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951.
Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. 总被引:11,自引:0,他引:11
Michael G Anderson Richard S Smith Norman L Hawes Adriana Zabaleta Bo Chang Janey L Wiggs Simon W M John 《Nature genetics》2002,30(1):81-85
Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (GpnmbR150X) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to GpnmbR150X; otherwise, similar D2 mice that are not homozygous for GpnmbR150X do not develop IPD. ISA is caused by the recessive Tyrp1b mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma. 相似文献
952.
The extent of linkage disequilibrium in Arabidopsis thaliana. 总被引:20,自引:0,他引:20
Magnus Nordborg Justin O Borevitz Joy Bergelson Charles C Berry Joanne Chory Jenny Hagenblad Martin Kreitman Julin N Maloof Tina Noyes Peter J Oefner Eli A Stahl Detlef Weigel 《Nature genetics》2002,30(2):190-193
Linkage disequilibrium (LD), the nonrandom occurrence of alleles in haplotypes, has long been of interest to population geneticists. Recently, the rapidly increasing availability of genomic polymorphism data has fueled interest in LD as a tool for fine-scale mapping, in particular for human disease loci. The chromosomal extent of LD is crucial in this context, because it determines how dense a map must be for associations to be detected and, conversely, limits how finely loci may be mapped. Arabidopsis thaliana is expected to harbor unusually extensive LD because of its high degree of selfing. Several polymorphism studies have found very strong LD within individual loci, but also evidence of some recombination. Here we investigate the pattern of LD on a genomic scale and show that in global samples, LD decays within approximately 1 cM, or 250 kb. We also show that LD in local populations may be much stronger than that of global populations, presumably as a result of founder events. The combination of a relatively high level of polymorphism and extensive haplotype structure bodes well for developing a genome-wide LD map in A. thaliana. 相似文献
953.
早-中元古代Columbia超级大陆研究进展 总被引:17,自引:1,他引:17
地球在过去25亿年里曾发生过几次全球性大规模碰撞造山事件(如 Grenville事件,Pan-African事件等);地质学家由此推测大陆块自早元古代以来曾发生过周期性拼合和分离,从而导致古超级大陆的形成和裂解[1].在过去10年里(1991~2001年),被认为由约1.0 Ga Grenville造山事件所形成的超级大陆Rodinia已成为古大陆重建的一个热点[2,3].然而,地质学家们在重建Rodinia 过程中发现,并非全部Rodinia组成陆块都是由Grenville造山带所焊接,而 相似文献
954.
首先介绍了判断控制的两种标准:定量标准与定性标准,然后通过分析使用定量标准确定合并范围的不足,得出合并范围的确定庆以定性标准为主,定量标准为辅的结论。并构造了流程图来说明两种标准的具体应用。 相似文献
955.
青藏高原北羌塘新生代火山岩黑云母地球化学及其岩石学意义 总被引:3,自引:0,他引:3
分析了北羌塘半岛湖新第三纪玻基粗面安山岩中黑云母的常量、微量及稀土元素特征.结果表明,黑云母均属钛铁黑云母类,富集大离子亲石元素Ba以及Sc,Ti,V,Cr,Co,Ni等铁族元素,而相对亏损Th,U,Pb等亲石元素.轻稀土强烈富集,轻重稀土分异显著,但Eu亏损并不严重,暗示原始岩浆来源于一个基性岩质的、相当于榴辉岩矿物相(斜长石相缺失)的源区类型. 相似文献
956.
Superoxide activates mitochondrial uncoupling proteins. 总被引:64,自引:0,他引:64
Karim S Echtay Damien Roussel Julie St-Pierre Mika B Jekabsons Susana Cadenas Jeff A Stuart James A Harper Stephen J Roebuck Alastair Morrison Susan Pickering John C Clapham Martin D Brand 《Nature》2002,415(6867):96-99
Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria. 相似文献
957.
Nitrogen loss from unpolluted South American forests mainly via dissolved organic compounds. 总被引:54,自引:0,他引:54
Conceptual and numerical models of nitrogen cycling in temperate forests assume that nitrogen is lost from these ecosystems predominantly by way of inorganic forms, such as nitrate and ammonium ions. Of these, nitrate is thought to be particularly mobile, being responsible for nitrogen loss to deep soil and stream waters. But human activities-such as fossil fuel combustion, fertilizer production and land-use change-have substantially altered the nitrogen cycle over large regions, making it difficult to separate natural aspects of nitrogen cycling from those induced by human perturbations. Here we report stream chemistry data from 100 unpolluted primary forests in temperate South America. Although the sites exhibit a broad range of environmental factors that influence ecosystem nutrient cycles (such as climate, parent material, time of ecosystem development, topography and biotic diversity), we observed a remarkably consistent pattern of nitrogen loss across all forests. In contrast to findings from forests in polluted regions, streamwater nitrate concentrations are exceedingly low, such that nitrate to ammonium ratios were less than unity, and dissolved organic nitrogen is responsible for the majority of nitrogen losses from these forests. We therefore suggest that organic nitrogen losses should be considered in models of forest nutrient cycling, which could help to explain observations of nutrient limitation in temperate forest ecosystems. 相似文献
958.
顾成扬 《淮阴师范学院学报(自然科学版)》2002,1(3):6-9
本文给出完全图Kn和完全多部图Kn(t)存在{C3, S4}-强制分解的充分必要条件. 相似文献
959.
Sox9 induces testis development in XX transgenic mice. 总被引:18,自引:0,他引:18
Mutations in SOX9 are associated with male-to-female sex reversal in humans. To analyze Sox9 function during sex determination, we ectopically expressed this gene in XX gonads. Here, we show that Sox9 is sufficient to induce testis formation in mice, indicating that it can substitute for the sex-determining gene Sry. 相似文献
960.