity through increased system xc- function resulting in increased release of glutamate. At the same time, FGF-2 alters the sensitivity of the neurons to glutamate toxicity in a manner that promotes selective AMPA/kainate receptor mediated toxicity
Structure and magnetostrictive properties of melt-spun Pr(Fe0.4Co0.6)(1.93) alloys
No full textPr( Fe0.4Co0.6)(1.93) ribbons were prepared by a melt-spinning method. Their structure and magnetic properties are investigated as functions of wheel speed and annealing temperature. The as-spun ribbon consists of a Pr(Fe, Co)(2) cubic Laves phase and an amorphous phase at a wheel speed of v >= 35m/s, while the non-cubic phases of PuNi3-type and rare earth appear when the speed lower than 30m/s. A single Pr(Fe, Co)(2) phase with MgCu2-type structure has been synthesized by the process for the wheel speed of v >= 35 m/s and subsequent annealing at 500 degrees C for 30 min. The epoxy/Pr(Fe0.4Co0.6)(1.93) composite has been produced by a cold isostatic pressing technique, and the magnetic properties have been investigated. The composite rod sample possesses good magnetostrictive properties, i.e., a large magnetostriction (lambda(a) = lambda(parallel to) - lambda(perpendicular to)) of 710 ppm at 800 kA/m and a dynamic coefficient d(33) of 0.67nm/ Aat 100 kA/m, and is of practical value. (C) 2009 Published by Elsevier B.V
A cohort study of behavioral problems and intelligence in children with high prenatal polychlorinated biphenyls exposure.
No full textQuantum dynamical R-matrix from fusion
No full textA quantum dynamical R-matrix (QDRM) with three distinct eigenvalues, which is a trigonometric solution of the Gervais-Neven-Felder equation, is constructed from the fusion of the simplest 4 x 4 trigonometric QDRM of Hecke type for sl(2).Physics, MultidisciplinarySCI(E)中国科学引文数据库(CSCD)1ARTICLE1157-1603
通过基于多肽酰肼的化学连接反应合成高张力环状四肽
No full textA series of highly-strained cyclic tetrapeptides were efficiently synthesized via peptide hydrazide based ligation, reported by Liu et al. Upon mild oxidative activation, the peptide hydrazide was transformed into a highly active peptide azide intermediate and then in situ converted into a peptide 4-mercaptophenylacetic acid (MPAA) thiol ester, which underwent native chemical ligation (NCL)-mediated cyclization to afford the desired cyclic tetrapeptides. After radical desulfurization, the product with alanine residue at the ligation site can be obtained.link_to_OA_fulltex
Study on Performance Management System of XC Company
Full text link在我国，推行绩效管理工作的企业越来越多，但取得良好效果的却并不多，本文针对我国中小企业的特点，通过对笔者工作的XC公司绩效管理工作实践的研究和分析，对企业如何建立和运行有效的绩效管理体系进行了深入的探讨，提出了很多有益的建议和方法，全文共分四章，主要内容包括：第一部分从理论上概述了绩效管理工作的基本涵义和过程内容，介绍目前企业绩效管理工作的几种主要模式及其特点，并就绩效管理工作中应坚持的核心理念进行了分析和说明。第二部分介绍了XC公司所处的行业背景和企业本身面对的市场环境，对XC公司现行绩效管理工作所存在的问题及其成因进行了分析和讨论。第三部分主要针对XC公司所存在的问题提出绩效管理体系的改善...In China, many enterprises tried to adopt performance management system, while few of them really benefited from it. The author, with several years’ experience of performance management in XC company, explicates his view that how the enterprises should set up a constructive performance management and further carry out the management system. In the article, the author puts forward a few instructi...学位：管理学硕士院系专业：管理学院工商管理教育中心_工商管理硕士(MBA)学号：X20001501
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