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Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer 总被引:26,自引:0,他引:26
Tomlinson IP Alam NA Rowan AJ Barclay E Jaeger EE Kelsell D Leigh I Gorman P Lamlum H Rahman S Roylance RR Olpin S Bevan S Barker K Hearle N Houlston RS Kiuru M Lehtonen R Karhu A Vilkki S Laiho P Eklund C Vierimaa O Aittomäki K Hietala M Sistonen P Paetau A Salovaara R Herva R Launonen V Aaltonen LA;Multiple Leiomyoma Consortium 《Nature genetics》2002,30(4):406-410
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During the past decade it has been shown conclusively that the incineration of municipal and industrial wastes gives rise to emissions of chlorinated dibenzodioxins and dibenzofurans. However, the mechanism by which these toxic compounds are formed has not yet been fully established. Some researchers believe that the presence of organically bound chlorine is necessary, but others consider that inorganic forms of chlorine may also participate in the process. We now report the synthesis of a large number of chlorinated environmental pollutants in a simple high-temperature experiment. The results show that phenol and HCl are the most likely precursors of the chlorinated dibenzodioxins and dibenzofurans formed in the combustion of wastes. The dependence of the reaction on the concentration of HCl indicates a way of controlling the formation of these toxic compounds during incineration. 相似文献
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Three-dimensional structure of the free radical protein of ribonucleotide reductase 总被引:23,自引:0,他引:23
The enzyme ribonucleotide reductase furnishes precursors for the DNA synthesis of all living cells. One of its constituents, the free radical protein, has an unusual alpha-helical structure. There are two iron centres that are about 25 A apart in the dimeric molecule. Tyrosine 122, which harbours the stable free radical necessary for the activity of ribonucleotide reductase, is buried inside the protein and is located 5 A from the closest iron atom. 相似文献
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In this report we describe the main features of the initially determined alcohol dehydrogenase, that of horse liver, relate
this to the human enzyme structures and review recent structural studies on mutants and new complexes of the enzymes. We further
review the structure of a bacterial alcohol dehydrogenase to arrive at a coherent picture of medium-chain dehydrogenase/reductase
alcohol dehydrogenases in general. 相似文献
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Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein after induction of airway inflammation in asthmatics 总被引:13,自引:0,他引:13
Lensmar C Nord M Gudmundsson GH Roquet A Andersson O Jörnvall H Eklund A Grunewald J Agerberth B 《Cellular and molecular life sciences : CMLS》2000,57(6):976-981
The Clara cell 16 kDa protein (CC16) maps to an atopy-associated region of chromosome 11 and has been ascribed an anti-inflammatory
function. Using reverse-phase HPLC and Western blot analysis, we have evaluated the polypeptide pattern in bronchoalveolar
lavage (BAL) fluid retrieved from asthmatics, before and after induction of airway inflammation by low-dose allergen inhalation
challenge. A prominent decrease of CC16 was seen after induction of inflammation, and a further CC16 decrease was observed
in lavage fluid where surfactant had been removed. Reduced levels of pulmonary CC16 may cause loss of anti-inflammatory activity
in the airways and contribute to the development of airway inflammation in asthma.
Received 22 March 2000; received after revision 4 May 2000; accepted 4 May 2000 相似文献
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A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers 总被引:2,自引:0,他引:2
We developed a computational method to characterize aneuploidy in tumor samples based on coordinated aberrations in expression of genes localized to each chromosomal region. We summarized the total level of chromosomal aberration in a given tumor in a univariate measure termed total functional aneuploidy. We identified a signature of chromosomal instability from specific genes whose expression was consistently correlated with total functional aneuploidy in several cancer types. Net overexpression of this signature was predictive of poor clinical outcome in 12 cancer data sets representing six cancer types. Also, the signature of chromosomal instability was higher in metastasis samples than in primary tumors and was able to stratify grade 1 and grade 2 breast tumors according to clinical outcome. These results provide a means to assess the potential role of chromosomal instability in determining malignant potential over a broad range of tumors. 相似文献
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Oxygen-evolving photosynthetic organisms regulate carbon metabolism through a light-dependent redox signalling pathway. Electrons are shuttled from photosystem I by means of ferredoxin (Fdx) to ferredoxin-thioredoxin reductase (FTR), which catalyses the two-electron-reduction of chloroplast thioredoxins (Trxs). These modify target enzyme activities by reduction, regulating carbon flow. FTR is unique in its use of a [4Fe-4S] cluster and a proximal disulphide bridge in the conversion of a light signal into a thiol signal. We determined the structures of FTR in both its one- and its two-electron-reduced intermediate states and of four complexes in the pathway, including the ternary Fdx-FTR-Trx complex. Here we show that, in the first complex (Fdx-FTR) of the pathway, the Fdx [2Fe-2S] cluster is positioned suitably for electron transfer to the FTR [4Fe-4S] centre. After the transfer of one electron, an intermediate is formed in which one sulphur atom of the FTR active site is free to attack a disulphide bridge in Trx and the other sulphur atom forms a fifth ligand for an iron atom in the FTR [4Fe-4S] centre--a unique structure in biology. Fdx then delivers a second electron that cleaves the FTR-Trx heterodisulphide bond, which occurs in the Fdx-FTR-Trx complex. In this structure, the redox centres of the three proteins are aligned to maximize the efficiency of electron transfer from the Fdx [2Fe-2S] cluster to the active-site disulphide of Trxs. These results provide a structural framework for understanding the mechanism of disulphide reduction by an iron-sulphur enzyme and describe previously unknown interaction networks for both Fdx and Trx (refs 4-6). 相似文献
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