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11.
Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived from cortex of Alzheimer's disease patients 总被引:4,自引:0,他引:4
Estrogen is thought to play a protective role against neurodegeneration through a variety of mechanisms including the activation of growth factors, the control of synaptic plasticity, and the reduction of response to various insults, such as iron and glutamate. Increasing evidence indicates an increased level of extracellular glutamate and a down-regulation of glutamate transporters in Alzheimer's disease (AD). In this study, we show that glutamate uptake in astrocytes derived from Alzheimer's patients is significantly lower than that from non-demented controls. Estrogen treatment increases glutamate uptake in a dose-dependent pattern. Two glutamate transporters, GLT-1 and GLAST, are expressed in the astrocytes. Up-regulation of the glutamate transporters is induced by estrogen treatment in AD astrocytes only. Our data suggest that the action of estrogen on glutamate uptake by astrocytes might contribute to its potential neuroprotective role in AD. 相似文献
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Jacobs SA Harp JM Devarakonda S Kim Y Rastinejad F Khorasanizadeh S 《Nature structural biology》2002,9(11):833-838
The SET domain contains the catalytic center of lysine methyltransferases that target the N-terminal tails of histones and regulate chromatin function. Here we report the structure of the SET7/9 protein in the absence and presence of its cofactor product, S-adenosyl-L-homocysteine (AdoHcy). A knot within the SET domain helps form the methyltransferase active site, where AdoHcy binds and lysine methylation is likely to occur. A structure-guided comparison of sequences within the SET protein family suggests that the knot substructure and active site environment are conserved features of the SET domain. 相似文献
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A number of ophiostomatoid fungi were isolated from the spruce-infesting bark beetle, Ips perturbatus and its galleries collected from felled spruce trees and logs in northern BC and the Yukon Territory. Isolates were identified to species using morphological characteristics, nuclear ribosomal DNA and partial β-tubulin gene sequences. Thirteen morphological and phylogenetic species were identified among the isolates. Leptographium fruticetum, Leptographium abietinum, Ophiostoma bicolor, Ophiostoma manitobense, O. piceaperdum, and eight undescribed species of the genus Ophiostoma and the anamorph genera Leptographium, Hyalorhinocladiella, Ambrosiella and Graphium. A number of these species, i.e. L. fruticetum, Hyalorhinocladiella sp. 2, O. bicolor and O. manitobense, were isolated repeatedly from I. perturbatus, while others, i.e. Graphium sp. 1 and O. piceaperdum, seemed to be␣sporadic associates. Among all the isolates, L. fruticetum had the highest relative dominance in this survey. A high frequency of occurrence of this species with the beetle may indicate a specific relationship between the two partners. 相似文献
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Inhibitory Effect of Hsa‐miR‐590‐5p on Cardiosphere‐derived Stem Cells Differentiation Through Downregulation of TGFB Signaling
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Khorasanizadeh S 《Current opinion in structural biology》2011,21(6):744-749
Histone tails undergo methylation at their lysines and arginines. These chemical marks act as traffic signals that direct activity of chromatin remodeling complexes to appropriate regions of the genome. A surprisingly diverse group of effector protein modules in chromatin remodeling complexes and their associated factors are involved in the recognition of histone methyllysines. Previous studies generally painted a picture of individual lysines recognized by these protein modules in a 1:1 fashion. However, recent structural studies show more complex interactions where the critical lysines are recognized in pairs, or in the context of nucleosomal DNA, or within the central pore of repeat motifs. These interactions extend our understanding of how histone tail recognition can be enhanced through coupled interactions within a single module or through the cooperation of two different molecules. 相似文献
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Structural alignment of proteins is widely used in various fields of structural biology. In order to further improve the quality of alignment, we describe an algorithm for structural alignment based on text modelling techniques. The technique firstly superimposes secondary structure elements of two proteins and then, models the 3D-structure of the protein in a sequence of alphabets. These sequences are utilized by a step-by-step sequence alignment procedure to align two protein structures. A benchmark test was organized on a set of 200 non-homologous proteins to evaluate the program and compare it to state of the art programs, e.g. CE, SAL, TM-align and 3D-BLAST. On average, the results of all-against-all structure comparison by the program have a competitive accuracy with CE and TM-align where the algorithm has a high running speed like 3D-BLAST. 相似文献
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Blus BJ Wiggins K Khorasanizadeh S 《Critical reviews in biochemistry and molecular biology》2011,46(6):507-526
The chromatin organization modifier domain (chromodomain) was first identified as a motif associated with chromatin silencing in Drosophila. There is growing evidence that chromodomains are evolutionary conserved across different eukaryotic species to control diverse aspects of epigenetic regulation. Although originally reported as histone H3 methyllysine readers, the chromodomain functions have now expanded to recognition of other histone and non-histone partners as well as interaction with nucleic acids. Chromodomain binding to a diverse group of targets is mediated by a conserved substructure called the chromobox homology region. This motif can be used to predict methyllysine binding and distinguish chromodomains from related Tudor "Royal" family members. In this review, we discuss and classify various chromodomains according to their context, structure and the mechanism of target recognition. 相似文献