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91.
92.
Li J DeMello KM Cheng H Sakya SM Bronk BS Rafka RJ Jaynes BH Ziegler CB Kilroy C Mann DW Nimz EL Lynch MP Haven ML Kolosko NL Minich ML Li C Dutra JK Rast B Crosson RM Morton BJ Kirk GW Callaghan KM Koss DA Shavnya A Lund LA Seibel SB Petras CF Silvia A 《Bioorganic & medicinal chemistry letters》2004,14(1):95-98
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted. 相似文献
93.
Helal CJ Sanner MA Cooper CB Gant T Adam M Lucas JC Kang Z Kupchinsky S Ahlijanian MK Tate B Menniti FS Kelly K Peterson M 《Bioorganic & medicinal chemistry letters》2004,14(22):5521-5525
High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC(50)=ca. 320nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved. 相似文献
94.
95.
Amy?Y.?RossmanEmail author M.?Cathie Aime David?F.?Farr Lisa?A.?Castlebury Kristin?R.?Peterson Robert?Leahy 《Mycological Progress》2004,3(4):275-290
The coelomycetous genera Chaetomella and Pilidium were determined to be closely related to each other, yet are recognized as distinct genera based on both morphological observations
and rDNA sequence analyses. Analyses of the SSU and LSU of the nuclear ribosomal RNA genes suggest that Chaetomella and Pilidium along with Sphaerographium tenuirostrum and Synchaetomella lunatospora constitute a distinct lineage within the ascomycetes that is allied with the Leotiomycetes. Chaetomella and Pilidium both produce black pycnidia generally opening by a raphe, acropleurogenous conidiogenous cells, and non-septate, hyaline,
usually fusiform to falcate, rarely ellipsoid, conidia. Pycnidia of Pilidium are smooth while those of Chaetomella have setae of various types. A Hainesia sporodochial synanamorph was observed in cultures of C. oblonga and C. raphigera similar to H. lythri, the synanamorph of P. concavum. Specimens of C. oblonga, type species of Chaetomella, C. acutiseta, C. circinoseta, C. raphigera, Pilidium acerinum, type species of Pilidium, and P. concavum were examined. Diagnoses and illustrations are provided for these species along with a key to the accepted species in both
genera.
Mention of trade names or commercial products in this article is solely for the purpose of providing specific information
and does not imply recommendation or endorsement by the U.S. Department of Agriculture. 相似文献
96.
De Preter K Pattyn F Berx G Strumane K Menten B Van Roy F De Paepe A Speleman F Vandesompele J 《BMC genomics》2004,5(1):11-14
Background
Activation of proto-oncogenes by DNA amplification is an important mechanism in the development and maintenance of cancer cells. Until recently, identification of the targeted genes relied on labour intensive and time consuming positional cloning methods. In this study, we outline a straightforward and efficient strategy for fast and comprehensive cloning of amplified and overexpressed genes. 相似文献97.
The peptides (AG)(6)(VPGVG)(AG)(7) and (AG)(5)(VPGVG)(2)(AG)(5) are models for a new type of protein with both composition and properties such as Bombyx mori silk and elastin. In this paper, we report the solid-state NMR results for these samples and related peptides; the structures after dialysis of the 9 M LiBr aqueous solution and after treatment with formic acid were determined and compared. The detailed structural analyses were performed using deconvolution subroutines assuming Gaussian line shapes for the Ala Cbeta peaks of the (AG)(n) sequences in these peptides. The peptide (AG)(6)(VPGVG)(AG)(7) took the silk II structure after the dialysis, which is in contrast to the silk I form of (AG)(15) after the same treatment. However, a drastic structural change of the (AG)(n) sequences was observed for (AG)(5)(VPGVG)(2)(AG)(5); the fraction of distorted beta-turn was 81% after the dialysis, but the distorted beta-sheet became dominant (84%) after treatment with formic acid. The local structures of the Gly residue of the VG units in the elastin-like subunits, (VPGVG) and (VPGVG)(2), were the distorted structures with a distribution of the torsion angles, which was derived from the 2D spin diffusion NMR spectral pattern of (AG)(5)VPG[1-(13)C]V[1-(13)C]GVPGVG(AG)(5). Observation of this distribution of the Gly residue was independent of the treatment, dialysis or formic acid. 相似文献
98.
The functions of Klarsicht and nuclear lamin in developmentally regulated nuclear migrations of photoreceptor cells in the Drosophila eye 下载免费PDF全文
Patterson K Molofsky AB Robinson C Acosta S Cater C Fischer JA 《Molecular biology of the cell》2004,15(2):600-610
Photoreceptor nuclei in the Drosophila eye undergo developmentally regulated migrations. Nuclear migration is known to require the perinuclear protein Klarsicht, but the function of Klarsicht has been obscure. Here, we show that Klarsicht is required for connecting the microtubule organizing center (MTOC) to the nucleus. In addition, in a genetic screen for klarsicht-interacting genes, we identified Lam Dm(0), which encodes nuclear lamin. We find that, like Klarsicht, lamin is required for photoreceptor nuclear migration and for nuclear attachment to the MTOC. Moreover, perinuclear localization of Klarsicht requires lamin. We propose that nuclear migration requires linkage of the MTOC to the nucleus through an interaction between microtubules, Klarsicht, and lamin. The Klarsicht/lamin interaction provides a framework for understanding the mechanistic basis of human laminopathies. 相似文献
99.
Caccone A Gentile G Burns CE Sezzi E Bergman W Ruelle M Saltonstall K Powell JR 《Molecular phylogenetics and evolution》2004,31(2):794-798
We sequenced approximately 4.5 kb of mtDNA from 161 individuals representing 11 named taxa of giant Galápagos tortoises (Geochelone nigra) and about 4 kb of non-coding nuclear DNA from fewer individuals of these same 11 taxa. In comparing mtDNA and nucDNA divergences, only silent substitutions (introns, ITS, mtDNA control region, and synonymous substitutions in coding sequences) were considered. mtDNA divergence was about 30 times greater than that for nucDNA. This rate discrepancy for mtDNA and nucDNA is the greatest yet documented and is particularly surprising for large ectothermic animals that are thought to have relatively low rates of mtDNA evolution. This observation may be due to the somewhat unusual reproductive biology and biogeographic history of these organisms. The implication is that the ratio of effective population size of nucDNA/mtDNA is much greater than the usually assumed four. The nearly neutral theory of molecular evolution predicts this would lead to a greater difference between rates of evolution. 相似文献
100.
BACKGROUND: Neurons in primary auditory cortex are known to be sensitive to the locations of sounds in space, but the reference frame for this spatial sensitivity has not been investigated. Conventional wisdom holds that the auditory and visual pathways employ different reference frames, with the auditory pathway using a head-centered reference frame and the visual pathway using an eye-centered reference frame. Reconciling these discrepant reference frames is therefore a critical component of multisensory integration. RESULTS: We tested the reference frame of neurons in the auditory cortex of primates trained to fixate visual stimuli at different orbital positions. We found that eye position altered the activity of about one third of the neurons in this region (35 of 113, or 31%). Eye position affected not only the responses to sounds (26 of 113, or 23%), but also the spontaneous activity (14 of 113, or 12%). Such effects were also evident when monkeys moved their eyes freely in the dark. Eye position and sound location interacted to produce a representation for auditory space that was neither head- nor eye-centered in reference frame. CONCLUSIONS: Taken together with emerging results in both visual and other auditory areas, these findings suggest that neurons whose responses reflect complex interactions between stimulus position and eye position set the stage for the eventual convergence of auditory and visual information. 相似文献