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101.
102.
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
103.
An Erratum has been published for this article in Journal of Forecasting 23(6): 461 (2004) . This paper examines the problem of intrusion in computer systems that causes major breaches or allows unauthorized information manipulation. A new intrusion‐detection system using Bayesian multivariate regression is proposed to predict such unauthorized invasions before they occur and to take further action. We develop and use a multivariate dynamic linear model based on a unique approach leaving the unknown observational variance matrix distribution unspecified. The result is simultaneous forecasting free of the Wishart limitations that is proved faster and more reliable. Our proposed system uses software agent technology. The distributed software agent environment places an agent in each of the computer system workstations. The agent environment creates a user profile for each user. Every user has his or her profile monitored by the agent system and according to our statistical model prediction is possible. Implementation aspects are discussed using real data and an assessment of the model is provided. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
104.
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
105.
K. O. John 《Cellular and molecular life sciences : CMLS》1971,27(5):517-519
Résumé Le muscle pectoral duDraco dussumieri comprend des fibres de trois sortes: minces, intermédiaires et épaisses. Les fibres minces sont adaptées à un métabolisme glycolytique et les fibres épaisses au lipolytique. L'activité des fibres minces révèle la présence de phosphorylase et de synthétase glycogénique. 相似文献
106.
Archaeopteryx, the earliest known flying bird (avialan) from the Late Jurassic period, exhibits many shared primitive characters with more basal coelurosaurian dinosaurs (the clade including all theropods more bird-like than Allosaurus), such as teeth, a long bony tail and pinnate feathers. However, Archaeopteryx possessed asymmetrical flight feathers on its wings and tail, together with a wing feather arrangement shared with modern birds. This suggests some degree of powered flight capability but, until now, little was understood about the extent to which its brain and special senses were adapted for flight. We investigated this problem by computed tomography scanning and three-dimensional reconstruction of the braincase of the London specimen of Archaeopteryx. Here we show the reconstruction of the braincase from which we derived endocasts of the brain and inner ear. These suggest that Archaeopteryx closely resembled modern birds in the dominance of the sense of vision and in the possession of expanded auditory and spatial sensory perception in the ear. We conclude that Archaeopteryx had acquired the derived neurological and structural adaptations necessary for flight. An enlarged forebrain suggests that it had also developed enhanced somatosensory integration with these special senses demanded by a lifestyle involving flying ability. 相似文献
107.
One of the central challenges of evolutionary biology is to understand how coevolution organizes biodiversity over complex geographic landscapes. Most species are collections of genetically differentiated populations, and these populations have the potential to become adapted to their local environments in different ways. The geographic mosaic theory of coevolution incorporates this idea by proposing that spatial variation in natural selection and gene flow across a landscape can shape local coevolutionary dynamics. These effects may be particularly strong when populations differ across productivity gradients, where gene flow will often be asymmetric among populations. Conclusive empirical tests of this theory have been particularly difficult to perform because they require knowledge of patterns of gene flow, historical population relationships and local selection pressures. We have tested these predictions empirically using a model community of bacteria and bacteriophage (viral parasitoids of bacteria). We show that gene flow across a spatially structured landscape alters coevolution of parasitoids and their hosts and that the resulting patterns of adaptation can fluctuate in both space and time. 相似文献
108.
109.
The role of barren stalk1 in the architecture of maize 总被引:4,自引:0,他引:4
Gallavotti A Zhao Q Kyozuka J Meeley RB Ritter MK Doebley JF Pè ME Schmidt RJ 《Nature》2004,432(7017):630-635
The architecture of higher plants is established through the activity of lateral meristems--small groups of stem cells formed during vegetative and reproductive development. Lateral meristems generate branches and inflorescence structures, which define the overall form of a plant, and are largely responsible for the evolution of different plant architectures. Here, we report the isolation of the barren stalk1 gene, which encodes a non-canonical basic helix-loop-helix protein required for the initiation of all aerial lateral meristems in maize. barren stalk1 represents one of the earliest genes involved in the patterning of maize inflorescences, and, together with the teosinte branched1 gene, it regulates vegetative lateral meristem development. The architecture of maize has been a major target of selection for early agriculturalists and modern farmers, because it influences harvesting, breeding strategies and mechanization. By sampling nucleotide diversity in the barren stalk1 region, we show that two haplotypes entered the maize gene pool from its wild progenitor, teosinte, and that only one was incorporated throughout modern inbreds, suggesting that barren stalk1 was selected for agronomic purposes. 相似文献
110.
Mechelli A Crinion JT Noppeney U O'Doherty J Ashburner J Frackowiak RS Price CJ 《Nature》2004,431(7010):757
Humans have a unique ability to learn more than one language--a skill that is thought to be mediated by functional (rather than structural) plastic changes in the brain. Here we show that learning a second language increases the density of grey matter in the left inferior parietal cortex and that the degree of structural reorganization in this region is modulated by the proficiency attained and the age at acquisition. This relation between grey-matter density and performance may represent a general principle of brain organization. 相似文献