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31.
Jordan Rosenfeld Marc Porter Mike Pearson Beverly Wicks Pier van Dishoeck Tyese Patton Eric Parkinson Gordon Haas Don McPhail 《Environmental Biology of Fishes》2001,62(4):401-413
We intensively sampled fish in rivers and streams within a single major drainage basin (the Blackwater River) and across major drainages in British Columbia to assess the factors influencing distribution of chiselmouth, Acrocheilus alutaceus, and to develop models for predicting chislemouth presence. Chiselmouth were typically absent from sites with maximum temperatures below 20°C or 2100 annual degree days, both within a single drainage and between larger drainages. Indices of stream size (bankfull channel width and basin area) were the most significant predictors of chiselmouth presence within the Blackwater drainage (p=0.016 and p=0.032, respectively), and inclusion of thermal variables only marginally increased classification success. In contrast, bankfull channel width and basin area were poor predictors of chiselmouth presence in mainstem habitat within larger drainage basins throughout British Columbia. Inclusion of thermal variables (particularly degree days > 12°C) doubled correct classification rates of chiselmouth presence across larger drainage basins. These habitat associations suggest that water temperature is the primary constraint on presence of chiselmouth populations in larger drainages across a landscape, while selection of different habitat types (mainstem habitat over smaller tributaries) determines distribution within any given basin. 相似文献
32.
33.
Cooke A Anderson A Buchanan K Byford A Gemmell D Hamilton N McPhail P Miller S Sundaram H Vijn P 《Bioorganic & medicinal chemistry letters》2001,11(7):927-930
Propofol (2,6-diisopropylphenol) is a widely used intravenous anaesthetic that is formulated as an emulsion since it lacks water solubility. We report a range of water-soluble analogues of propofol, containing a para-alkylamino substituent, which retain good intravenous anaesthetic activity in rodents. 相似文献
34.
Han S Hamel E Bastow KF McPhail AT Brossi A Lee KH 《Bioorganic & medicinal chemistry letters》2002,12(20):2851-2853
N-Acetylcolchinol methyl ether 1 served as the starting material to prepare the chloroacetamide (3) and epoxide (5) analogues. Both 3 and 5 were potent inhibitors of tubulin polymerization in vitro. Compound 3 was also 4-fold more cytotoxic than colchicine against the 1A9 tumor cell line and showed a unique cross-resistance profile. 相似文献
35.
Synthesis and NK(1)/NK(2) binding activities of a series of diacyl-substituted 2-arylpiperazines 总被引:1,自引:0,他引:1
Blythin DJ Chen X Piwinski JJ Shih NY Shue HJ Anthes JC McPhail AT 《Bioorganic & medicinal chemistry letters》2002,12(21):3161-3165
The synthesis and binding affinity for hNK(1) and hNK(2) receptors of a series of diacyl substituted 2-aryl piperazines are described. SAR evaluation led to the racemic derivative 11g as an apparent dual inhibitor. Chiral chromatographic separation of 11g led to the observation that NK(1) activity was shown by one enantiomer (13a) and NK(2) activity was shown by the other enantiomer (13b). X-ray crystallographic analysis of the crystalline di-BOC derivative of the NK(2) active piperazine (15) showed that the 2R configuration was associated with NK(2) activity. Further derivatization indicated that dual NK(1)/NK(2) activity could be built into the 2R series. 相似文献
36.
37.
A common polygenic basis for quinine and PROP avoidance in mice 总被引:1,自引:2,他引:1
Inbred strains of mice (Mus musculus) differ greatly in ability to taste
various bitter compounds. For some compounds, the differences result from
allelic variation at a single locus. However, segregation patterns
incompatible with monogenic inheritance have been found for quinine
avoidance. The Soa bitter sensitivity locus exerts some influence on this
phenotype, but an unknown number of other loci also contribute. Relative
avoidance patterns for quinine sulfate in panels of naive inbred strains
resembled avoidance patterns for 6-n-propyl-2- thiouracil (PROP),
suggesting a common genetic basis. In particular, C57BL/6J mice strongly
avoided both 0.1 mM quinine sulfate and 1 mM PROP in two-bottle preference
tests, whereas C3H/HeJ mice were indifferent to both. Therefore, 12 BXH/Ty
recombinant inbred strains, derived from these strains, were tested with
both solutions to begin identification of the unknown bitter loci. Naive
mice were tested for four consecutive days with each compound (order
counterbalanced). Some BXH/Ty strain means resembled those of the parent
strains, but others were intermediate. This indicated recombination among
loci affecting avoidance, and therefore polygenic inheritance. The strain
means were highly correlated across compounds (r = 0.98), suggesting that
the same polygenes controlled both phenotypes. The BXH/Ty means for both
compounds were then compared with the strain genotypes at 212 chromosome
position markers distributed throughout the genome. Eight markers on five
chromosomes (3, 6, 7, 8 and 9) yielded significant correlations. Six of the
markers were correlated with both phenotypes, again suggesting common
polygenic inheritance. The marker with the highest correlation was Prp,
tightly linked to Soa on chromosome 6. The correlated marker regions likely
contain quantitative trait loci affecting bitter avoidance. The phenotypic
similarity of PROP to quinine, rather than to phenylthiourea, apparently
stemming from a common polygenic basis, indicates a difference between mice
and humans in gustatory organization related to bitters.
