Oxysterols direct immune cell migration via EBI2

Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.     

S-nitrosylation of NADPH oxidase regulates cell death in plant immunity

Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection. However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals.     

扎龙湿地土地覆盖变化分析

利用遥感与地理信息系统技术分析1979-2006年间的一系列卫星影像,研究了扎龙湿地土地覆盖的数量变化,速度变化,趋势变化及引起这些变化的水的空间分布的变化．     

基于MEMS的压电厚膜谐振梁能量收集器的研究

在谐振梁能量收集器中PZT膜材料的制备起着至关重要的作用,复合结构的锆钛酸铅(PZT)厚膜采用溶胶-凝胶方法旋涂在硅基的Au/Cr/SiO2/Si结构衬底的制备方法,主要因为溶胶-凝胶制备方法简单,成本低适合于集成制作.改进PZT组分和和0-3混合法及复合结构的Au/Cr/SiO2/Si衬底,使制备的PZT厚膜避免了厚...     

三亚景区游客游憩动机初探

运用因子分析方法研究了三亚景区游客的游憩动机,确立了社会交往与身体享受、逃避日常环境、增长见识、心灵享受四个动机因子,进一步运用聚类分析方法将游客分为求知型、逃避型、社交与享受型三个类别,在此基础上分析了三种不同游憩动机旅游者在人口统计特征及游憩行为上的差异.结果显示:三类旅游者在性别、年龄、受教育程度上等社会人口特征上都无显著差异,仅在人均月收入方面差异显著,收入者较高者出游多出于社交原因或者身体享受的动机,而低收入者的动机多为增长知识.     

一类恒化器模型解的稳定性

讨论一类含1个食饵和1个捕食者种群的恒化器模型的整体解.分析该模型解的一致有界性,运用线性化方法和Lyapunov函数方法研究该模型非负平衡点的局部渐近稳定性和全局渐近稳定性.     

我国化学化工领域毕业生及学位授予情况的调研与分析

本文基于对我国化学化工领域2006-2010年间本科生、硕士研究生和博士研究生培养情况的调研数据,分析了不同学位层次毕业生数量变化趋势、毕业生在各学科门类及培养单位的分布情况,进而讨论了我国化学化工领域学生培养的结构特点及人才队伍趋势.     

神经电活动稳态调控抑制性突触传递的分子机制

发育中的神经网络需要兼顾生长与稳定这两种相辅相成的需求.稳态可塑性可通过调节兴奋性或抑制性突触传递从而维持神经网络的稳定.已报道的关于稳态可塑性机制方面的研究主要集中在其对兴奋性突触传递的影响,很少关注其对抑制性突触的调控.运用体外培养的原代海马神经元,本项研究发现了持续增强神经元电活动4小时能够诱导抑制性突触传递的稳...     

High-frequency, scaled graphene transistors on diamond-like carbon

Owing to its high carrier mobility and saturation velocity, graphene has attracted enormous attention in recent years. In particular, high-performance graphene transistors for radio-frequency (r.f.) applications are of great interest. Synthesis of large-scale graphene sheets of high quality and at low cost has been demonstrated using chemical vapour deposition (CVD) methods. However, very few studies have been performed on the scaling behaviour of transistors made from CVD graphene for r.f. applications, which hold great potential for commercialization. Here we report the systematic study of top-gated CVD-graphene r.f. transistors with gate lengths scaled down to 40 nm, the shortest gate length demonstrated on graphene r.f. devices. The CVD graphene was grown on copper film and transferred to a wafer of diamond-like carbon. Cut-off frequencies as high as 155 GHz have been obtained for the 40-nm transistors, and the cut-off frequency was found to scale as 1/(gate length). Furthermore, we studied graphene r.f. transistors at cryogenic temperatures. Unlike conventional semiconductor devices where low-temperature performance is hampered by carrier freeze-out effects, the r.f. performance of our graphene devices exhibits little temperature dependence down to 4.3 K, providing a much larger operation window than is available for conventional devices.     

Overcoming lability of extremely long alkane carbon-carbon bonds through dispersion forces

Steric effects in chemistry are a consequence of the space required to accommodate the atoms and groups within a molecule, and are often thought to be dominated by repulsive forces arising from overlapping electron densities (Pauli repulsion). An appreciation of attractive interactions such as van der Waals forces (which include London dispersion forces) is necessary to understand chemical bonding and reactivity fully. This is evident from, for example, the strongly debated origin of the higher stability of branched alkanes relative to linear alkanes and the possibility of constructing hydrocarbons with extraordinarily long C-C single bonds through steric crowding. Although empirical bond distance/bond strength relationships have been established for C-C bonds (longer C-C bonds have smaller bond dissociation energies), these have no present theoretical basis. Nevertheless, these empirical considerations are fundamental to structural and energetic evaluations in chemistry, as summarized by Pauling as early as 1960 and confirmed more recently. Here we report the preparation of hydrocarbons with extremely long C-C bonds (up to 1.704??), the longest such bonds observed so far in alkanes. The prepared compounds are unexpectedly stable--noticeable decomposition occurs only above 200?°C. We prepared the alkanes by coupling nanometre-sized, diamond-like, highly rigid structures known as diamondoids. The extraordinary stability of the coupling products is due to overall attractive dispersion interactions between the intramolecular H???H contact surfaces, as is evident from density functional theory computations with and without inclusion of dispersion corrections.