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81.
82.
Alexander RP Warrellow GJ Eaton MA Boyd EC Head JC Porter JR Brown JA Reuberson JT Hutchinson B Turner P Boyce B Barnes D Mason B Cannell A Taylor RJ Zomaya A Millican A Leonard J Morphy R Wales M Perry M Allen RA Gozzard N Hughes B Higgs G 《Bioorganic & medicinal chemistry letters》2002,12(11):1451-1456
The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig. 相似文献
83.
Hutchinson TP Gudlaugsdottir S 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2002,24(2):121-124
OBJECTIVE: To construct a statistical model for the agreements and disagreements between two observers on darkness of staining. STUDY DESIGN: Data from an earlier observer-agreement study by van Diest et al were reanalyzed. RESULTS: A model in which the random variation in error is permitted to depend upon the true darkness of staining wasfound tofit the data much better than does one in which the random variation is constant. CONCLUSION: For the dataset analyzed, error tends to be greater (that is, correlation between observers tends to be less) when staining is darker. 相似文献
84.
Aojula HS Offerman S Aojula RR Hutchinson AP Nicklin S Clarke DJ 《Biochimica et biophysica acta》2002,1564(1):73-81
Potent cytolytic peptides with specific tethering and cloaking sites have been synthesised and used to release payload from liposomes in a quantitative manner. A functionally located cloaking site has been modified specifically by simple conjugation without adversely affecting the cytolytic properties of the peptide. The cytolytic activity of modified peptides was then efficiently (>98%) cloaked and uncloaked by ligand-protein or hapten-antibody interactions. The principle of a dual response peptide has been demonstrated using an avidin-cloaked pH-sensitive peptide. Biospecific cloaking/uncloaking provided a new sensitive (approximately 12 pmol) homogeneous diagnostic and also appears potentially suited to bioresponsively targeted release of antimicrobial, anticancer and other drugs now delivered using liposomes. 相似文献
85.
Approaches to stabilization of inter-domain recombination in polyketide synthase gene expression plasmids 总被引:1,自引:0,他引:1
Hu Z Desai RP Volchegursky Y Leaf T Woo E Licari P Santi DV Hutchinson CR McDaniel R 《Journal of industrial microbiology & biotechnology》2003,30(3):161-167
Regions of extremely high sequence identity are recurrent in modular polyketide synthase (PKS) genes. Such sequences are
potentially detrimental to the stability of PKS expression plasmids used in the combinatorial biosynthesis of polyketide metabolites.
We present two different solutions for circumventing intra-plasmid recombination within the megalomicin PKS genes in Streptomyces coelicolor. In one example, a synthetic gene was used in which the codon usage was reengineered without affecting the primary amino
acid sequence. The other approach utilized a heterologous subunit complementation strategy to replace one of the problematic
regions. Both methods resulted in PKS complexes capable of 6-deoxyerythronolide B analogue biosynthesis in S. coelicolor CH999, permitting reproducible scale-up to at least 5-l stirred-tank fermentation and a comparison of diketide precursor
incorporation efficiencies between the erythromycin and megalomicin PKSs.
Electronic Publication 相似文献
86.
Hall MJ Hutchinson RA Farkas R Adams ZJ Wyatt NP 《Medical and veterinary entomology》2003,17(3):280-287
The Lucitrap (Miazma Pty Ltd, Queensland, Australia) combined with a synthetic odour bait, Lucilure (Miazma Pty Ltd, Queensland, Australia), is a commercially available trap for sampling and control of Lucilia cuprina (Wiedemann) in Australia. It was tested in Hungary against Lucilia sericata (Meigen) (Diptera: Calliphoridae), a cause of sheep strike throughout temperate Europe. The standard Lucitrap was tested against black or yellow sticky target traps. Both trap types were baited with either Lucilure or liver and 10% w/v sodium sulphide solution. With Lucilure as bait, L. sericata were caught on sticky traps but not in Lucitraps. With liver and sodium sulphide as bait, sticky traps caught 500-1500 times more L. sericata than Lucitraps. An adhesive sheet fitted to the top of a Lucitrap captured 30-300 times more L. sericata then were captured inside an unaltered Lucitrap. Direct observation of metallic green calliphorids (92.1% L. sericata) alighting on Lucitraps indicated that most flies stayed for a short while (modal class 2-4 s) and only a few stayed longer, to an observed maximum of 28 s. Flies explored a mean of 1.5 entry holes (range 0-7) during a visit but only 6% entered the trap. Size of L. sericata was not a physical barrier to Lucitrap entry, because many larger species were captured. However, L. sericata captured inside Lucitraps were significantly smaller than those captured on sticky traps, demonstrating that size was of behavioural importance. The data demonstrate that the Lucitrap is not effective as a trap for L. sericata in Hungary, due mainly to a failure of flies to enter the trap in large numbers. In Australia and South Africa, L. sericata is commonly caught in Lucitraps baited with Lucilure, although L. cuprina is more numerous. Our study highlights the potential for diversity of fly behaviour between different geographical populations of the same species. Such diversity can have a significant effect on the functioning of systems for fly sampling and control, when these systems depend for their success on certain behavioural responses of the target species. 相似文献
87.