相似文献
38.
I Tabas L L Chen J W Clader A T McPhail D A Burnett P Bartner P R Das B N Pramanik M S Puar S J Feinmark 《The Journal of biological chemistry》1990,265(14):8042-8051
Acyl-coenzyme A (CoA):cholesterol acyltransferase (ACAT) catalyzes the intracellular fatty acid esterification of cholesterol and is thought to play a key role in lipoprotein metabolism and atherogenesis. Herein we describe the purification and characterization of a novel pentacyclic triterpene ester from rabbit liver that has ACAT inhibitory activity. The inhibitor was purified by a combination of silicic acid chromatography and preparative thin layer chromatography. The compound inhibited both rabbit and rat liver microsomal ACAT activity with an IC50 = 20 microM. The lipid did not inhibit fatty acid incorporation into triglycerides, diglycerides, monoglycerides, or phospholipids nor did it inhibit plasma lecithin:cholesterol acyltransferase activity. However, rat liver microsomal acyl-CoA:retinol acyltransferase activity was inhibited by the terpene ester. Kinetic data are consistent with a mechanism in which ACAT is inhibited by the compound in an irreversible manner. The subcellular fractionation pattern of both ACAT activity and the ACAT inhibitor were similar in rabbit liver (both were approximately equally distributed in membranes that pelleted at 10,000 X g and 100,000 X g). A lipid with similar properties to the rabbit liver inhibitor was found in many other rabbit tissues, including adrenal and spleen, as well as in human liver. Rat liver did not contain this lipid. Structural analysis by NMR, mass spectrometry, and x-ray crystallography indicated that the rabbit liver inhibitor was a fatty acid ester (mostly stearate) of a pentacyclic triterpene acid. The carbon skeleton of the triterpene moiety is a new member of the olean-12-ene triterpene family. Both the negatively charged carboxylic acid group of the triterpene moiety and the esterified fatty acid group were necessary for the ACAT-inhibitory activity of the triterpene ester. Lastly, we present preliminary data which, together with the structural homology of the rabbit triterpene with known plant compounds, suggest the hypothesis that the triterpene moiety of the rabbit ACAT inhibitor arises from dietary absorption of a plant triterpene. 相似文献
39.
L C McPhail K A Waite D S Regier J B Nixon D Qualliotine-Mann W X Zhang R Wallin S Sergeant 《Biochimica et biophysica acta》1999,1439(2):277-290
Activation of phospholipase D occurs in response to a wide variety of hormones, growth factors, and other extracellular signals. The initial product of phospholipase D, phosphatidic acid (PA), is thought to serve a signaling function, but the intracellular targets for this lipid second messenger are not clearly identified. The production of PA in human neutrophils is closely correlated with the activation of NADPH oxidase, the enzyme responsible for the respiratory burst. We have developed a cell-free system, in which the activation of NADPH oxidase is induced by the addition of PA. Characterization of this system revealed that a multi-functional cytosolic protein kinase was a target for PA, and that two NADPH oxidase components were substrates for the enzyme. Partial purification of the PA-activated protein kinase separated the enzyme from known protein kinase targets of PA. The partially purified enzyme was selectively activated by PA, compared to other phospholipids, and phosphorylated the oxidase component p47-phox on both serine and tyrosine residues. PA-activated protein kinase activity was present in a variety of hematopoietic cells and cell lines and in rat brain, suggesting it has widespread distribution. We conclude that this protein kinase may be a novel target for the second messenger function of PA. 相似文献
40.
Claire E. Thompson Eric B. Taylor J. Donald McPhail 《Evolution; international journal of organic evolution》1997,51(6):1955-1965
Three drainage systems in British Columbia, Canada, contain divergent parapatric lake-stream pairs of threespine sticklebacks (Gasterosteus aculeatus): Drizzle and Mayer Lakes on Graham Island, Queen Charlotte Islands, and Misty Lake on northeastern Vancouver Island. Ecological and morphological differences between members of all three lake-stream pairs are strikingly similar; lake fish are melanistic and slim bodied with smaller mouths and more gill rakers than the mottled-brown and robust-bodied stream sticklebacks. We estimated the level of genetic divergence between lake and stream fish in Misty Lake and tested hypotheses of single versus multiple origins of the pairs by assaying mitochondrial DNA (mtDNA) restriction site variation in samples from the three lake systems. MtDNA analysis revealed the existence of two highly divergent lineages differing by 2.7% in sequence. One lineage predominated in Misty stream fish (73%), whereas the other lineage predominated in Misty Lake samples (96%). Comparable forms (lake or stream) in the different lakes did not cluster together in terms of mtDNA nucleotide divergence, suggesting that the pairs have had independent origins. We concluded that: (1) divergent mtDNA lineages in North Pacific sticklebacks stem from historical isolation in the two major glacial refugia proposed for the North Pacific (Beringia and Cascadia); (2) the stream and lake pair in Misty Lake are distinct gene pools; (3) the divergence between parapatric lake and stream Gasterosteus represents parallel evolution having occurred at least twice in the North Pacific; and (4) different scales of evolutionary divergence exist in North Pacific Gasterosteus, that is, a relatively ancient divergence of mtDNA clades as well as recent (i.e., postglacial) divergence of ecotypes within major clades. 相似文献