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991.
The genome structure of Pseudomonas putida: high-resolution mapping and microarray analysis 总被引:1,自引:0,他引:1
Stjepandić D Weinel C Hilbert H Koo HL Diehl F Nelson KE Tümmler B Hoheisel JD 《Environmental microbiology》2002,4(12):819-823
As part of a collaborative project aimed at sequencing and functionally analysing the entire genome of Pseudomonas putida strain KT2440, a physical clone map was produced as an initial resource. To this end, a high-coverage cosmid library was arrayed and ordered by clone hybridizations. Restriction fragments generated by rare-cutting enzymes and plasmids containing the rrn operon and 23S rDNA of Pseudomonas aeruginosa were used as probes and, parts of the cosmids were end-sequenced. This provided the information necessary for merging and comparing the macro-restriction map, cosmid clone order and sequence information, thereby assuring co-linearity of the eventual sequence assembly with the actual genome. A tiling path of clones was selected, from the shotgun clones used for sequencing, for the production of DNA microarrays that represent the entire genome including its non-coding portions. 相似文献
992.
Suh YG Lee YS Min KH Park OH Seung HS Kim HD Park HG Choi J Lee J Kang SW Oh UT Koo JY Joo YH Kim SY Kim JK Park YH 《Bioorganic & medicinal chemistry letters》2003,13(24):4389-4393
A novel non-vanilloid VR1 antagonist consisting of a new vanilloid equivalent exhibits excellent analgesic effects as well as highly potent antagonistic activities in both capsaicin single channel and calcium uptake assays. In addition, the structural requirement for the vanilloid equivalent of the potent VR1 antagonist has also been elucidated. 相似文献
993.
Lee JH Lee KS Kang YK Yoo KH Shin KJ Kim DC Kong JY Lee Y Lee SJ Kim DJ 《Bioorganic & medicinal chemistry letters》2003,13(24):4399-4403
The synthesis and antibacterial activity of novel 1β-methylcarbapenems 1a–f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem. 相似文献
994.
Kim KM Kim KH Kang TC Kim WY Lee Mr Jung HJ Hwang IK Ko SB Koh JY Won MH Oh Eg Shin I 《Bioorganic & medicinal chemistry letters》2003,13(14):2273-2275
In order to develop therapeutic agents against neurodegenerative diseases, we designed novel antioxidants containing N-t-butyl-N-hydroxylaminophenyl moieties and evaluated in vitro and in vivo neuroprotective properties as well as anti-ischemic effects. 相似文献
995.
Kang YK Lee KS Yoo KH Shin KJ Kim DC Lee CS Kong JY Kim DJ 《Bioorganic & medicinal chemistry letters》2003,13(3):463-466
The synthesis of novel 1 beta-methylcarbapenems 1a,b bearing isothiazoloethenyl moieties at C-5 position of pyrrolidine ring and their biological evaluation are described. Both compounds showed potent and well-balanced antibacterial activity as well as high stability to DHP-I. Especially, 5-isothiazole derivative 1a exhibited excellent DHP-I stability and advanced pharmacokinetics profiles, compared to 5-isoxazole derivative 2, imipenem, and meropenem. 相似文献
996.
997.
Previous work has shown that a low dietary intake of zinc for a short duration significantly lowers the lymphatic absorption
of α-tocopherol (αTP) in adult male rats. The present study investigated whether the nutritional status of zinc is critical
in maintaining the tissue levels of the vitamin. One group of rats was fed an AIN-93G diet containing 3 mg zinc/kg (low zinc,
LZ) and the other was fed the same diet but containing 30 mg zinc/kg (adequate zinc, AZ). Food intakes between groups were
matched by feeding two meals per day. At 6 wk, the body weights (356±8 g) of LZ rats reached 98% those (362±10 g) of AZ rats.
