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排序方式: 共有1795条查询结果,搜索用时 15 毫秒
991.
Ly Le Eric H. Lee David J. Hardy Thanh N. Truong Klaus Schulten 《PLoS computational biology》2010,6(9)
Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, as well as graphics processing unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 “avian” and H1N1pdm “swine” flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumvent the resistance mechanisms. 相似文献
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994.
Kettner C Field D Sansone SA Taylor C Aerts J Binns N Blake A Britten CM de Marco A Fostel J Gaudet P González-Beltrán A Hardy N Hellemans J Hermjakob H Juty N Leebens-Mack J Maguire E Neumann S Orchard S Parkinson H Piel W Ranganathan S Rocca-Serra P Santarsiero A Shotton D Sterk P Untergasser A Whetzel PL 《Standards in genomic sciences》2010,3(3):259-266
995.
Shayu Deshpande Valter Agosti Katia Manova Malcolm A.S. Moore Matthew P. Hardy Peter Besmer 《Developmental biology》2010,337(2):199-286
Juxtamembrane signaling via the membrane growth factor KitL is critical for Kit mediated functions. KitL has a conserved cytoplasmic domain and has been shown to possess a monomeric leucine-dependent basolateral targeting signal. To investigate the consequences in vivo of impaired basolateral KitL targeting in polarized epithelial cells, we have mutated this critical leucine to alanine using a knock-in strategy. KitLL263A/L263A mutant mice are pigmented normally and steady-state hematopoiesis is unaffected although peritoneal and skin mast cell numbers are significantly increased. KitL localization is affected in the Sertoli cells of the KitLL263A/L263A testis and testis size is reduced in these mice due to aberrant spermatogonial proliferation. Furthermore, the effect of the KitL L263A mutation on the testicular phenotype is dosage dependent. The tubules of hemizygous KitLL263A/Sl mice completely lack germ cells in contrast to the weaker testicular phenotype of KitLL263A/L263A mice. The onset of the testis phenotype coincides with the formation of tight junctions between Sertoli cells during postnatal development. Thus, the altered sorting of KitL is dispensable for hematopoietic and melanogenic lineages, yet is crucial in the testicular environment, where the basal membranes of adjacent polarized Sertoli cells form a niche for the proliferating spermatogonia. 相似文献
996.
Karen Colwill Clark D Wells Kelly Elder Marilyn Goudreault Kadija Hersi Sarang Kulkarni W Rod Hardy Tony Pawson Gregg B Morin 《BMC biotechnology》2006,6(1):13-15
Background
Recombinational systems have been developed to rapidly shuttle Open Reading Frames (ORFs) into multiple expression vectors in order to analyze the large number of cDNAs available in the post-genomic era. In the Creator system, an ORF introduced into a donor vector can be transferred with Cre recombinase to a library of acceptor vectors optimized for different applications. Usability of the Creator system is impacted by the ability to easily manipulate DNA, the number of acceptor vectors for downstream applications, and the level of protein expression from Creator vectors. 相似文献997.
998.
The biofilm-forming fungus, Aureobasidium pullulans DSM 2404, was grown in a bead-packed reactor. Alterations within the reactor were analysed in several cross-sectional slices by magnetic resonance imaging (MRI) with flow contrast. For the first time, biofilm accumulation could be continuously elucidated without using any contrast agents, and the non-stationary flow through the fixed-bed reactor could be visualized. The results indicate that the non-stationary flow through the biofilm reactor changes significantly due to the changing reactor morphology. Preferential flow lines arise during biofilm formation. The accumulation of the biomass was determined and compared to gravimetrical biomass data. The described technique can be used to monitor hydrodynamic transport, and to combine flow-field characteristics with morphological data for the prediction of undesirable reactor processes, e.g. clogging. 相似文献
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Amyloid at the blood vessel wall 总被引:5,自引:0,他引:5