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Buzard D Han S Thoresen L Moody J Lopez L Kawasaki A Schrader T Sage C Gao Y Edwards J Barden J Thatte J Fu L Solomon M Liu L Al-Shamma H Gatlin J Le M Xing C Espinola S Jones RM 《Bioorganic & medicinal chemistry letters》2011,21(19):6013-6018
S1P(1) receptor driven lymphopenia has proven utility in the treatment of an array of autoimmune disease states. As a part of our efforts to develop potent and selective S1P(1) receptor agonists, we have identified a novel chemical series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid S1P(1) receptor agonists. 相似文献
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A change in twist of actin provides the force for the extension of the acrosomal process in limulus sperm: the false-discharge reaction 总被引:1,自引:5,他引:1 下载免费PDF全文
One of the most spectacular motions is the generation of the acrosomal process in the limulus sperm. On contact with the egg, the sperm generates a 60-mum-long process that literally drills its way through the jelly surrounding the egg. This irresversible reaction takes only a few seconds. We suggested earlier that this motion is driven by a change in twist of the actin filaments comprising the acrosomal process. In this paper we analyze the so-called false discharge, a reversible reaction, in which the acrosomal filament bundle extends laterally from the base of the sperm and not anteriorly from the apex. Unlike the true discharge, which is straight, the false discharge is helical. Before extension, the filament bundle is coiled about the base of the sperm. In the coil, the bundle is not smoothly bent but consists of arms (straight segments) and elbows (corners) so that the coil looks like a 14-sided polygon. The extension of the false discharge works as follows: starting at the base of the bundle, the filaments change their twist which concomitantly changes the orientations of the elbows relative to each other; that is, in the coil, the elbows all like in a common plane, but after the change in twist, the plane of each elbow is rotated to be perpendicular to that of its neighbors. This change transforms the bundle from a compact coil into an extended left- handed helix. Because the basal end of the bundle is unconstrained, the extension is lateral. The true discharge works the same way but starts at the apical end of the bundle. The apical end, however, is constrained by its passage through the nuclear canal, which directs the extention anteriorly. Unlike the false discharge, during the true discharge the elbows are melted out, making the reaction irreversible. This study shows that rapid movement can be regenerated by actin without myosin and gives us insight into the molecular mechanism. 相似文献
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A dictionary of transcription control sequences 总被引:14,自引:0,他引:14
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Schofield DJ Pope AR Clementel V Buckell J Chapple SDj Clarke KF Conquer JS Crofts AM Crowther SR Dyson MR Flack G Griffin GJ Hooks Y Howat WJ Kolb-Kokocinski A Kunze S Martin CD Maslen GL Mitchell JN O'Sullivan M Perera RL Roake W Shadbolt SP Vincent KJ Warford A Wilson WE Xie J Young JL McCafferty J 《Genome biology》2007,8(11):R254-18
We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation. 相似文献
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