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21.
本文通过Aβ25-35诱导体外原代培养的SD乳大鼠海马神经元,建立Aβ毒性损伤细胞模型,结合AnnexinV-FITC/PI荧光双染法流式细胞术、MTT比色法、实时荧光定量PCR及Western blot方法检测川芎嗪(tetrameth-ylpyrazine,TMP)对原代培养的海马神经元细胞活性、早期凋亡率和Bax、Bcl-2基因表达的影响。结果显示川芎嗪高、中剂量可明显增强细胞活性,增加神经元细胞的存活率(P<0.01),可显著抑制海马神经元细胞早期凋亡(P<0.01),抑制凋亡蛋白Bax的表达(P<0.01),增强抗凋亡蛋白bcl-2的表达(P<0.01)。川芎嗪可通过调节Bax/Bcl-2平衡抵抗Aβ25-35诱导的海马神经元凋亡,降低Aβ的神经元毒性,对海马神经元损伤有明显的保护作用。 相似文献
22.
水淹状况是湿地植被动态的重要影响因素。该研究基于谷歌地球引擎(GEE)平台, 利用2000-03-01至2020-02-29所有覆盖研究区域的MODIS遥感影像数据, 分析20年间水淹频率(IF)、增强型植被指数(EVI)的时空变化以及湿地植被对IF变化的响应, 得出以下结论: (1) 20年来鄱阳湖水文节律发生了明显改变, 高IF (IF > 75%)水域面积呈现下降趋势, 从2000年1 435.3 km2下降至2019年的510.25 km2, 降幅为64.45%; (2)区域平均EVI呈显著上升趋势, 植被扩张主要集中在中部IF下降区域; (3)分析不同总水淹频率区域中平均EVI年际变化, 发现EVI与水淹状况的变化趋势相似, 2009年之后鄱阳湖水域面积萎缩趋势缓解, EVI增长速度出现下降; (4)鄱阳湖湿地植被主要沿水域面积萎缩方向扩张, 基于像元统计20年间IF与EVI的变化趋势, 发现它们在空间分布上高度吻合, 这种空间异质性进一步证实水淹状况起到调节植被动态变化的作用。 相似文献
23.
Andrews PD Ovechkina Y Morrice N Wagenbach M Duncan K Wordeman L Swedlow JR 《Developmental cell》2004,6(2):253-268
Chromosome orientation and alignment within the mitotic spindle requires the Aurora B protein kinase and the mitotic centromere-associated kinesin (MCAK). Here, we report the regulation of MCAK by Aurora B. Aurora B inhibited MCAK's microtubule depolymerizing activity in vitro, and phospho-mimic (S/E) mutants of MCAK inhibited depolymerization in vivo. Expression of either MCAK (S/E) or MCAK (S/A) mutants increased the frequency of syntelic microtubule-kinetochore attachments and mono-oriented chromosomes. MCAK phosphorylation also regulates MCAK localization: the MCAK (S/E) mutant frequently localized to the inner centromere while the (S/A) mutant concentrated at kinetochores. We also detected two different binding sites for MCAK using FRAP analysis of the different MCAK mutants. Moreover, disruption of Aurora B function by expression of a kinase-dead mutant or RNAi prevented centromeric targeting of MCAK. These results link Aurora B activity to MCAK function, with Aurora B regulating MCAK's activity and its localization at the centromere and kinetochore. 相似文献
24.
Lizcano JM Deak M Morrice N Kieloch A Hastie CJ Dong L Schutkowski M Reimer U Alessi DR 《The Journal of biological chemistry》2002,277(31):27839-27849
25.
Inositol acylation is an obligatory step in glycosylphosphatidylinositol (GPI) biosynthesis whereas mature GPI anchors often lack this modification. The GPI anchors of Trypanosoma brucei variant surface glycoproteins (VSGs) undergo rounds of inositol acylation and deacylation during GPI biosynthesis and the deacylation reactions are inhibited by diisopropylfluorophosphate (DFP). Inositol deacylase was affinity labelled with [3H]DFP and purified. Peptide sequencing was used to clone GPIdeAc, which encodes a protein with significant sequence and hydropathy similarity to mammalian acyloxyacyl hydrolase, an enzyme that removes fatty acids from bacterial lipopolysaccharide. Both contain a signal sequence followed by a saposin domain and a GDSL-lipase domain. GPIdeAc(-/-) trypanosomes were viable in vitro and in animals. Affinity-purified HA-tagged GPIdeAc was shown to have inositol deacylase activity. However, total inositol deacylase activity was only reduced in GPIdeAc(-/-) trypanosomes and the VSG GPI anchor was indistinguishable from wild type. These results suggest that there is redundancy in T.brucei inositol deacylase activity and that there is another enzyme whose sequence is not recognizably related to GPIdeAc. 相似文献
26.
Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway 总被引:7,自引:0,他引:7
Seternes OM Mikalsen T Johansen B Michaelsen E Armstrong CG Morrice NA Turgeon B Meloche S Moens U Keyse SM 《The EMBO journal》2004,23(24):4780-4791
Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK), which is regulated by protein stability. However, its function is unknown and no physiological substrates for ERK3 have yet been identified. Here we demonstrate a specific interaction between ERK3 and MAPK-activated protein kinase-5 (MK5). Binding results in nuclear exclusion of both ERK3 and MK5 and is accompanied by ERK3-dependent phosphorylation and activation of MK5 in vitro and in vivo. Endogenous MK5 activity is significantly reduced by siRNA-mediated knockdown of ERK3 and also in fibroblasts derived from ERK3-/- mice. Furthermore, increased levels of ERK3 protein detected during nerve growth factor-induced differentiation of PC12 cells are accompanied by an increase in MK5 activity. Conversely, MK5 depletion causes a dramatic reduction in endogenous ERK3 levels. Our data identify the first physiological protein substrate for ERK3 and suggest a functional link between these kinases in which MK5 is a downstream target of ERK3, while MK5 acts as a chaperone for ERK3. Our findings provide valuable tools to further dissect the regulation and biological roles of both ERK3 and MK5. 相似文献
27.
JF Yuan SJ Zhang O Jafer RA Furlong OE Chausiaux CA Sargent GH Zhang NA Affara 《BMC microbiology》2009,9(1):246
Background
Pseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult. 相似文献28.
29.
Soil inorganic carbon storage pattern in China 总被引:1,自引:0,他引:1
NA MI SHAOQIANG WANG JIYUAN LIU GUIRUI YU WENJUAN ZHANG ESTEBAN JOBBÁGY 《Global Change Biology》2008,14(10):2380-2387
Soils with pedogenic carbonate cover about 30% (3.44 × 106 km2) of China, mainly across its arid and semiarid regions in the Northwest. Based on the second national soil survey (1979–1992), total soil inorganic carbon (SIC) storage in China was estimated to be 53.3±6.3 PgC (1 Pg=1015 g) to the depth investigated to 2 m. Soil inorganic carbon storages were 4.6, 10.6, 11.1, and 20.8 Pg for the depth ranges of 0–0.1, 0.1–0.3, 0.3–0.5, and 0.5–1 m, respectively. Stocks for 0.1, 0.3, 0.5, and 1 m of depth accounted for 8.7%, 28.7%, 49.6%, and 88.9% of total SIC, respectively. In contrast with soil organic carbon (SOC) storage, which is highest under 500–800 mm yr−1 of mean precipitation, SIC storage peaks where mean precipitation is <400 mm yr−1. The amount and vertical distribution of SIC was related to climate and land cover type. Content of SIC in each incremental horizon was positively related with mean annual temperature and negatively related with mean annual precipitation, with the magnitude of SIC content across land cover types showing the following order: desert, grassland >shrubland, cropland >marsh, forest, meadow. Densities of SIC increased generally with depth in all ecosystem types with the exception of deserts and marshes where it peaked in intermediate layers (0.1–0.3 m for first and 0.3–0.5 m for latter). Being an abundant component of soil carbon stocks in China, SIC dynamics and the process involved in its accumulation or loss from soils require a better understanding. 相似文献
30.
Douglas P Cui X Block WD Yu Y Gupta S Ding Q Ye R Morrice N Lees-Miller SP Meek K 《Molecular and cellular biology》2007,27(5):1581-1591
The protein kinase activity of the DNA-dependent protein kinase (DNA-PK) is required for the repair of DNA double-strand breaks (DSBs) via the process of nonhomologous end joining (NHEJ). However, to date, the only target shown to be functionally relevant for the enzymatic role of DNA-PK in NHEJ is the large catalytic subunit DNA-PKcs itself. In vitro, autophosphorylation of DNA-PKcs induces kinase inactivation and dissociation of DNA-PKcs from the DNA end-binding component Ku70/Ku80. Phosphorylation within the two previously identified clusters of phosphorylation sites does not mediate inactivation of the assembled complex and only partially regulates kinase disassembly, suggesting that additional autophosphorylation sites may be important for DNA-PK function. Here, we show that DNA-PKcs contains a highly conserved amino acid (threonine 3950) in a region similar to the activation loop or t-loop found in the protein kinase domain of members of the typical eukaryotic protein kinase family. We demonstrate that threonine 3950 is an in vitro autophosphorylation site and that this residue, as well as other previously identified sites in the ABCDE cluster, is phosphorylated in vivo in irradiated cells. Moreover, we show that mutation of threonine 3950 to the phosphomimic aspartic acid abrogates V(D)J recombination and leads to radiation sensitivity. Together, these data suggest that threonine 3950 is a functionally important, DNA damage-inducible phosphorylation site and that phosphorylation of this site regulates the activity of DNA-PKcs. 相似文献