Feeding of the LZ diet for 6 wk significantly lowered the concentrations of both αTP and zinc in the liver, kidney, heart,
testis, and brain. No consistent relationships between αTP and zinc concentrations were observed in other tissues such as
spleen, lung, gastrocnemius muscle, and retroperitoneal fat tissues. The concentrations of αTP in the liver, testis, brain,
spleen, heart, and kidney were significantly correlated with the tissue concentrations of zinc. The LZ diet slightly but significantly
increased the total lipid contents (mg/g) of liver, kidney, heart, and spleen. However, the tissue levels of phospholipid
(μmol/100 mg lipid) in the heart, lung, testis, and spleen were decreased significantly in LZ rats. These findings indicate
that low zinc intake results in a pronounced decrease in the animal’s αTP status under the conditions of matched food intakes,
body weights, and feeding patterns. The lower tissue levels of αTP may explain in part the compromised antioxidant defense
system and increased susceptibility to oxidative damage observed in zinc deficiency. 相似文献
998.
999.
Kang SK Yi KS Kwon NS Park KH Kim UH Baek KJ Im MJ 《The Journal of biological chemistry》2004,279(35):36593-36600
A multifunctional enzyme, G(h), is a GTP-binding protein that couples to the alpha(1B)-adrenoreceptor and stimulates phospholipase C-delta1 but also displays transglutaminase 2 (TG2) activity. G(h)/TG2 has been implicated to play a role in cell motility. In this study we have examined which function of G(h)/TG2 is involved in this cellular response and the molecular basis. Treatment of human aortic smooth muscle cell with epinephrine inhibits migration to fibronectin and vitronectin, and the inhibition is blocked by the alpha(1)-adrenoreceptor antagonist prazosin or chloroethylclonidine. Up-regulation or overexpression of G(h)/TG2 in human aortic smooth muscle cells, DDT1-MF2, or human embryonic kidney cells, HEK 293 cells, results in inhibition of the migratory activity, and stimulation of the alpha(1B)-adrenoreceptor with the alpha(1) agonist further augments the inhibition of migration of human aortic smooth muscle cells and DDT1-MF2. G(h)/TG2 is coimmunoprecipitated by an integrin alpha(5) antibody and binds to the cytoplasmic tail peptide of integrins alpha(5), alpha(v), and alpha(IIb) subunits in the presence of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS). Mutation of Lys-Arg residues in the GFFKR motif, present in the alpha(5)-tail, significantly reduces the binding of GTPgammaS-G(h)/TG2. Moreover, the motif-containing integrin alpha(5)-tail peptides block G(h)/TG2 coimmunoprecipitation and reverse the inhibition of the migratory activity of HEK 293 cells caused by overexpression G(h)/TG2. These results provide evidence that G(h) function initiates the modulation of cell motility via association of GTP-bound G(h)/TG2 with the GFFKR motif located in integrin alpha subunits. 相似文献
1000.
DA-8159 is a pyrazolopyrimidinone derivative which is a potent and selective phosphodiesterase type 5 inhibitor. The efficacy of oral DA-8159 has been demonstrated in conscious and spinalized rabbits by its enhancement of nitric oxide-induced erections. The aim of this study was to investigate the time dependency of this efficacy on its plasma concentration in rabbits. DA-8159 was given orally to normal rabbits at a dose of 10 or 30 mg/kg in order to determine its pharmacokinetic parameters. After then, to investigate the relationship between penile erectile activity and plasma half-life, a dose of 10 mg/kg DA-8159 was administered and the erectile response was examined in a time-course manner by measuring the length of the uncovered penile mucosa after the intravenous administration of sodium nitroprusside, which was administered 1, 3, 6, 8, 24 hours after administering DA-8159. DA-8159 was absorbed rapidly with a Tmax of 0.6 hours in 30 mg/kg and 1.0 hour in the 10 mg/kg group, and T1/2 of 1.23 hours in 30 mg/kg and 1.17 hours in 10 mg/kg, respectively. DA-8159 was not detected in the blood plasma 3 hours (10 mg/kg) or 6 hours (30 mg/kg) after administration. In an erection test, DA-8159 alone (10 mg/kg) induced a penile erection for approximately 2 hours but there was no significant erection thereafter. Although the DA-8159-induced penile erection disappeared, an intravenous injection of sodium nitroprusside significantly induced a penile erection for 6 hours, when the plasma drug concentration was below the detection limit and a no longer visible erection was noted. These results demonstrate that DA-8159 is absorbed and rapidly cleared in rabbits. In addition, it can enhance a sodium nitroprusside-induced penile erection even after 6 hours, which is approximately five times longer than the plasma half-life in the rabbits. These results suggest that DA-8159 may have an erectile potential for much longer than its measured half-life. 相似文献