Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acanthamoeba castellanii transcription initiation factor-IB (TIF-IB) is the TATA-binding protein-containing transcription factor that binds the rRNA promoter to form the committed complex. Minor groove-specific drugs inhibit TIF-IB binding, with higher concentrations needed to disrupt preformed complexes because of drug exclusion by bound TIF-IB. TIF-IB/DNA interactions were mapped by hydroxyl radical and uranyl nitrate footprinting. TIF-IB contacts four minor grooves in its binding site. TIF-IB and DNA wrap around each other in a right-handed superhelix of high pitch, so the upstream and downstream contacts are on opposite faces of the helix. Dimethyl sulfate protection assays revealed limited contact with a few guanines in the major groove. This detailed analysis suggests significant DNA conformation dependence of the interaction.
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PMID:The fundamental ribosomal RNA transcription initiation factor-IB (TIF-IB, SL1, factor D) binds to the rRNA core promoter primarily by minor groove contacts. 936 Oct 4

An ammonium transporter cDNA, named TbAMT1, was isolated from the ectomycorrhizal ascomycetous truffle Tuber borchii. The polypeptide encoded by TbAMT1 (52 kDa) functionally complements ammonium uptake-defective yeast mutants and shares sequence similarity with previously characterized ammonium transporters from Saccharomyces (Mep) and Arabidopsis (AtAMT1). Structural characteristics common to the Mep/Amt family and peculiar features of the Tuber transporter have been evidenced by a detailed topological model of the TbAMT1 protein, which predicts 11 transmembrane helices with an N terminus(OUT)/C terminus(IN) orientation. As revealed by uptake/competition experiments conducted in yeast, TbAMT1 is a high-affinity transporter with an apparent K(m) for ammonium of 2 microM. The TbAMT1 mRNA was very slowly, yet specifically upregulated in nitrogen-deprived T. borchii mycelia. Instead, a much faster return to basal expression levels was observed upon resupplementation of either ammonium or nitrate, which thus appear to be utilized as equally effective nitrogen sources by Tuber mycelia.
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PMID:A high-affinity ammonium transporter from the mycorrhizal ascomycete Tuber borchii. 1205 92

External hyphae, which play a key role in nitrogen nutrition of trees, are considered as the absorbing structures of the ectomycorrhizal symbiosis. Here, we have cloned and characterized Hebeloma cylindrosporum AMT1, GLNA and GDHA genes, which encode a third ammonium transporter, a glutamine synthetase and an NADP-dependent glutamate dehydrogenase respectively. Amt1 can fully restore the pseudohyphal growth defect of a Saccharomyces cerevisiae mep2 mutant, and this is the first evidence that a heterologous member of the Mep/Amt family complements this dimorphic change defect. Dixon plots of the inhibition of methylamine uptake by ammonium indicate that Amt1 has a much higher affinity than the two previously characterized members (Amt2 and Amt3) of the Amt/Mep family in H. cylindrosporum. We also identified the intracellular nitrogen pool(s) responsible for the modulation of expression of AMT1, AMT2, AMT3, GDHA and GLNA. In response to exogenously supplied ammonium or glutamine, AMT1, AMT2 and GDHA were downregulated and, therefore, these genes are subjected to nitrogen repression in H. cylindrosporum. Exogenously supplied nitrate failed to induce a downregulation of the five mRNAs after transfer of mycelia from a N-starved condition. Our results demonstrate that glutamine is the main effector for AMT1 and AMT2 repression, whereas GDHA repression is controlled by intracellular ammonium, independently of the intracellular glutamine or glutamate concentration. Ammonium transport activity may be controlled by intracellular NH4+. AMT3 and GLNA are highly expressed but not highly regulated. A model for ammonium assimilation in H. cylindrosporum is presented.
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PMID:Molecular characterization, function and regulation of ammonium transporters (Amt) and ammonium-metabolizing enzymes (GS, NADP-GDH) in the ectomycorrhizal fungus Hebeloma cylindrosporum. 1251 92

