Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis

With more than 55,000 members identified so far in all forms of life, the family of terpene or terpenoid natural products represents the epitome of molecular biodiversity. A well-known and important member of this family is the polycyclic diterpenoid Taxol (paclitaxel), which promotes tubulin polymerization and shows remarkable efficacy in cancer chemotherapy. The first committed step of Taxol biosynthesis in the Pacific yew (Taxus brevifolia) is the cyclization of the linear isoprenoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5),11(12)diene, which is catalysed by taxadiene synthase. The full-length form of this diterpene cyclase contains 862 residues, but a roughly 80-residue amino-terminal transit sequence is cleaved on maturation in plastids. We now report the X-ray crystal structure of a truncation variant lacking the transit sequence and an additional 27 residues at the N terminus, hereafter designated TXS. Specifically, we have determined structures of TXS complexed with 13-aza-13,14-dihydrocopalyl diphosphate (1.82?? resolution) and 2-fluorogeranylgeranyl diphosphate (2.25?? resolution). The TXS structure reveals a modular assembly of three α-helical domains. The carboxy-terminal catalytic domain is a class?I terpenoid cyclase, which binds and activates substrate GGPP with a three-metal ion cluster. The N-terminal domain and a third 'insertion' domain together adopt the fold of a vestigial class?II terpenoid cyclase. A class?II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis.     

Link between spin fluctuations and electron pairing in copper oxide superconductors

Although it is generally accepted that superconductivity is unconventional in the high-transition-temperature copper oxides, the relative importance of phenomena such as spin and charge (stripe) order, superconductivity fluctuations, proximity to a Mott insulator, a pseudogap phase and quantum criticality are still a matter of debate. In electron-doped copper oxides, the absence of an anomalous pseudogap phase in the underdoped region of the phase diagram and weaker electron correlations suggest that Mott physics and other unidentified competing orders are less relevant and that antiferromagnetic spin fluctuations are the dominant feature. Here we report a study of magnetotransport in thin films of the electron-doped copper oxide La(2?-?x)Ce(x)CuO(4). We show that a scattering rate that is linearly dependent on temperature--a key feature of the anomalous normal state properties of the copper oxides--is correlated with the electron pairing. We also show that an envelope of such scattering surrounds the superconducting phase, surviving to zero temperature when superconductivity is suppressed by magnetic fields. Comparison with similar behaviour found in organic superconductors strongly suggests that the linear dependence on temperature of the resistivity in the electron-doped copper oxides is caused by spin-fluctuation scattering.     

In vivo genome editing restores haemostasis in a mouse model of haemophilia

Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation. In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus, but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.     

通过调整势垒高度改善有机电致白光器件的性能

通过利用ADN发光材料和其他各有机发光材料之间的能级关系设计了利用BCP作为空穴阻挡层,Alp3:DCJTB层和Alp3:DCJTB层之间的ADN层为发光层的三种结构的器件.实验结果表明,在NPB层和Alq3:DCJTB层之间不插入ADN,只在Alq3:DCJTB层和BCP层之间插入ADN的器件A的性能最好.其原因在于利用了NPB和发光层之间的LUMO能级较高的势垒限制了电子的迁移和输运,改善了激子的形成几率,促进了白光的形成.该器件的启亮电压为5V,当外加电压达到17V时,器件最大发光亮度达12450 cd/m2.最大效率是1.733 cd/A.     

完全支持数据更新的XML压缩编码

为了有效地更新和查询XML数据,提出了一种新的XML编码方案-分数路径编码(简写为FAPE).FAPE充分利用在两个分数间可以插入无穷多个分数这一特点,支持XML结点数据的无限更新,同时FAPE将结点的相关信息保存在相应的表中,避免记录重复的信息.实验表明:FAPE节省了存储空间,提高了查询效率,更新所花的时间更少.     

抗蛔虫人源单链抗体库的构建及鉴定

目的:构建抗蛔虫人源单链抗体库,从中筛选建抗蛔虫人源特异性单链抗体.方法:分离10个患蛔虫病人的淋巴细胞,提取总RNA反转录为cDNA,PCR扩增人抗体重链(VH)和轻链(VL)可变区基因,采用SOE-PCR法将VH和VL片段随机拼接成scFv片段,并克隆入噬菌粒载体pCANTAB5E中,构建噬菌体单链抗体库.结果:初...     

一类灰色随机多准则群决策方法

针对准则值为区间灰数概率的离散型灰色随机变量且准则权重和决策者权重都完全未知的灰色随机多准则群决策问题,提出了一种基于偏差函数的决策方法.该方法通过计算每个决策者的主观判断矩阵与客观判断矩阵之间的偏差来确定该决策者的权重,基于主客观判断矩阵偏差最小化思想建立规划模型,求解该规划模型可同时得出准则权重向量和决策者权重向量...     

可约矩阵特征值的扰动

主要研究可约矩阵特征值的扰动.对于可约矩阵,给出了Bauer-Fike型的一些结果,这些结果推广了文献[3-5]中相应的结果.     

海口市优势水产品重点养殖区病害调查及分析

2007-2009年,对演丰、三江、灵山、大致坡、红旗、长流、西秀、府城等重点养殖区的罗非鱼(Tilapia sp.)、对虾(Penaeus sp.)养殖水体进行现场调查和分析研究,初步摸清了近3年病害的种类、流行、发病特点及造成的损失情况.细菌性、病毒性疾病是罗非鱼、对虾的主要病害,特别是白斑病、红体病、链球菌病、底死症、高温综合症等发病非常普遍.7-9月份为罗非鱼发病高峰期;3-5月份和9-11月份为对虾发病高峰期.多数病害在调查区域均有分布,发病后死亡率较高.2007-2009年海口市水产病害死亡造成的直接经济损失近281万元.     

日本东北大地震——大自然给人类上的又一课

作者介绍了2011年3月11日日本东北地区太平洋沿岸近海的M9.0特大地震的震后研究情况,日本列岛M8.0以上大地震发生的地球动力学背景、地理环境,大地震在东北太平洋沿岸地区、关东地区、东海道地区的活动历史以及对下一次东海地震发生时间的最新研究进展。最后总结了地震中长期预测的现状及相关基础研究应努力的方向,提出了在工程应用研究中应该避免的错误工作思路。