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排序方式: 共有2034条查询结果,搜索用时 17 毫秒
941.
942.
Belen Hurle Tomas Marques-Bonet Francesca Antonacci Inna Hughes Joseph F Ryan NISC Comparative Sequencing Program Evan E Eichler David M Ornitz Eric D Green 《BMC evolutionary biology》2011,11(1):23
Background
Mutations in the Otopetrin 1 gene (Otop1) in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP) family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH) subtype 1G (Ush1g), both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. 相似文献943.
Church DM Schneider VA Graves T Auger K Cunningham F Bouk N Chen HC Agarwala R McLaren WM Ritchie GR Albracht D Kremitzki M Rock S Kotkiewicz H Kremitzki C Wollam A Trani L Fulton L Fulton R Matthews L Whitehead S Chow W Torrance J Dunn M Harden G Threadgold G Wood J Collins J Heath P Griffiths G Pelan S Grafham D Eichler EE Weinstock G Mardis ER Wilson RK Howe K Flicek P Hubbard T 《PLoS biology》2011,9(7):e1001091
944.
Limitations of next-generation genome sequence assembly 总被引:1,自引:0,他引:1
High-throughput sequencing technologies promise to transform the fields of genetics and comparative biology by delivering tens of thousands of genomes in the near future. Although it is feasible to construct de novo genome assemblies in a few months, there has been relatively little attention to what is lost by sole application of short sequence reads. We compared the recent de novo assemblies using the short oligonucleotide analysis package (SOAP), generated from the genomes of a Han Chinese individual and a Yoruban individual, to experimentally validated genomic features. We found that de novo assemblies were 16.2% shorter than the reference genome and that 420.2 megabase pairs of common repeats and 99.1% of validated duplicated sequences were missing from the genome. Consequently, over 2,377 coding exons were completely missing. We conclude that high-quality sequencing approaches must be considered in conjunction with high-throughput sequencing for comparative genomics analyses and studies of genome evolution. 相似文献
945.
Amyloid-β amyloidogenesis is reported to occur via a nucleated polymerization mechanism. If this is true, the energetically unfavorable oligomeric nucleus should be very hard to detect. However, many laboratories have detected early nonfibrillar amyloid-β oligomers without observing amyloid fibrils, suggesting that a mechanistic revision may be needed. Here we introduce Cys-Cys-amyloid-β(1-40), which cannot bind to the latent fluorophore FlAsH as a monomer, but can bind FlAsH as an nonfibrillar oligomer or as a fibril, rendering the conjugates fluorescent. Through FlAsH monitoring of Cys-Cys-amyloid-β(1-40) aggregation, we found that amyloid-β(1-40) rapidly and efficiently forms spherical oligomers in vitro (85% yield) that are kinetically competent to slowly convert to amyloid fibrils by a nucleated conformational conversion mechanism. This methodology was used to show that plasmalogen ethanolamine vesicles eliminate the proteotoxicity-associated oligomerization phase of amyloid-β amyloidogenesis while allowing fibril formation, rationalizing how low concentrations of plasmalogen ethanolamine in the brain are epidemiologically linked to Alzheimer's disease. 相似文献
946.
Olsson M Meadows JR Truvé K Rosengren Pielberg G Puppo F Mauceli E Quilez J Tonomura N Zanna G Docampo MJ Bassols A Avery AC Karlsson EK Thomas A Kastner DL Bongcam-Rudloff E Webster MT Sanchez A Hedhammar A Remmers EF Andersson L Ferrer L Tintle L Lindblad-Toh K 《PLoS genetics》2011,7(3):e1001332
Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation. 相似文献
947.
948.
Zetterberg H Mörtberg E Song L Chang L Provuncher GK Patel PP Ferrell E Fournier DR Kan CW Campbell TG Meyer R Rivnak AJ Pink BA Minnehan KA Piech T Rissin DM Duffy DC Rubertsson S Wilson DH Blennow K 《PloS one》2011,6(12):e28263
Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD. 相似文献
949.
Siddappa NB Hemashettar G Shanmuganathan V Semenya AA Sweeney ED Paul KS Lee SJ Secor WE Ruprecht RM 《PLoS neglected tropical diseases》2011,5(8):e1270
Background
The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase host susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased susceptibility to SHIV-C acquisition, a similarly large difference in host susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased host susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys.Methods and Findings
We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P<0.001 for both). The lack of significant differences after the i.v. challenge implies that the increased host susceptibility is predominantly due to parasite-mediated mucosal upregulation of virus replication and spread, rather than systemic effects.Conclusions
The major impact of schistosome-induced increased host susceptibility is at the mucosal level. Given that >90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1. 相似文献950.
Meeting cholera's challenge to Haiti and the world: a joint statement on cholera prevention and care
Farmer P Almazor CP Bahnsen ET Barry D Bazile J Bloom BR Bose N Brewer T Calderwood SB Clemens JD Cravioto A Eustache E Jérôme G Gupta N Harris JB Hiatt HH Holstein C Hotez PJ Ivers LC Kerry VB Koenig SP Larocque RC Léandre F Lambert W Lyon E Mekalanos JJ Mukherjee JS Oswald C Pape JW Gretchko Prosper A Rabinovich R Raymonville M Réjouit JR Ronan LJ Rosenberg ML Ryan ET Sachs JD Sack DA Surena C Suri AA Ternier R Waldor MK Walton D Weigel JL 《PLoS neglected tropical diseases》2011,5(5):e1145