A group of 3'-O-nitro-2'-deoxyuridines, 3'-O-nitro-2'-deoxycytidines, and 5'-O-nitro-2'-deoxyuridines possessing a variety of substituents (H, Me, F, I) at the C-5 position were synthesized for evaluation as anticancer/antiviral agents that have the ability to concomitantly release cytotoxic nitric oxide (*NO). Although these compounds generally released a greater percent of *NO than the reference drug isosorbide dinitrate upon incubation in the presence of l-cysteine, or serum, their cytotoxicity (CC(50) = 10(-3) to 10(-6) M range) was comparable to 5-iodo-2'-deoxyuridine, but weaker than 5-fluoro-2'-deoxyuridine, against a variety of cancer cell lines. No differences in cytotoxicity against nontransfected (KBALB, 143B), and the corresponding transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK(+)) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect. These nitrate esters were inactive antiviral agents except for 5-iodo-3'-O-nitro-2'-deoxyuridine that showed modest activity against HSV-1, HSV-2, and vaccinia virus.
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PMID:Synthesis of 3'- and 5'-nitrooxy pyrimidine nucleoside nitrate esters: "nitric oxide donor" agents for evaluation as anticancer and antiviral agents. 1262 76

The effect of calcium salt content in the poly(epsilon-caprolactone) (PCL)/silica nanocomposite on the nucleation and growth behavior of apatite layer in simulated body fluid (SBF) was investigated. The specimens were prepared with low (L) and high (H) concentrations of calcium nitrate tetrahydrate through a sol-gel method. After soaking in the SBF at 36.5 degrees C for 1 week, a densely packed apatite layer that had a smooth surface and a Ca/P ratio similar to bone was formed on specimens containing a low concentration of calcium salt while a loosely packed apatite layer with a rugged surface and a higher Ca/P ratio than that of bone occurred on specimens containing a high concentration of calcium salt. The results are explained in terms of the degree of supersaturation of apatite in the SBF, as determined by the concentrations of constituent ions of apatite and pH. The practical implication of the results is that a dense and bone-like apatite layer on the PCL/silica nanocomposite in vitro, and perhaps in vivo, can be achieved by adopting an appropriate calcium salt content.
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PMID:Effect of calcium salt content in the poly(epsilon-caprolactone)/silica nanocomposite on the nucleation and growth behavior of apatite layer. 1462 98

A novel poly(epsilon-caprolactone)-organosiloxane hybrid material containing calcium salt (Si-O-PCL) was prepared and evaluated as a bioactive and degradable bone substitute material. The Si-O-PCL hybrid was synthesized by the end-capping of 3-isocyanatopropyl triethoxysilane with alpha,omega-hydroxyl PCL following sol-gel reaction with calcium nitrate tetrahydrate. Its tensile mechanical properties were evaluated, and additional specimens were exposed to simulated body fluid (SBF) for the time range from 3 h to 7 days. The SBF exposure led to the deposition of a layer of apatite crystals on the surface of the Si-O-PCL hybrid within 9 h of soaking. The tensile strength was around 18 MPa, Young's modulus was around 200 MPa, and the strain at break was around 290%. This material is likely to have a potential application as a bioactive and degradable bone substitute because of its apatite forming ability, biodegradability, and mechanical properties comparable to those of human cancellous bone.
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PMID:Evaluation of a novel poly(epsilon-caprolactone)-organosiloxane hybrid material for the potential application as a bioactive and degradable bone substitute. 1524 80

A novel anaerobic, moderately thermophilic, spore-forming bacterium, designated strain BRT, was isolated from deep-sea hydrothermal core samples collected at the Rainbow vent field on the Mid-Atlantic Ridge (36 degrees 14' N 33 degrees 54' W). The cells were found to be rod-shaped, non-motile, Gram-positive and spore-forming. The organism grew in the temperature range 37-60 degrees C, with an optimum at 55 degrees C, and at pH values in the range 6-8.5, with an optimum around pH 7. NaCl concentrations for growth were in the range 10-40 g l(-1), with an optimum at 20-30 g l(-1). Strain BRT grew chemo-organoheterotrophically with carbohydrates, proteinaceous substrates and organic acids with nitrate as electron acceptor. The novel isolate was not able to ferment. The G+C content of the genomic DNA was 34.5 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed strain BRT in the Bacillaceae within the class 'Bacilli'. On the basis of the phenotypic and phylogenetic data, this isolate should be described as a member of a novel genus, for which the name Vulcanibacillus gen. nov. is proposed. The type species is Vulcanibacillus modesticaldus sp. nov., with the type strain BRT (=DSM 14931T=JCM 12998T).
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PMID:Vulcanibacillus modesticaldus gen. nov., sp. nov., a strictly anaerobic, nitrate-reducing bacterium from deep-sea hydrothermal vents. 1662 53

