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排序方式: 共有804条查询结果,搜索用时 406 毫秒
191.
192.
Volkman SK Sabeti PC DeCaprio D Neafsey DE Schaffner SF Milner DA Daily JP Sarr O Ndiaye D Ndir O Mboup S Duraisingh MT Lukens A Derr A Stange-Thomann N Waggoner S Onofrio R Ziaugra L Mauceli E Gnerre S Jaffe DB Zainoun J Wiegand RC Birren BW Hartl DL Galagan JE Lander ES Wirth DF 《Nature genetics》2007,39(1):113-119
Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite. 相似文献
193.
He XC Yin T Grindley JC Tian Q Sato T Tao WA Dirisina R Porter-Westpfahl KS Hembree M Johnson T Wiedemann LM Barrett TA Hood L Wu H Li L 《Nature genetics》2007,39(2):189-198
Intestinal polyposis, a precancerous neoplasia, results primarily from an abnormal increase in the number of crypts, which contain intestinal stem cells (ISCs). In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement. Using this model, we have established the relationship between stem cells and polyp and tumor formation. PTEN helps govern the proliferation rate and number of ISCs and loss of PTEN results in an excess of ISCs. In PTEN-deficient mice, excess ISCs initiate de novo crypt formation and crypt fission, recapitulating crypt production in fetal and neonatal intestine. The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector beta-catenin. Akt phosphorylates beta-catenin at Ser552, resulting in a nuclear-localized form in ISCs. Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin. 相似文献
194.
Croker B Crozat K Berger M Xia Y Sovath S Schaffer L Eleftherianos I Imler JL Beutler B 《Nature genetics》2007,39(12):1453-1460
Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors. 相似文献
195.
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy 总被引:14,自引:0,他引:14
Pandit B Sarkozy A Pennacchio LA Carta C Oishi K Martinelli S Pogna EA Schackwitz W Ustaszewska A Landstrom A Bos JM Ommen SR Esposito G Lepri F Faul C Mundel P López Siguero JP Tenconi R Selicorni A Rossi C Mazzanti L Torrente I Marino B Digilio MC Zampino G Ackerman MJ Dallapiccola B Tartaglia M Gelb BD 《Nature genetics》2007,39(8):1007-1012
Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy. 相似文献
196.
Cyclic GMP is involved in the excitation of invertebrate photoreceptors 总被引:13,自引:0,他引:13
The hyperpolarizing receptor potential in vertebrate rod photoreceptors appears to be mediated by the second messenger, cyclic GMP. Injection of cGMP into rods or application of cGMP to inside-out membrane patches activates a conductance resembling that produced by light. Light produces a rapid reduction of cGMP in living rods, leading to closure of sodium channels and membrane hyperpolarization. In most invertebrate photoreceptors the response to light is depolarizing. We have investigated whether cGMP is involved in controlling the increase in sodium conductance that underlies this depolarization. We show here that injection of cGMP into Limulus photoreceptors produces a depolarization that mimics the receptor potential. We also show that the cGMP concentration of the squid retina increases rapidly during exposure to light. These results support the hypothesis that cGMP mediates the light-induced depolarization in invertebrate photoreceptors and suggests that vertebrate and invertebrate phototransduction may be more similar than previously thought. 相似文献
197.
198.
Until now, the analysis of burrowing mechanics has neglected the mechanical properties of impeding, muddy, cohesive sediments, which behave like elastic solids. Here we show that burrowers can progress through such sediments by using a mechanically efficient, previously unsuspected mechanism--crack propagation--in which an alternating 'anchor' system of burrowing serves as a wedge to extend the crack-shaped burrow. The force required to propagate cracks through sediment in this way is relatively small: we find that the force exerted by the annelid worm Nereis virens in making and moving into such a burrow amounts to less than one-tenth of the force it needs to use against rigid aquarium walls. 相似文献
199.
Speciation in animals is almost always envisioned as the split of an existing lineage into an ancestral and a derived species. An alternative speciation route is homoploid hybrid speciation in which two ancestral taxa give rise to a third, derived, species by hybridization without a change in chromosome number. Although theoretically possible it has been regarded as rare and hence of little importance in animals. On the basis of molecular and chromosomal evidence, hybridization is the best explanation for the origin of a handful of extant diploid bisexual animal taxa. Here we report the first case in which hybridization between two host-specific animals (tephritid fruitflies) is clearly associated with the shift to a new resource. Such a hybrid host shift presents an ecologically robust scenario for animal hybrid speciation because it offers a potential mechanism for reproductive isolation through differential adaptation to a new ecological niche. The necessary conditions for this mechanism of speciation are common in parasitic animals, which represent much of animal diversity. The frequency of homoploid hybrid speciation in animals may therefore be higher than previously assumed. 相似文献
200.
The genome of the social amoeba Dictyostelium discoideum 总被引:2,自引:0,他引:2
Eichinger L Pachebat JA Glöckner G Rajandream MA Sucgang R Berriman M Song J Olsen R Szafranski K Xu Q Tunggal B Kummerfeld S Madera M Konfortov BA Rivero F Bankier AT Lehmann R Hamlin N Davies R Gaudet P Fey P Pilcher K Chen G Saunders D Sodergren E Davis P Kerhornou A Nie X Hall N Anjard C Hemphill L Bason N Farbrother P Desany B Just E Morio T Rost R Churcher C Cooper J Haydock S van Driessche N Cronin A Goodhead I Muzny D Mourier T Pain A Lu M Harper D Lindsay R Hauser H James K Quiles M 《Nature》2005,435(7038):43-57
The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi. 相似文献