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991.
Komalavilas P Penn RB Flynn CR Thresher J Lopes LB Furnish EJ Guo M Pallero MA Murphy-Ullrich JE Brophy CM 《American journal of physiology. Lung cellular and molecular physiology》2008,294(1):L69-L78
Activation of the cAMP/cAMP-dependent PKA pathway leads to relaxation of airway smooth muscle (ASM). The purpose of this study was to examine the role of the small heat shock-related protein HSP20 in mediating PKA-dependent ASM relaxation. Human ASM cells were engineered to constitutively express a green fluorescent protein-PKA inhibitory fusion protein (PKI-GFP) or GFP alone. Activation of the cAMP-dependent signaling pathways by isoproterenol (ISO) or forskolin led to increases in the phosphorylation of HSP20 in GFP but not PKI-GFP cells. Forskolin treatment in GFP but not PKI-GFP cells led to a loss of central actin stress fibers and decreases in the number of focal adhesion complexes. This loss of stress fibers was associated with dephosphorylation of the actin-depolymerizing protein cofilin in GFP but not PKI-GFP cells. To confirm that phosphorylated HSP20 plays a role in PKA-induced ASM relaxation, intact strips of bovine ASM were precontracted with serotonin followed by ISO. Activation of the PKA pathway led to relaxation of bovine ASM, which was associated with phosphorylation of HSP20 and dephosphorylation of cofilin. Finally, treatment with phosphopeptide mimetics of HSP20 possessing a protein transduction domain partially relaxed precontracted bovine ASM strips. In summary, ISO-induced phosphorylation of HSP20 or synthetic phosphopeptide analogs of HSP20 decreases phosphorylation of cofilin and disrupts actin in ASM, suggesting that one possible mechanism by which HSP20 mediates ASM relaxation is via regulation of actin filament dynamics. 相似文献
992.
Sunday Adekunle Adebusoye Flynn W. Picardal Matthew O. Ilori Olukayode O. Amund 《World journal of microbiology & biotechnology》2008,24(7):1203-1208
The biodegradation of polychlorinated biphenyls (PCBs) by diverse bacteria including those utilized in this study is often
incomplete, a concomitant accumulation of chlorobenzoic acids (CBAs) are released as dead-end products. The build-up of these
metabolites in the growth medium may result in feed-back inhibition and impede PCB biotransformation. In this investigation
using GC-ECD and HPLC analyses, we confirmed that CBAs inhibit growth and PCB biodegradation potentials of five tropical bacteria
namely, Pseudomonas aeruginosa SA-1, Enterobacter sp. SA-2, Ralstonia sp. SA-3, Ralstonia sp. SA-5 and Pseudomonas sp. SA-6. Among the four CBAs (2-CBA, 3-CBA, 4-CBA acids and 2,3-diCBA), 3-CBA was the strongest inhibitor followed by 4-CBA.
Furthermore, we found that 3-CBA heavily inhibited growth of SA-3 and SA-6 on monochlorobiphenyls by 82–90% while elimination
rate was inhibited by 71–88%. In the case of 2,3-diCBA, inhibition was generally less than 60%. However, effects of both acids
were stronger in SA-3 than SA-6. We also found that 3-CBA and 2,3-diCBA completely inhibited carbon-chloride cleavage of 2-CB
and 3-CB since cultivation in the absence of the acids resulted in recovery of 23–50% chloride in the culture fluids of organisms.
These findings may therefore, have practical and ecological significance and are useful for improving the efficiency and the
stability of some biological treatment processes. 相似文献
993.
Tucker TJ Saggar S Sisko JT Tynebor RM Williams TM Felock PJ Flynn JA Lai MT Liang Y McGaughey G Liu M Miller M Moyer G Munshi V Perlow-Poehnelt R Prasad S Sanchez R Torrent M Vacca JP Wan BL Yan Y 《Bioorganic & medicinal chemistry letters》2008,18(9):2959-2966
Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations. 相似文献
994.
