Potentiative effects of sulfhydryl compounds on carrageenin-induced oedema in rats and relationship to their potencies as inhibitors of angiostin-converting enzyme in vivo

Summary Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo.Acknowledgment. The authors wish to thank Prof. H. Fujimura, Department of Pharmacology, Gifu University School of Medicine, for his helpful advice.     

Global variation in copy number in the human genome

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.     

Evidence from fluid inclusions for microbial methanogenesis in the early Archaean era

Methanogenic microbes may be one of the most primitive organisms, although it is uncertain when methanogens first appeared on Earth. During the Archaean era (before 2.5 Gyr ago), methanogens may have been important in regulating climate, because they could have provided sufficient amounts of the greenhouse gas methane to mitigate a severely frozen condition that could have resulted from lower solar luminosity during these times. Nevertheless, no direct geological evidence has hitherto been available in support of the existence of methanogens in the Archaean period, although circumstantial evidence is available in the form of approximately 2.8-Gyr-old carbon-isotope-depleted kerogen. Here we report crushing extraction and carbon isotope analysis of methane-bearing fluid inclusions in approximately 3.5-Gyr-old hydrothermal precipitates from Pilbara craton, Australia. Our results indicate that the extracted fluids contain microbial methane with carbon isotopic compositions of less than -56 per thousand included within original precipitates. This provides the oldest evidence of methanogen (> 3.46 Gyr ago), pre-dating previous geochemical evidence by about 700 million years.     

高温循环变形对JLF-1钢微观结构的影响

低活性铁素体/马氏体钢,JLF-1,是聚变堆和超临界水冷堆的候选结构材料,高温循环软化现象是设计必须考虑的因素之一.为掌握JLF-1钢高温循环变形机理,本文采用透射电镜对JLF-1钢高温低周疲劳后样品的微观结构进行了分析,发现JLF-1钢的循环软化现象与位错密度、位错胞、板条宽度有关 其峰值拉应力与位错密度、板条宽度呈函数关系.     

A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy.

Malattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD) refer to two autosomal dominant diseases characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium (RPE). Both loci were mapped to chromosome 2p16-21 (refs 5,6) and this genetic interval has been subsequently narrowed. The importance of these diseases is due in large part to their close phenotypic similarity to age-related macular degeneration (AMD), a disorder with a strong genetic component that accounts for approximately 50% of registered blindness in the Western world. Just as in ML and DHRD, the early hallmark of AMD is the presence of drusen. Here we use a combination of positional and candidate gene methods to identify a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for EGF-containing fibrillin-like extracellular matrix protein 1) in all families studied. This change was not present in 477 control individuals or in 494 patients with age-related macular degeneration. Identification of this mutation may aid in the development of an animal model for drusen, as well as in the identification of other genes involved in human macular degeneration.     

Effect of lipophilic cations on thiamine transport system in isolated rat hepatocytes

The effect of lipophilic cations such as triphenylmethylphosphonium, tetraphenylphosphonium and tetraphenylarsonium in addition to dibenzyldimethylammonium on thiamine transport in isolated rat hepatocytes was studied. Lipophilic cations at the concentration 10 microM almost completely inhibited thiamine uptake. Kinetic studies showed that these compounds were competitive inhibitors with a very high affinity. These results suggest that lipophilic cations in addition to quaternary ammonium compounds also share a common binding site for thiamine in isolated rat hepatocytes.     

Choline accumulation in isolated rat hepatocytes

Summary The accumulation of non-metabolized choline in isolated rat hepatocytes is concentrative in Na⁺ medium, whereas the accumulation does not exceed unity in a Li⁺ medium. Ouabain and 2,4-dinitrophenol inhibited the choline uptake. These results indicate that choline is taken up by rat hepatocytes via a Na⁺-and energy-dependent process, and choline oxidase is not directly connected with the choline transport system.     

提高层次分析法评价精度的几种方法

为了提高层次分析法在实际应用中的评价精度，本文拟从调查表、标度的选择、判断矩阵的建立、以及“序位逆转”问题的正确认识等几个关键阶段进行了分析和研究，并提出了相应的改进思路及处理方法。由此可为理论与实际工作者正确应用层次分析法、提高其评价准确性及可信度提供一个有效、实用的参考方法。