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排序方式: 共有288条查询结果,搜索用时 15 毫秒
281.
Keane TM Goodstadt L Danecek P White MA Wong K Yalcin B Heger A Agam A Slater G Goodson M Furlotte NA Eskin E Nellåker C Whitley H Cleak J Janowitz D Hernandez-Pliego P Edwards A Belgard TG Oliver PL McIntyre RE Bhomra A Nicod J Gan X Yuan W van der Weyden L Steward CA Bala S Stalker J Mott R Durbin R Jackson IJ Czechanski A Guerra-Assunção JA Donahue LR Reinholdt LG Payseur BA Ponting CP Birney E Flint J Adams DJ 《Nature》2011,477(7364):289-294
282.
Young ND Debellé F Oldroyd GE Geurts R Cannon SB Udvardi MK Benedito VA Mayer KF Gouzy J Schoof H Van de Peer Y Proost S Cook DR Meyers BC Spannagl M Cheung F De Mita S Krishnakumar V Gundlach H Zhou S Mudge J Bharti AK Murray JD Naoumkina MA Rosen B Silverstein KA Tang H Rombauts S Zhao PX Zhou P Barbe V Bardou P Bechner M Bellec A Berger A Bergès H Bidwell S Bisseling T Choisne N Couloux A Denny R Deshpande S Dai X Doyle JJ Dudez AM Farmer AD Fouteau S Franken C Gibelin C Gish J Goldstein S 《Nature》2011,480(7378):520-524
Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ~94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox. 相似文献
283.
Breitbach CJ Burke J Jonker D Stephenson J Haas AR Chow LQ Nieva J Hwang TH Moon A Patt R Pelusio A Le Boeuf F Burns J Evgin L De Silva N Cvancic S Robertson T Je JE Lee YS Parato K Diallo JS Fenster A Daneshmand M Bell JC Kirn DH 《Nature》2011,477(7362):99-102
The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans. 相似文献
284.
Greer EL Maures TJ Ucar D Hauswirth AG Mancini E Lim JP Benayoun BA Shi Y Brunet A 《Nature》2011,479(7373):365-371
Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histone methyltransferase SET-2, regulates Caenorhabditis elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendants. 相似文献
285.
Xu SZ Sukumar P Zeng F Li J Jairaman A English A Naylor J Ciurtin C Majeed Y Milligan CJ Bahnasi YM Al-Shawaf E Porter KE Jiang LH Emery P Sivaprasadarao A Beech DJ 《Nature》2008,451(7174):69-72
Mammalian homologues of Drosophila melanogaster transient receptor potential (TRP) are a large family of multimeric cation channels that act, or putatively act, as sensors of one or more chemical factor. Major research objectives are the identification of endogenous activators and the determination of cellular and tissue functions of these channels. Here we show the activation of TRPC5 (canonical TRP 5) homomultimeric and TRPC5-TRPC1 heteromultimeric channels by extracellular reduced thioredoxin, which acts by breaking a disulphide bridge in the predicted extracellular loop adjacent to the ion-selectivity filter of TRPC5. Thioredoxin is an endogenous redox protein with established intracellular functions, but it is also secreted and its extracellular targets are largely unknown. Particularly high extracellular concentrations of thioredoxin are apparent in rheumatoid arthritis, an inflammatory joint disease that disables millions of people worldwide. We show that TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis, that endogenous TRPC5-TRPC1 channels of the cells are activated by reduced thioredoxin, and that blockade of the channels enhances secretory activity and prevents the suppression of secretion by thioredoxin. The data indicate the presence of a previously unrecognized ion-channel activation mechanism that couples extracellular thioredoxin to cell function. 相似文献
286.
The Bicoid (Bcd) gradient in Drosophila has long been a model for the action of a morphogen in establishing embryonic polarity. However, it is now clear that bcd is a unique feature of higher Diptera. An evolutionarily ancient gene, orthodenticle (otd), has a bcd-like role in the beetle Tribolium. Unlike the Bcd gradient, which arises by diffusion of protein from an anteriorly localized messenger RNA, the Tribolium Otd gradient forms by translational repression of otd mRNA by a posteriorly localized factor. These differences in gradient formation are correlated with differences in modes of embryonic patterning. Drosophila uses long germ embryogenesis, where the embryo derives from the entire anterior-posterior axis, and all segments are patterned at the blastoderm stage, before gastrulation. In contrast, Tribolium undergoes short germ embryogenesis: the embryo arises from cells in the posterior of the egg, and only anterior segments are patterned at the blastoderm stage, with the remaining segments arising after gastrulation from a growth zone. Here we describe the role of otd in the long germband embryo of the wasp Nasonia vitripennis. We show that Nasonia otd maternal mRNA is localized at both poles of the embryo, and resulting protein gradients pattern both poles. Thus, localized Nasonia otd has two major roles that allow long germ development. It activates anterior targets at the anterior of the egg in a manner reminiscent of the Bcd gradient, and it is required for pre-gastrulation expression of posterior gap genes. 相似文献
287.
Scherer SE Muzny DM Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Montgomery KT Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Lovering RC Wheeler DA Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clerc-Blankenburg KP Davis C Delgado O Dinh HH Draper H Gonzalez-Garay ML Havlak P Jackson LR Jacob LS 《Nature》2006,440(7082):346-351
Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents. 相似文献
288.
Dong C Beis K Nesper J Brunkan-Lamontagne AL Clarke BR Whitfield C Naismith JH 《Nature》2006,444(7116):226-229
Many types of bacteria produce extracellular polysaccharides (EPSs). Some are secreted polymers and show only limited association with the cell surface, whereas others are firmly attached to the cell surface and form a discrete structural layer, the capsule, which envelopes the cell and allows the bacteria to evade or counteract the host immune system. EPSs have critical roles in bacterial colonization of surfaces, such as epithelia and medical implants; in addition some EPSs have important industrial and biomedical applications in their own right. Here we describe the 2.26 A resolution structure of the 340 kDa octamer of Wza, an integral outer membrane lipoprotein, which is essential for group 1 capsule export in Escherichia coli. The transmembrane region is a novel alpha-helical barrel. The bulk of the Wza structure is located in the periplasm and comprises three novel domains forming a large central cavity. Wza is open to the extracellular environment but closed to the periplasm. We propose a route and mechanism for translocation of the capsular polysaccharide. This work may provide insight into the export of other large polar molecules such as DNA and proteins. 相似文献