It is well known that exposure to cis-diaminedichloroplatinum (CDDP) results in impairment of spermatogenesis; however, little is known about the signal mechanisms involved in CDDP regulation of Sertoli cell (SC) function. This study was designed to evaluate how CDDP regulates SC signal molecules and mechanisms. Purified rat SC was cultured under serum-free conditions and treated with CDDP (10 ng/ml) at various time points. Western blot analysis was used to determine the activation of extracellular signal-related kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), cJun-N-terminal kinase (JNK), cyclooxygenase (COX)-1 and COX-2, inducible and endothelial nitric oxide synthase (iNOS and eNOS). The levels of transferrin (TF) and prostaglandin (PG)E2, PGF2alpha, PGD2, carbaprostacyclin (cPGI2 analog) in culture medium were quantified by ELISA. Nitrite (NO2(-)) and nitrate (NO3(-)) in culture medium were also quantified by Griess assay. Interleukin (IL)-1beta and IL-6 mRNAs were measured by quantitative real-time PCR (QRT-PCR) analysis. CDDP activated the phosphorylation of ERK1/2 (p-ERK1/2) in the early phase (within 5 min) and the level of transferrin (TF) fell significantly. In addition, CDDP significantly increased the level of COX-2, PGs, and ILs in the late phase (within 24h). When ERK activity inhibitor (PD98059, 10 microM) or COX-2 activity inhibitor (NS-398, 10 microM) was used, CDDP reduction of TF and induction of PG and IL expression were prevented, suggesting that the detrimental effects on spermatogenesis through the impairment of SC induced by CDDP are mediated by the activation of ERK1/2 and COX-2 pathways in SC.
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PMID:Cisplatin regulates Sertoli cell expression of transferrin and interleukins. 1824 79

Increased nitric oxide (NO) has been correlated with diabetic retinopathy. In this study we investigated the cell injury, production of NO in retinal pigment epithelial (RPE) cells exposed to increased glucose concentration, and its molecular mechanism involved. Cultured human RPE cells (ARPE-19) were exposed for 4 days with normal blood glucose concentration (5.5mM D-glucose), followed by exposure to either normal (5.5mM) or high (33 mM) concentrations of D-glucose for 48 h. To determine the cytotoxicity of high glucose, cell viability, ROS production and SOD activity were measured, respectively. The end product of NO (nitrite and nitrate) was determined by a colorimetric assay and nitrotyrosine levels were quantified by a competitive ELISA. The expression of iNOS and the activation of p38MAPK, ERK and JNK were analyzed by Western blot. Treatment of RPE cells with high glucose-induced a significant increased of iNOS, accompanied by an increase in cell damage, NO and nitrotyrosine levels. High glucose caused activation of p38MAPK and ERK, inhibition for p38MAPK and ERK abrogated the high glucose-induced increase in iNOS, cell injury and levels of NO and nitrotyrosine. High glucose causes increased cell damage and NO generation in RPE cells by a process of iNOS expression that requires the activation of p38MAPK and ERK.
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PMID:p38MAPK and ERK promote nitric oxide production in cultured human retinal pigmented epithelial cells induced by high concentration glucose. 1885 22

The application of diffuse pollution models included in EUROHARP encompassed varying levels of parameterisation and approaches to the preparation of input data depending on the model and modelling team involved. Modellers consistently faced important decisions in relation to data interpretation, especially in those catchments with unfamiliar physical or climatic characteristics, where catchment conditions were beyond the range for which a particular model was originally developed, or where only limited input data were available. In addition to a broad discussion of data issues, this paper compares the performance of the four sub-annual output models tested in EUROHARP (EveNFlow, NL-CAT, SWAT and TRK) in three test catchments without the modelling teams having sight of measured flow and nitrate concentration data. Model performance in this "blind test" indicate that the range of predictions generated by any individual models pre and post calibration exceed the differences between the estimates yielded by all four models. Comparison of Analysis of Variance (ANOVA) statistics for simulated and observed flow, concentration and loads underscores the benefits of calibration for these intermediate and complex model formulations. Interpretation of input data (e.g. rainfall interpolation method and pedotransfer functions selected) appeared equally (or more) important than process representation. In the absence of calibration data, modeller unfamiliarity with a particular catchment and its environmental processes sometimes resulted in questionable assumptions and input errors which highlight the problems facing modellers charged with implementing policies under the Water Framework Directive (2000/60/EC) in poorly monitored catchments. Catchment data owners and modellers must therefore work more closely given that the output from diffuse pollution models is clearly modeller-limited as well as model-limited.
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PMID:Evaluation of diffuse pollution model applications in EUROHARP catchments with limited data. 1928 34


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