Ye XY Li YX Farrelly D Flynn N Gu L Locke KT Lippy J O'Malley K Twamley C Zhang L Ryono DE Zahler R Hariharan N Cheng PT 《Bioorganic & medicinal chemistry letters》2008,18(12):3545-3550
Several series of substituted dehydropiperidine and piperidine-4-carboxylic acid analogs have been designed and synthesized as novel, potent dual PPARalpha/gamma agonists. The SAR of these series of analogs is discussed. A rare double bond migration occurred during the basic hydrolysis of the alpha,beta-unsaturated dehydropiperidine esters 12, and the structures of the migration products were confirmed through a series of 2D NMR experiments. 相似文献
995.
Flynn E 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1509):3541-3551
The primary goal of this study was to investigate cultural transmission in young children, with specific reference to the phenomenon of overimitation. Diffusion chains were used to compare the imitation of 2- and 3-year-olds on a task in which the initial child in each chain performed a series of relevant and irrelevant actions on a puzzle box in order to retrieve a reward. Children in the chains witnessed the actions performed on one of two boxes, one which was transparent and so the lack of causality of the irrelevant actions was obvious, while the other was opaque and so the lack of causal relevance was not obvious. Unlike previous dyadic research in which children overimitate a model, the irrelevant actions were parsed out early in the diffusion chains. Even though children parsed out irrelevant actions, they showed fidelity to the method used to perform a relevant action both within dyads and across groups. This was true of 3-year-olds, and also 2-year-olds, therefore extending findings from previous research. 相似文献
996.
Contaminated sites in Lagos, Nigeria were screened for the presence of chlorobiphenyl-degrading bacteria. The technique of
continual enrichment on Askarel fluid yielded bacterial isolates able to utilize dichlorobiphenyls (diCBs) as growth substrates
and six were selected for further studies. Phenotypic typing and 16S rDNA analysis classified these organisms as species of
Enterobacter, Ralstonia and Pseudomonas. All the strains readily utilized a broad spectrum of xenobiotics as sole sources of carbon and energy. Growth was observed
on all monochlorobiphenyls (CBs), 2,2′-, 2,3-, 2,4′-, 3,3′- and 3,5-diCB as well as di- and trichlorobenzenes Growth was also
sustainable on Askarel electrical transformer fluid and Aroclor 1221. Time-course studies using 100 ppm of 2-, 3- or 4-CB
resulted in rapid exponential increases in cell numbers and CB transformation to respective chlorobenzoates (CBAs) within
70 h. Significant amounts of chloride were recovered in culture media of cells incubated with 2-CB and 3-CB, suggesting susceptibilities
of both 2- and 3-chlorophenyl rings to attack, while the 4-CB was stoichiometrically transformed to 4-CBA. Extensive degradation
of most of the congeners in Aroclor 1221 was observed when isolates were cultivated with the mixture as a sole carbon source.
Aroclor 1221 was depleted by a minimum of 51% and maximum of 71%. Substantial amounts of chloride eliminated from the mixture
ranged between 15 and 43%. These results suggest that some contaminated soils in the tropics may contain exotic micro-organisms
whose abilities and potentials are previously unknown. An understanding of these novel strains therefore, may help answer
questions about the microbial degradation of polychlorinated biphenyls (PCBs) in natural systems and enhance the potential
use of bioremediation as an effective tool for cleanup of PCB-contaminated soils. 相似文献
997.
Aurelio L Figler H Flynn BL Linden J Scammells PJ 《Bioorganic & medicinal chemistry》2008,16(3):1319-1327
Two series of 5-substituted 2-amino-4-(3-trifluoromethylphenyl)thiophenes were prepared and evaluated as allosteric enhancers at the A(1) adenosine receptor (A(1)AR). In the 3-benzoyl series, a 5-phenyl group was found to confer the greatest potency (9a: ED(50)=2.1 microM, AE score=18%). However, the analogue with no 5-substituent (6b: ED(50)=15.8 microM, AE score=77%) proved to be the most efficacious. In the 3-ethoxycarbonyl series, the 5-(4-chlorophenyl) analogue was clearly the most potent and efficacious (9l: ED(50)=6.6 microM, AE score=57%). The antagonist activity of all compounds was measured using a [(3)H]CPX competitive binding assay. 相似文献
998.
