排序方式: 共有49条查询结果,搜索用时 15 毫秒
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PTC124 targets genetic disorders caused by nonsense mutations 总被引:1,自引:0,他引:1
Welch EM Barton ER Zhuo J Tomizawa Y Friesen WJ Trifillis P Paushkin S Patel M Trotta CR Hwang S Wilde RG Karp G Takasugi J Chen G Jones S Ren H Moon YC Corson D Turpoff AA Campbell JA Conn MM Khan A Almstead NG Hedrick J Mollin A Risher N Weetall M Yeh S Branstrom AA Colacino JM Babiak J Ju WD Hirawat S Northcutt VJ Miller LL Spatrick P He F Kawana M Feng H Jacobson A Peltz SW Sweeney HL 《Nature》2007,447(7140):87-91
Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options. 相似文献
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Kozyrev SV Abelson AK Wojcik J Zaghlool A Linga Reddy MV Sanchez E Gunnarsson I Svenungsson E Sturfelt G Jönsen A Truedsson L Pons-Estel BA Witte T D'Alfonso S Barizzone N Barrizzone N Danieli MG Gutierrez C Suarez A Junker P Laustrup H González-Escribano MF Martin J Abderrahim H Alarcón-Riquelme ME 《Nature genetics》2008,40(2):211-216
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Maternal control of resting-egg production in Daphnia. 总被引:1,自引:0,他引:1
Many planktonic organisms produce 'resting' stages when the environmental conditions deteriorate. Like seeds, resting stages can survive unfavourable conditions. The crustacean Daphnia normally reproduces by means of parthenogenetically produced normal, not resting, eggs-but occasionally switches to bisexual reproduction, which results in two resting eggs encased in a robust structure carried on the back of the female. This 'ephippium' is shed with the next moult, and can survive dormant for many years. The induction of resting-egg production requires multiple environmental stimuli, one of them being photoperiod. The switch from production of parthenogenetic eggs to resting eggs in Daphnia has recently been shown to be influenced by a maternal food effect. Here we present evidence that female Daphnia transmit information not only about food but also on photoperiod to their offspring, and influence the production of resting eggs in the next generation. The combined maternal effects can be relevant for the correct timing of resting-egg production-for example, in discriminating between spring and autumn conditions. 相似文献
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S.多罗费伍 《国外科技新书评介》2007,(2):3-4
在社会和商业等调查中所采用的样本通常并不如人们想象的那么随机,这种非随机性可能会影响由调查数据中得出的结论。 相似文献
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Channel plasmon subwavelength waveguide components including interferometers and ring resonators 总被引:4,自引:0,他引:4
Photonic components are superior to electronic ones in terms of operational bandwidth, but the diffraction limit of light poses a significant challenge to the miniaturization and high-density integration of optical circuits. The main approach to circumvent this problem is to exploit the hybrid nature of surface plasmon polaritons (SPPs), which are light waves coupled to free electron oscillations in a metal that can be laterally confined below the diffraction limit using subwavelength metal structures. However, the simultaneous realization of strong confinement and a propagation loss sufficiently low for practical applications has long been out of reach. Channel SPP modes--channel plasmon polaritons (CPPs)--are electromagnetic waves that are bound to and propagate along the bottom of V-shaped grooves milled in a metal film. They are expected to exhibit useful subwavelength confinement, relatively low propagation loss, single-mode operation and efficient transmission around sharp bends. Our previous experiments showed that CPPs do exist and that they propagate over tens of micrometres along straight subwavelength grooves. Here we report the design, fabrication and characterization of CPP-based subwavelength waveguide components operating at telecom wavelengths: Y-splitters, Mach-Zehnder interferometers and waveguide-ring resonators. We demonstrate that CPP guides can indeed be used for large-angle bending and splitting of radiation, thereby enabling the realization of ultracompact plasmonic components and paving the way for a new class of integrated optical circuits. 相似文献
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The standard cosmological model, now strongly constrained by direct observations of the Universe at early epochs, is very successful in describing the evolution of structure on large and intermediate scales. Unfortunately, serious contradictions remain on smaller, galactic scales. Among the main small-scale problems is a significant and persistent discrepancy between observations of nearby galaxies, which imply that galactic dark matter haloes have a density profile with a flat core, and the cosmological model, which predicts that the haloes should have divergent density (a cusp) at the centre. Here we report numerical simulations that show that random bulk motions of gas in small primordial galaxies, of the magnitude expected in these systems, will result in a flattening of the central dark matter cusp on relatively short timescales (approximately 10(8) years). Gas bulk motions in early galaxies are driven by supernova explosions that result from ongoing star formation. Our mechanism is general, and would have operated in all star-forming galaxies at redshifts z > or = 10. Once removed, the cusp cannot be reintroduced during the subsequent mergers involved in the build-up of larger galaxies. As a consequence, in the present Universe both small and large galaxies would have flat dark matter core density profiles, in agreement with observations. 相似文献
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Denis P. Opr Sergey V. Gnedenkov Sergey L. Sinebryukhov Elena I. Voit Alexander A. Sokolov Alexander Yu. Ustinov Veniamin V. Zheleznov 《自然科学进展(英文版)》2018,28(5):542-547
Zr~(4+) and F~– co-doped TiO_2 with the formula of Ti_(0.97)Zr_(0.03)O_(1.98)F_(0.02) was facilely synthesized by a sol-gel template route.The crystal structure,morphology,composition,surface area,and conductivity were characterized by Raman spectroscopy,energy-dispersive X-ray analysis,scanning electron microscopy,Brunauer-Emmett-Teller measurements,X-ray photoelectron spectroscopy,and electrochemical impedance spectroscopy.The results demonstrate that Zr~(4+)and F~–homogeneously incorporated into TiO_2,forming solid solution with an anatase structure.Ti_(0.97)Zr_(0.03)O_(1.98)F_(0.02)shows outstanding electrochemical properties as Li-ion battery anode in comparison with Ti_(0.97)Zr_(0.03)O_2.In particular,upon 35-fold cycling at 1C-rate Zr~(4+)/F~–co-doped TiO_2delivers a reversible capacity of 163 mAh g~(–1),whereas Zr~(4+)-doped TiO_2gives only 34 mA h g~(–1).Additionally,Zr~(4+)/F~–co-doped TiO_2retains a capacity of 138 mA h g~(–1)during cycling even at 10 C.The enhance performance originates from improved conductivity of Zr~(4+)/F~–co-doped TiO_2material through generation of Ti~(3+)(serving as electron donors)into the crystal lattice and,possibly,due to F-doping blocked the anode surface from attack of HF formed as electrolyte decomposition product. 相似文献
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Mailman MD Feolo M Jin Y Kimura M Tryka K Bagoutdinov R Hao L Kiang A Paschall J Phan L Popova N Pretel S Ziyabari L Lee M Shao Y Wang ZY Sirotkin K Ward M Kholodov M Zbicz K Beck J Kimelman M Shevelev S Preuss D Yaschenko E Graeff A Ostell J Sherry ST 《Nature genetics》2007,39(10):1181-1186
The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data. 相似文献