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891.
892.
893.
M A Massa D P Spangler R C Durley B S Hickory D T Connolly B J Witherbee M E Smith J A Sikorski 《Bioorganic & medicinal chemistry letters》2001,11(13):1625-1628
A series of novel N,N-disubstituted trifluoro-3-amino-2-propanols has been prepared as potent inhibitors of cholesteryl ester transfer protein (CETP). Modifying the aromatic 3-tetrafluoroethoxy group in the lead molecule 1a with various heteroaryl moieties produced new 2-furyl analogues 2a,b with submicromolar potency in vitro. 相似文献
894.
A G DiLella T J Toner C P Austin B M Connolly 《The journal of histochemistry and cytochemistry》2001,49(5):669-670
Differences between benign prostatic hyperplasia (BPH) and normal prostate tissue at the level of mRNA expression provide an opportunity to identify candidate genes for this disease. A cDNA subtraction procedure was used to isolate differentially expressed genes in BPH. The subtraction was done by solution hybridization of BPH cDNA against excess normal prostate cDNA. We identified known, EST, and novel genes by sequence and database analysis of the subtracted cDNAs. Several of these cDNAs were used as probes in Northern blotting analysis to confirm over-expression of their corresponding mRNAs in BPH tissues. One highly upregulated sequence of interest shared identity with a known mRNA encoding human NELL2, a protein containing epidermal growth factor-like domains. NELL2 was not previously reported to be expressed in prostate and may code for a novel prostatic growth factor. In situ hybridization analysis of hyperplastic prostate specimens demonstrated that NELL2 mRNA expression is predominantly localized in basal cells of the epithelium. Disease-related changes in the levels of NELL2 may contribute to alterations in epithelial-stromal homeostasis in BPH. (J Histochem Cytochem 49:669-670, 2001) 相似文献
895.
Caroline Brophy David J. Gibson Peter M. Wayne John Connolly 《Journal of Plant Ecology》2008,1(4):207
Aims We investigate the effect of position within a size-structured population on the reproductive allocation (RA) and flowering probability of individual plants of Sinapis arvensis. We also assess the effects of plant size and changing level of CO2 on both responses.Methods Sinapis arvensis L., (field mustard), an annual agricultural weed, was grown in monoculture at six densities under ambient and elevated CO2 in a study with 84 stands. Individual aboveground biomass and reproductive biomass were measured. Varying density produced a wide range of mean plant sizes across stands and size hierarchies within stands. Many (~40%) individuals had zero reproductive biomass. Employing a novel modelling approach, we analysed the joint effects of position in stand size hierarchy, plant size and CO2 on RA and flowering probability of individuals.Important findings We found a strong effect of position within the size hierarchy of individuals in a population: for an individual of a given size, greater size relative to neighbours substantially increased RA and flowering probability at a single harvest time. There was no other effect of plant size on RA. We found a positive effect of elevated CO2 on RA regardless of position within the size hierarchy. These observed patterns could impact doubly on the reproductive biomass (R) of small individuals. First, because RA is not affected by size, smaller plants will have smaller R than larger plants; and second, for smaller plants lower down in a population size hierarchy, their RA and hence R will be further reduced. These results suggest that size relative to neighbours may be independent of and more important than direct abiotic effects in determining RA. Further studies are required to evaluate how these observed patterns generalize to other populations in non-experimental conditions. 相似文献
896.
Huang S Li R Connolly PJ Xu G Gaul MD Emanuel SL Lamontagne KR Greenberger LM 《Bioorganic & medicinal chemistry letters》2006,16(23):6063-6066
A novel 4-aminopyrimidine-5-carboxaldehyde oxime scaffold with inhibitory activity against VEGFR-2 kinase has been identified. With a 4-fluoro-2-methylindol-5-yloxy group at the 6-position and alkyl groups as the oxime side chains, many analogues showed good potency for VEGFR-2. This series also exhibited antiproliferative activity against cancer cells, causing cell accumulation at the G2/M phase of the cell cycle and preventing cells from entering mitosis. Described here are the chemistry, structure-activity relationships (SAR), and biological testing for this series. 相似文献
897.
Fairbank NJ Connolly SC Mackinnon JD Wehry K Deng L Maksym GN 《American journal of physiology. Lung cellular and molecular physiology》2008,295(3):L479-L488
Chronic contractile activation, or tone, in asthma coupled with continuous stretching due to breathing may be involved in altering the contractile function of airway smooth muscle (ASM). Previously, we (11) showed that cytoskeletal remodeling and stiffening responses to acute (2 h) localized stresses were modulated by the level of contractile activation of ASM. Here, we investigated if altered contractility in response to chronic mechanical strain was dependent on repeated modulation of contractile tone. Cultured human ASM cells received 5% cyclic (0.3 Hz), predominantly uniaxial strain for 5 days, with once-daily dosing of either sham, forskolin, carbachol, or histamine to alter tone. Stiffness, contractility (KCl), and "relaxability" (forskolin) were then measured as was cell alignment, myosin light-chain phosphorylation (pMLC), and myosin light-chain kinase (MLCK) content. Cells became aligned and baseline stiffness increased with strain, but repeated lowering of tone inhibited both effects (P < 0.05). Strain also reversed a negative tone-modulation dependence of MLCK, observed in static conditions in agreement with previous reports, with strain and tone together increasing both MLCK and pMLC. Furthermore, contractility increased 176% (SE 59) with repeated tone elevation. These findings indicate that with strain, and not without, repeated tone elevation promoted contractile function through changes in cytoskeletal organization and increased contractile protein. The ability of repeated contractile activation to increase contractility, but only with mechanical stretching, suggests a novel mechanism for increased ASM contractility in asthma and for the role of continuous bronchodilator and corticosteroid therapy in reversing airway hyperresponsiveness. 相似文献
898.
899.
Willeke MC van Roon-Mom Barry A Pepers Peter AC 't Hoen Carola ACM Verwijmeren Johan T den Dunnen Josephine C Dorsman GertJan B van Ommen 《BMC molecular biology》2008,9(1):84
Background
Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease. 相似文献900.
Milano A Pendergrass SA Sargent JL George LK McCalmont TH Connolly MK Whitfield ML 《PloS one》2008,3(7):e2696