Indoxyl derivatives of drug metabolites

Summary Indoxyl derivatives were detected as minor products among the urinary metabolites of two trial drugs, a benzodiazepine (GP 55 129) and a benzophenone (CGP 11 952). Their structures were elucidated by NMR and mass spectroscopy. Presumably, metabolites containing potential aldehyde functions react spontaneously with endogenous indoxyl. Such derivatives have not hitherto been encountered in drug metabolism.     

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     

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.     

Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression

Although proteins fulfil most of the requirements that biology has for structural and functional components such as enzymes and receptors, RNA can also serve in these capacities. For example, RNA has sufficient structural plasticity to form ribozyme and receptor elements that exhibit considerable enzymatic power and binding specificity. Moreover, these activities can be combined to create allosteric ribozymes that are modulated by effector molecules. It has also been proposed that certain messenger RNAs might use allosteric mechanisms to mediate regulatory responses depending on specific metabolites. We report here that mRNAs encoding enzymes involved in thiamine (vitamin B(1)) biosynthesis in Escherichia coli can bind thiamine or its pyrophosphate derivative without the need for protein cofactors. The mRNA-effector complex adopts a distinct structure that sequesters the ribosome-binding site and leads to a reduction in gene expression. This metabolite-sensing regulatory system provides an example of a 'riboswitch' whose evolutionary origin might pre-date the emergence of proteins.     

Coenzyme Q is an obligatory cofactor for uncoupling protein function

Uncoupling proteins (UCPs) are thought to be intricately controlled uncouplers that are responsible for the futile dissipation of mitochondrial chemiosmotic gradients, producing heat rather than ATP. They occur in many animal and plant cells and form a subfamily of the mitochondrial carrier family. Physiological uncoupling of oxidative phosphorylation must be strongly regulated to avoid deterioration of the energy supply and cell death, which is caused by toxic uncouplers. However, an H+ transporting uncoupling function is well established only for UCP1 from brown adipose tissue, and the regulation of UCP1 by fatty acids, nucleotides and pH remains controversial. The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies made us seek a native UCP cofactor. Here we report the identification of coenzyme Q (ubiquinone) as such a cofactor. On addition of CoQ10 to reconstituted UCP1 from inclusion bodies, fatty-acid-dependent H+ transport reached the same rate as with native UCP1. The H+ transport was highly sensitive to purine nucleotides, and activated only by oxidized but not reduced CoQ. H+ transport of native UCP1 correlated with the endogenous CoQ content.     

“名词”意义是否宽泛了点？

<中国科技术语>编辑部: 收到你们的<中国科技术语>第一期,非常感谢.读了这期文章,深感不仅是刊物名称的改动,也看到内容的拓宽与提高.     

MYH9 is associated with nondiabetic end-stage renal disease in African Americans

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.     

Indoxyl derivatives of drug metabolites

Indoxyl derivatives were detected as minor products among the urinary metabolites of two trial drugs, a benzodiazepine (GP 55 129) and a benzophenone (CGP 11 952). Their structures were elucidated by NMR and mass spectroscopy. Presumably, metabolites containing potential aldehyde functions react spontaneously with endogenous indoxyl. Such derivatives have not hitherto been encountered in drug metabolism.