Breslin MJ Duggan ME Halczenko W Fernandez-Metzler C Hunt CA Leu CT Merkle KM Naylor-Olsen AM Prueksaritanont T Stump G Wallace A Rodan SB Hutchinson JH 《Bioorganic & medicinal chemistry letters》2003,13(10):1809-1812
Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties. 相似文献
88.
To investigate the persistence of flea larvicidal activity in the immediate environment of cats treated with imidacloprid, eggs of the cat flea Ctenocephalides felis felis Bouché (Siphonaptera: Pulicidae), from untreated donor cats, were incubated on samples of fleece blanket taken from the floor of cages used by treated or untreated cats for a total of 10 or 20 6-h periods over 2-4 weeks, respectively. Sufficient imidacloprid accumulated during these periods to reduce the emergence of adult fleas by 94.7-97.6% when the blankets were tested after 18 weeks' storage at room temperature. A typical laundry procedure (washing with detergent at 50 degrees C and low temperature tumble drying) removed this biological activity. Unwashed control blankets did not support the flea life-cycle as effectively as washed blankets or a sand substrate. 相似文献
89.
The structure of the nasal chemosensory system in squamate reptiles. 1. The olfactory organ,with special reference to olfaction in geckos 总被引:1,自引:0,他引:1
The luminal surface of the chemosensory epithelia of the main olfactory organ of terrestrial vertebrates is covered by a layer of fluid. The source of this fluid layer varies among vertebrates. Little is known regarding the relative development of the sources of fluid (sustentacular cells and Bowman's glands) in reptiles, especially in gekkotan lizards (despite recent assertions of olfactory speciality). This study examined the extent and morphology of the main olfactory organ in several Australian squamate reptiles, including three species of gekkotans, two species of skinks and one snake species. The olfactory mucosa of two gekkotan species (Christinus marmoratus and Strophurus intermedius) is spread over a large area of the nasal cavity. Additionally, the sustentacular cells of all three gekkotan species contained a comparatively reduced number of secretory granules, in relation to the skinks or snake examined. These observations imply that the gekkotan olfactory system may function differently from that of either skinks or snakes. Similar variation in secretory granule abundance was previously noted between mammalian and non-mammalian olfactory sustentacular cells. The observations in gekkotans suggests that the secretory capacity of the non-mammalian olfactory sustentacular cells show far more variation than initially thought. 相似文献
90.
Guanine nucleotide dissociation stimulator (GDS) promotes the release of tightly bound GDP from various Ras superfamily proteins, including RhoA, Rac1, K-Ras, Rap1A, and Rap1B. It displays no significant sequence homology to other known exchange factors for small G-proteins. Studies are reported here of the mechanism of GDS-mediated nucleotide release from RhoA using a combination of equilibrium and stopped-flow kinetic measurements, employing fluorescent N-methylanthraniloyl (mant) derivatives of GDP and 2'-deoxyGDP. It is proposed that GDS operates by an associative displacement mechanism where stimulated nucleotide release from the Rho.mantGDP complex occurs via a transiently populated ternary complex (Rho.GDS.mantGDP). In kinetic experiments where excess GDS was mixed with the Rho.mantGDP complex, stimulated mantGDP dissociation rates of 1 s(-)(1) were measured during a single turnover, representing a 5000-fold enhancement over the intrinsic rate of mantGDP dissociation from Rho. The stable, nucleotide-free binary complex Rho.GDS was isolated. When the Rho.GDS complex was mixed with excess mantGDP, a biphasic increase in fluorescence occurred, the observed rate constants of which both reached saturating values at high mantGDP concentrations. This is compelling evidence that an isomerization of the Rho.GDS.mantGDP ternary complex is an important feature of the mechanism of nucleotide release. 相似文献