Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.     

产甘油重组大肠杆菌的构建及其耐高渗透压性能的测定

克隆了酿酒酵母(Saccharomyces cerevisiae) 中的3-磷酸甘油脱氢酶和3-磷酸甘油酯酶基因,通过融合PCR构建了双基因共表达载体,将酵母细胞内应答渗透压变化的甘油合成途径引入大肠杆菌（Escherichia coli）。以葡萄糖为底物对重组大肠杆菌进行摇瓶发酵培养,该重组菌的甘油产量为1g/L。渗透压胁迫测试证明该重组菌的耐渗透压性能较出发菌株有明显提高。     

试论汉语语素的类型及其相关概念

科学研究离不开分类 ,本文通过对汉语中最基本的语法单位语素的分类研究 ,不仅准确地定义了汉语虚词 ,而且理清了汉语语法研究中长期混淆不清的两个概念———汉语虚语与附加成分的界限     

Nutrient relationships between Orobanche fasciculata Nutt. and its host Artemisia pygmaea Gray in the Uinta Basin of Utah, USA

Patterns of mineral nutrient uptake and distribution within the roots, stems, and leaves of Artemisia pygmaea and in the vascular parasite Orobanche fasciculata were investigated. All nutrients studied were magnified over concentrations found in the soil into the host and parasite. Nitrogen, phosphorus, potassium, and zinc were magnified along the flow gradient of soil-roots-stems-leaves of the host. All others increased in the roots and then decreased in the stems and leaves. Orobanche fasciculata concentrated phosphorus, potassium, and sodium over soil and root concentrations while excluding to some degree all others.     

Sustainable water resources management: River basin modelling and decision support framework

Sustainability is a key objective of water resources management and this paper describes a modelling and decision support framework that achieves this, illustrated by applications on the UK Thames and Mekong river basins. The decision support framework contains several modules, including an interactive user’s interface linked to a GIS, a geo-database, knowledge base, simulation models and optimization procedures. Based on the analysis of scenarios and proposed interventions, efficient modelling and optimization tools form a comprehensive integrated decision support framework for the analysis and operational management of water resources in the river basin, our emphasis has been on a practical implementation through careful screening of alternatives, consideration of the institutional framework and direct involvement of stakeholders in the decision making process. Operating in this environment is transparent, reproducible and auditable, securing the trust of all interested parties. This paper discusses its applications to water utilisation on the Mekong river basin and drought management of the Lower Thames stored reservoir system.     

The separation of fatty acids

Résumé Le problème de la séparation des acides gras est exposé en détail. Les méthodes physiques couramment appliquées à une macro- ou micro-échelle sont discutées et l'on donne des exemples tirés de la littérature ou de méthodes récemment utilisées dans les recherches. Celles-ci comprennent la cristallisation, la distillation fractionnée, la distribution par contre-courant, la chromatographie en phase gazeuse et la spectrographie de masse.

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Presented before the symposium on Chemistry and Physiology of Fats at the meeting of the Chemical Institute of Canada, Ottawa, October 9, 1957. Hormel Institute publication No. 168.     

TM-Zn金属间化合物结构稳定性的第一性原理研究

基于能带结构,提出Jahn-Teller效应的诱发条件.基于声子色散曲线,揭示晶格动态稳定性和简并振动模式产生劈裂的物理特征.基于电子局域化函数和束缚能,揭示原子成键特性.结果表明,TM-Zn(TM=Ni,Pd,Pt,Cu,Ag,Au)金属间化合物发生立方到四方的相变变形过程中,结构保持稳定.     

Genome sequence of the human malaria parasite Plasmodium falciparum

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.