Structure of the detoxification catalyst mercuric ion reductase from Bacillus sp. strain RC607

Several hundred million tons of toxic mercurials are dispersed in the biosphere. Microbes can detoxify organo-mercurials and mercury salts through sequential action of two enzymes, organomercury lyase and mercuric ion reductase (MerA). The latter, a homodimer with homology to the FAD-dependent disulphide oxidoreductases, catalyses the reaction NADPH + Hg(II)----NADP+ + H+ + Hg(0), one of the very rare enzymic reactions with metal substrates. Human glutathione reductase serves as a reference molecule for FAD-dependent disulphide reductases and between its primary structure and that of MerA from Tn501 (Pseudomonas), Tn21 (Shigella), p1258 (Staphylococcus) and Bacillus, 25-30% of the residues have been conserved. All MerAs have a C-terminal extension about 15 residues long but have very varied N termini. Although the enzyme from Streptomyces lividans has no addition, from Pseudomonas aeruginosa Tn501 and Bacillus sp. strain RC607 it has one and two copies respectively of a domain of 80-85 residues, highly homologous to MerP, the periplasmic component of proteins encoded by the mer operon. These domains can be proteolytically cleaved off without changing the catalytic efficiency. We report here the crystal structure of MerA from the Gram-positive bacterium Bacillus sp. strain RC607. Analysis of its complexes with nicotinamide dinucleotide substrates and the inhibitor Cd(II) reveals how limited structural changes enable an enzyme to accept as substrate what used to be a dangerous inhibitor. Knowledge of the mode of mercury ligation is a prerequisite for understanding this unique detoxification mechanism.     

一种适合于网络专家系统的通用理论(英文)

描述运用于工业自动化的一种自适应自学习方法。基于此方法,Ａｐｔｒｏｎｉｘ公司开发出一套通用软件工具－ＳＴＩＭＴＭ,并应用于不同工业领域。ＳＴＩＭ可用于构造各类专家系统。基于因素空间理论,ＳＴＩＭ具有一系列独特之处,比如自动化、自学习,以及自翻译。如果与因特网,嵌入式控制器以及可编程逻辑控制器等结合使用,ＳＴＩＭ则成为一个十分有效的工具,可应用于远程连通与控制、模式识别、机器故障诊断,以及自动化加工过程中的传感器数据融合     

0957 + 561 A, B: twin quasistellar objects or gravitational lens?

0957 + 561 A, B are two QSOs of mag 17 with 5.7 arc s separation at redshift 1.405. Their spectra leave little doubt that they are associated. Difficulties arise in describing them as two distinct objects and the possibility that they are two images of the same object formed by a gravitational lens is discussed.     

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome

Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors.     

Lessons from natural molecules

Natural products have inspired chemists and physicians for millennia. Their rich structural diversity and complexity has prompted synthetic chemists to produce them in the laboratory, often with therapeutic applications in mind, and many drugs used today are natural products or natural-product derivatives. Recent years have seen considerable advances in our understanding of natural-product biosynthesis. Coupled with improvements in approaches for natural-product isolation, characterization and synthesis, these could be opening the door to a new era in the investigation of natural products in academia and industry.     

克拉2气田石油地质特征

克拉2气田位于库车拗陷克拉苏构造带中段, 是双重构造中呈串珠状分布的一系列褶皱中的一个局部构造. 含气层系以下白垩统巴什基奇克组砂岩为主, 其次为下第三系库姆格列木群白云岩段和砂砾岩段及下白垩统巴西盖组砂岩. 天然气中甲烷含量大于97%, 属于干气, 气源为侏罗系煤系地层. 克拉2号构造圈闭形成于西域期, 成藏期晚. 下第三系厚层膏盐区域盖层形成的良好封盖条件及其成藏期晚是克拉2大气田得以很好保存的根本原因. 克拉2气田的异常高压是由于西域期来自北部的强烈构造挤压作用而形成的.     

Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification

The genetic analysis of congenital skull malformations provides insight into normal mechanisms of calvarial osteogenesis. Enlarged parietal foramina (PFM) are oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM are usually asymptomatic, but may be associated with headache, scalp defects and structural or vascular malformations of the brain. Inheritance is frequently autosomal dominant, but no causative mutations have been identified in non-syndromic cases. We describe here heterozygous mutations of the homeobox gene MSX2 (located on 5q34-q35) in three unrelated families with PFM. One is a deletion of approximately 206 kb including the entire gene and the others are intragenic mutations of the DNA-binding homeodomain (RK159-160del and R172H) that predict disruption of critical intramolecular and DNA contacts. Mouse Msx2 protein with either of the homeodomain mutations exhibited more than 85% reduction in binding to an optimal Msx2 DNA-binding site. Our findings contrast with the only described MSX2 homeodomain mutation (P148H), associated with craniosynostosis, that binds with enhanced affinity to the same target. This demonstrates that MSX2 dosage is critical for human skull development and suggests that PFM and craniosynostosis result, respectively, from loss and gain of activity in an MSX2-mediated pathway of calvarial osteogenic differentiation.