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41.
Bennett DJ Anderson A Buchanan K Byford A Cooke A Gemmell DK Hamilton NM Maidment MS McPhail P Stevenson DF Sundaram H Vijn P 《Bioorganic & medicinal chemistry letters》2003,13(12):1971-1975
A number of water soluble bis-amino-2,6-dimethoxyphenyl ester derivatives were found to exhibit improved anaesthetic activity in mice relative to propofol 1. Of the analogues disclosed, 44 was further profiled in rodents and found to be a superior agent to propofol for the induction and maintenance of anaesthesia. 相似文献
42.
Adaptive divergence and the balance between selection and gene flow: lake and stream stickleback in the Misty system 总被引:4,自引:0,他引:4
Hendry AP Taylor EB McPhail JD 《Evolution; international journal of organic evolution》2002,56(6):1199-1216
We investigated the interplay between natural selection and gene flow in the adaptive divergence of threespine stickleback (Gasterosteus aculeatus) that reside parapatrically in lakes and streams. Within the Misty Lake system (Vancouver Island, British Columbia), stickleback from the inlet stream (flowing into the lake) have fewer gill rakers and deeper bodies than stickleback from the lake--differences thought to facilitate foraging (benthic macroinvertebrates in the stream vs. zooplankton in the open water of the lake). Common-garden experiments demonstrated that these differences have a genetic basis. Reciprocal transplant enclosure experiments showed that lake and inlet stickleback grow best in their home environments (although differences were subtle and often not significant). Release-recapture experiments in the inlet showed that lake fish are less well-suited than inlet fish for life in the stream (higher mortality or emigration in lake fish). Morphological divergence in the wild and under common rearing was greater between the lake and the inlet than between the lake and the outlet. Genetic divergence (mitochondrial DNA and microsatellites) was greatest between the lake and the upper inlet (1.8 km upstream from the lake), intermediate between the lake and the lower inlet (0.9 km upstream), and least between the lake and the outlet stream (1.2 km downstream). Relative levels of gene flow estimated from genetic data showed the inverse pattern. The negative association between morphological divergence and gene flow is consistent with the expectation that gene flow can constrain adaptation. Estimated absolute levels of gene flow also implied a constraint on adaptation in the outlet but not the inlet. Our results suggest that natural selection promotes the adaptive divergence of lake and stream stickleback. but that the magnitude of divergence can be constrained by gene flow. 相似文献
43.
44.
Jain RK; Piskorz CF; Huang BG; Locke RD; Han HL; Koenig A; Varki A; Matta KL 《Glycobiology》1998,8(7):707-717
The selectins interact in important normal and pathological situations with
certain sialylated, fucosylated glycoconjugate ligands containing sialyl
Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone
into the synthesis of sialylated and sulfated Lewisxanalogs as competitive
ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and
PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure,
we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++
+-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L
and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies
have shown that sulfate esters can replace sialic acid in some selectin
ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. ,
Nature, 361, 555, 1993). Based upon these observations, we hypothesized
that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of
interacting with L- and P-selectin. To examine this hypothesis, we
synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++
+-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better
than sialyl Lexfor P and L selectin, respectively. We also report the
synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1-
3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to
be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe.
Combining this with our knowledge of Core 2 branched structures, we have
synthesized a molecule that is 5- to 6-fold better at inhibiting L- and
P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures,
substitution of a sulfate ester group for a sialic acid residue in such a
molecule resulted in a considerable loss of inhibition ability. Thus, the
combination of a sialic acid residue on the primary (beta1-3) arm, and a
modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2
structure generated a monovalent synthetic oliogosaccharide inhibitor
superior to SLexfor both L- and P-selectin.
相似文献
45.
Donald B. McPhail Philip C. Morrice Garry G. Duthie J. V. Bannister 《Free radical research》1993,18(3):177-181
Finnish Landrace sheep with a genetic lesion which results in restricted cysteine transport across the red cell membrane have total glutathione concentrations in their red blood cells that are approximately 40% of those in normal sheep of the same breed. However, dimethyldisulphide-challenged red blood cells from both phenotypes produce an ESR-spin adduct at similar rates. The resistance of the low glutathione phenotype red cells to oxidant challenge is reflected by increases in the activities of antioxidant enzymes. Sheep with a genotypic disorder in cysteine transport may be a suitable model for studying the genetic expression of antioxidant enzymes in response to oxidant loads. 相似文献
46.
47.
Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro
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The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (ρO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; ρO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it. 相似文献
48.
49.
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
50.
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