Dario De Franceschi Carina Hoorn Pierre-Olivier Antoine Iqbal U. Cheema Lawrence J. Flynn Everett H. Lindsay Laurent Marivaux Grgoire Mtais A. Rahim Rajpar Jean-Loup Welcomme 《Review of Palaeobotany and Palynology》2008,150(1-4):115-129
Floral remains are generally rare in the fossil record of Pakistan. We present here new discoveries of mid-Cenozoic wood and pollen of Oligocene deposits from central Pakistan. The palynological sample derives from claystone stratigraphically positioned above the wood fossils, but pollen and spores as well as the wood are all of Oligocene age. The three fossil wood samples derive from the top of the lower unit of the Chitarwata Formation, and the palynological sample comes from claystone situated in the middle unit of the formation. The wood samples are described and found to represent two species of the morphotaxon Terminalioxylon (Combretaceae): T. burmense Mädel-Angeliewa and Müller-Stoll [Madel-Angeliewa, E., Müller-Stoll, W.R., 1973. Kritische Studien über fossile Combretaceen-Hölzer: über Hölzer von Typus Terminalioxylon G. Schönfeld mit einer Revision der bisher zu Evodioxylon Chiarugi gestellten Arten. Palaeontographica 142B, 117–136.] and T. sulaimanense sp. nov. These fossils are close to modern species of Terminalia, which occur in moist deciduous or semi-evergreen tropical forests. The palynological assemblage is composed of a mixture of pollen and spore types from different origins. There is a dominance of hygrophilous ferns, pines, Amaranthaceae–Chenopodiaceae–Caryophylaceae, but also the occurrence of Palmae, which are typical of tropical rainforests. This assemblage suggests that the depositional system is set in a context of nearby mountains with a minimum altitude of 2000 to 2500 m and characterized by differentiated forest belts above the tropical lowland vegetation of lower elevations. Wood, pollen and spores support the view of a fluvial environment surrounded by a tropical forested habitat. The separate stratigraphic position of the pollen assemblage above the fossil wood could explain its slightly different, more varied, palaeoenvironmental signal. 相似文献
999.
Chemical and Biological Interactions during Nitrate and Goethite Reduction by Shewanella putrefaciens 200
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D. Craig Cooper Flynn W. Picardal Arndt Schimmelmann Aaron J. Coby 《Applied microbiology》2003,69(6):3517-3525
Although previous research has demonstrated that NO3− inhibits microbial Fe(III) reduction in laboratory cultures and natural sediments, the mechanisms of this inhibition have not been fully studied in an environmentally relevant medium that utilizes solid-phase, iron oxide minerals as a Fe(III) source. To study the dynamics of Fe and NO3− biogeochemistry when ferric (hydr)oxides are used as the Fe(III) source, Shewanella putrefaciens 200 was incubated under anoxic conditions in a low-ionic-strength, artificial groundwater medium with various amounts of NO3− and synthetic, high-surface-area goethite. Results showed that the presence of NO3− inhibited microbial goethite reduction more severely than it inhibited microbial reduction of the aqueous or microcrystalline sources of Fe(III) used in other studies. More interestingly, the presence of goethite also resulted in a twofold decrease in the rate of NO3− reduction, a 10-fold decrease in the rate of NO2− reduction, and a 20-fold increase in the amounts of N2O produced. Nitrogen stable isotope experiments that utilized δ15N values of N2O to distinguish between chemical and biological reduction of NO2− revealed that the N2O produced during NO2− or NO3− reduction in the presence of goethite was primarily of abiotic origin. These results indicate that concomitant microbial Fe(III) and NO3− reduction produces NO2− and Fe(II), which then abiotically react to reduce NO2− to N2O with the subsequent oxidation of Fe(II) to Fe(III). 相似文献
1000.
Microbial Growth on Dichlorobiphenyls Chlorinated on Both Rings as a Sole Carbon and Energy Source 总被引:5,自引:0,他引:5
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We have isolated bacterial strains capable of aerobic growth on ortho-substituted dichlorobiphenyls as sole carbon and energy sources. During growth on 2,2′-dichlorobiphenyl and 2,4′-dichlorobiphenyl strain SK-4 produced stoichiometric amounts of 2-chlorobenzoate and 4-chlorobenzoate, respectively. Chlorobenzoates were not produced when strain SK-3 was grown on 2,4′-dichlorobiphenyl. 相似文献