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Young H. Lim Jonathan M. Fisher Keith A. Choate 《Cellular and molecular life sciences : CMLS》2017,74(12):2229-2238
Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual’s lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this “natural gene therapy”. 相似文献
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The proteins Cdc42 and Rac are members of the Rho family of small GTPases (G proteins), which control signal-transduction pathways that lead to rearrangements of the cell cytoskeleton, cell differentiation and cell proliferation. They do so by binding to downstream effector proteins. Some of these, known as CRIB (for Cdc42/Rac interactive-binding) proteins, bind to both Cdc42 and Rac, such as the PAK1-3 serine/threonine kinases, whereas others are specific for Cdc42, such as the ACK tyrosine kinases and the Wiscott-Aldrich-syndrome proteins (WASPs). The effector loop of Cdc42 and Rac (comprising residues 30-40, also called switch I), is one of two regions which change conformation on exchange of GDP for GTP. This region is almost identical in Cdc42 and Racs, indicating that it does not determine the specificity of these G proteins. Here we report the solution structure of the complex of Cdc42 with the GTPase-binding domain ofACK. Both proteins undergo significant conformational changes on binding, to form a new type of G-protein/effector complex. The interaction extends the beta-sheet in Cdc42 by binding an extended strand from ACK, as seen in Ras/effector interactions, but it also involves other regions of the G protein that are important for determining the specificity of effector binding. 相似文献
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The geometric correction of a satellite imagery is performed by making a systematic correction with satellite ephemerides and attitude angles followed by employing the Ground Control Points (GCPs) or Digital Elevation Models (DEMs). In a remote area or an inaccessible area, however,GCPs are unavailable to be surveyed and thus they can be obtained only by reading maps, which is not accurate in reality.In this study, we performed the systematic correction process to the inaccessible area and the precise geometric correction process to the adjacent accessible area by using GCPs. Then we analyzed the correlation between the two geo-referenced Korea Multipurpose Satellite (KOMPSAT-1 EOC) images. A new geometrical correction for the inaccessible area imagery is achieved by applying the correlation to the inaccessible imagery. By employing this new method, the accuracy of the inaccessible area imagery is significantly improved absolutely and relatively. 相似文献
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Epidemiological studies establish a link between Type 2 diabetes (T2DM) and Alzheimer’s disease (AD), both leading causes
of morbidity and mortality in the elderly. These diseases also share clinical and biochemical features suggesting common pathogenic
mechanisms. Specifically, both are amyloidoses as they are characterized by fibrillar protein aggregates – amylin in T2DM
pancreatic islets, and β-amyloid (Aβ) and neurofibrillary tangles (NFTs) in AD brain. Amylin aggregation is associated with
pancreatic β-cell loss, and Aβ and NFT formation with neuronal cell loss. We discuss the possibility that amylin and Aβ exert
their toxicity by similar mechanisms, with components of the pathocascades shared, and that therapies based on amyloidogenic
properties are beneficial for both T2DM and AD.
Received 27 January 2009; received after revision 17 February 2009; accepted 23 February 2009 相似文献
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In many prokaryotes and eukaryotes, DNA methylation at cis-regulatory sequences determines whether gene expression is on or off. Stable inheritance of these expression states is required in bacterial pathogenesis, cancer and developmental pathways. Here we delineate the factors that control the stability of these states by using the agn43 gene in Escherichia coli as a model system. Systematic disruption of this system shows that a functional switch requires the presence of several, rarely occupied, intermediate states that separate the 'on' and 'off' states. Cells that leave the on and off state enter different intermediate states, where there is a strong bias that drives cells back to their original state. The intermediate states therefore act as buffers that prevent back and forth switching. This mechanism of generating multiple states is an alternative to feedback regulation, and its general principle should be applicable to the analysis of other epigenetic switches and the design of synthetic circuits. 相似文献
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Jeon J Park SY Chi MH Choi J Park J Rho HS Kim S Goh J Yoo S Choi J Park JY Yi M Yang S Kwon MJ Han SS Kim BR Khang CH Park B Lim SE Jung K Kong S Karunakaran M Oh HS Kim H Kim S Park J Kang S Choi WB Kang S Lee YH 《Nature genetics》2007,39(4):561-565
Rapid translation of genome sequences into meaningful biological information hinges on the integration of multiple experimental and informatics methods into a cohesive platform. Despite the explosion in the number of genome sequences available, such a platform does not exist for filamentous fungi. Here we present the development and application of a functional genomics and informatics platform for a model plant pathogenic fungus, Magnaporthe oryzae. In total, we produced 21,070 mutants through large-scale insertional mutagenesis using Agrobacterium tumefaciens-mediated transformation. We used a high-throughput phenotype screening pipeline to detect disruption of seven phenotypes encompassing the fungal life cycle and identified the mutated gene and the nature of mutation for each mutant. Comparative analysis of phenotypes and genotypes of the mutants uncovered 202 new pathogenicity loci. Our findings demonstrate the effectiveness of our platform and provide new insights on the molecular basis of fungal pathogenesis. Our approach promises comprehensive functional genomics in filamentous fungi and beyond. 相似文献