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排序方式: 共有643条查询结果,搜索用时 22 毫秒
411.
Lindblad-Toh K Wade CM Mikkelsen TS Karlsson EK Jaffe DB Kamal M Clamp M Chang JL Kulbokas EJ Zody MC Mauceli E Xie X Breen M Wayne RK Ostrander EA Ponting CP Galibert F Smith DR DeJong PJ Kirkness E Alvarez P Biagi T Brockman W Butler J Chin CW Cook A Cuff J Daly MJ DeCaprio D Gnerre S Grabherr M Kellis M Kleber M Bardeleben C Goodstadt L Heger A Hitte C Kim L Koepfli KP Parker HG Pollinger JP Searle SM Sutter NB Thomas R Webber C Baldwin J Abebe A Abouelleil A Aftuck L Ait-Zahra M Aldredge T 《Nature》2005,438(7069):803-819
Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health. 相似文献
412.
A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange 总被引:3,自引:0,他引:3
Liu Y Dentin R Chen D Hedrick S Ravnskjaer K Schenk S Milne J Meyers DJ Cole P Yates J Olefsky J Guarente L Montminy M 《Nature》2008,456(7219):269-273
413.
414.
Kumar P Wu H McBride JL Jung KE Kim MH Davidson BL Lee SK Shankar P Manjunath N 《Nature》2007,448(7149):39-43
A major impediment in the treatment of neurological diseases is the presence of the blood-brain barrier, which precludes the entry of therapeutic molecules from blood to brain. Here we show that a short peptide derived from rabies virus glycoprotein (RVG) enables the transvascular delivery of small interfering RNA (siRNA) to the brain. This 29-amino-acid peptide specifically binds to the acetylcholine receptor expressed by neuronal cells. To enable siRNA binding, a chimaeric peptide was synthesized by adding nonamer arginine residues at the carboxy terminus of RVG. This RVG-9R peptide was able to bind and transduce siRNA to neuronal cells in vitro, resulting in efficient gene silencing. After intravenous injection into mice, RVG-9R delivered siRNA to the neuronal cells, resulting in specific gene silencing within the brain. Furthermore, intravenous treatment with RVG-9R-bound antiviral siRNA afforded robust protection against fatal viral encephalitis in mice. Repeated administration of RVG-9R-bound siRNA did not induce inflammatory cytokines or anti-peptide antibodies. Thus, RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood-brain barrier. 相似文献
415.
416.
Duy C Hurtz C Shojaee S Cerchietti L Geng H Swaminathan S Klemm L Kweon SM Nahar R Braig M Park E Kim YM Hofmann WK Herzog S Jumaa H Koeffler HP Yu JJ Heisterkamp N Graeber TG Wu H Ye BH Melnick A Müschen M 《Nature》2011,473(7347):384-388
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones. 相似文献
417.
Choe HW Kim YJ Park JH Morizumi T Pai EF Krauss N Hofmann KP Scheerer P Ernst OP 《Nature》2011,471(7340):651-655
G-protein-coupled receptors (GPCRs) are seven transmembrane helix (TM) proteins that transduce signals into living cells by binding extracellular ligands and coupling to intracellular heterotrimeric G proteins (Gαβγ). The photoreceptor rhodopsin couples to transducin and bears its ligand 11-cis-retinal covalently bound via a protonated Schiff base to the opsin apoprotein. Absorption of a photon causes retinal cis/trans isomerization and generates the agonist all-trans-retinal in situ. After early photoproducts, the active G-protein-binding intermediate metarhodopsin II (Meta?II) is formed, in which the retinal Schiff base is still intact but deprotonated. Dissociation of the proton from the Schiff base breaks a major constraint in the protein and enables further activating steps, including an outward tilt of TM6 and formation of a large cytoplasmic crevice for uptake of the interacting C terminus of the Gα subunit. Owing to Schiff base hydrolysis, Meta?II is short-lived and notoriously difficult to crystallize. We therefore soaked opsin crystals with all-trans-retinal to form Meta?II, presuming that the crystal's high concentration of opsin in an active conformation (Ops*) may facilitate all-trans-retinal uptake and Schiff base formation. Here we present the 3.0?? and 2.85?? crystal structures, respectively, of Meta?II alone or in complex with an 11-amino-acid C-terminal fragment derived from Gα (GαCT2). GαCT2 binds in a large crevice at the cytoplasmic side, akin to the binding of a similar Gα-derived peptide to Ops* (ref. 7). In the Meta?II structures, the electron density from the retinal ligand seamlessly continues into the Lys?296 side chain, reflecting proper formation of the Schiff base linkage. The retinal is in a relaxed conformation and almost undistorted compared with pure crystalline all-trans-retinal. By comparison with early photoproducts we propose how retinal translocation and rotation induce the gross conformational changes characteristic for Meta?II. The structures can now serve as models for the large GPCR family. 相似文献
418.
Genome sequencing reveals insights into physiology and longevity of the naked mole rat 总被引:1,自引:0,他引:1
Kim EB Fang X Fushan AA Huang Z Lobanov AV Han L Marino SM Sun X Turanov AA Yang P Yim SH Zhao X Kasaikina MV Stoletzki N Peng C Polak P Xiong Z Kiezun A Zhu Y Chen Y Kryukov GV Zhang Q Peshkin L Yang L Bronson RT Buffenstein R Wang B Han C Li Q Chen L Zhao W Sunyaev SR Park TJ Zhang G Wang J Gladyshev VN 《Nature》2011,479(7372):223-227
419.
The Open Service Gateway Initiative (OSGi) has played an important role in ubiquitous environments that support interoperability among embedded devices, such as home appliances and network devices. However, the OSGi does not have a common event mechanism yet, and it is difficult to communicate among services asynchronously. In the present work, a common event manager, Aspect-Oriented Event Manager (AOEM), was designed on an OSGi framework. AOEM supports services to generate and provide notification of events. This paper presents the implementation of AOEM as an OSGi bundle with AspectJ. The experiment on transferring between device service and application service demonstrate that AOEM provides good abstraction of the services and convenience. 相似文献
420.
This paper presents an autoregressive fractionally integrated moving‐average (ARFIMA) model of nominal exchange rates and compares its forecasting capability with the monetary structural models and the random walk model. Monthly observations are used for Canada, France, Germany, Italy, Japan and the United Kingdom for the period of April 1973 through December 1998. The estimation method is Sowell's (1992) exact maximum likelihood estimation. The forecasting accuracy of the long‐memory model is formally compared to the random walk and the monetary models, using the recently developed Harvey, Leybourne and Newbold (1997) test statistics. The results show that the long‐memory model is more efficient than the random walk model in steps‐ahead forecasts beyond 1 month for most currencies and more efficient than the monetary models in multi‐step‐ahead forecasts. This new finding strongly suggests that the long‐memory model of nominal exchange rates be studied as a viable alternative to the conventional models. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献