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Identification of a new membrane-permeable inhibitor against inositol-1,4,5-trisphosphate-3-kinase A
Dominik Schröder Christoph Rehbach Carola Seyffarth Martin Neuenschwander Jens V. Kries Sabine Windhorst 《Biochemical and biophysical research communications》2013
Ectopic expression of the neuron-specific inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) in lung cancer cells increases their metastatic potential because the protein exhibits two actin regulating activities; it bundles actin filaments and regulates inositol-1,4,5-trisphosphate (InsP3)-mediated calcium signals by phosphorylating InsP3. Thus, in order to inhibit the metastasis-promoting activity of ITPKA, both its actin bundling and its InsP3kinase activity has to be blocked. In this study, we performed a high throughput screen in order to identify specific and membrane-permeable substances against the InsP3kinase activity. Among 341,44 small molecules, 237 compounds (0.7%) were identified as potential InsP3kinase inhibitors. After determination of IC50-values, the three compounds with highest specificity and highest hydrophobicity (EPPC-3, BAMB-4, MEPTT-3) were further characterized. Only BAMB-4 was nearly completely taken up by H1299 cells and remained stable after cellular uptake, thus exhibiting a robust stability and a high membrane permeability. Determination of the inhibitor type revealed that BAMB-4 belongs to the group of mixed type inhibitors. Taken together, for the first time we identified a highly membrane-permeable inhibitor against the InsP3kinase activity of ITPKA providing the possibility to partly inhibit the metastasis-promoting effect of ITPKA in lung tumor cells. 相似文献
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Philip Magnus Bahman Ghavimi Jotham W. Coe 《Bioorganic & medicinal chemistry letters》2013,23(17):4870-4874
(?)-Codeine 1 was converted into previously unknown 7β-methyl-7,8-dihydrocodeine/morphine derivatives such as 13 via classical diaxial opening of α-epoxide 3. Several analogs exhibited dual μ/δ-agonist activity. 相似文献
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Treatment of textile wastewater is a big challenge because of diverse chemical composition, high chemical strength and color of the wastewater. In the present study, treatment of wastewater containing reactive black-5 azo dye was studied in anaerobic sequencing batch bioreactor (SBBR) using mixed liquor suspended solids (MLSS) from suspended and attach growth bioreactors. MLSS at concentration of 1000 mg/L and reactive black-5 azo dye at 100 mg/L were used. A culture (108–109 CFU/ml) of pre-isolated bacterial strains (Psychrobacter alimentarius KS23 and Staphylococcus equorum KS26)) capable of degrading azo dyes in mineral salt medium was used to accelerate the treatment process in bioreactor. Different combinations of sludge, culture and dye were used for treatment using different co-substrates. About 85% COD removal was achieved by consortium (MLSS + KS23 + KS26) after 24 h in attach growth bioreactor. Similarly, 92% color removal was observed with consortium in attach growth bioreactor compared to 85% color removal in suspended bioreactor. Addition of bacterial culture (20%, v/v) to the bioreactor could enhance the rate of color removal. This study suggests that biotreatment of wastewater containing textile dyes can be achieved more efficiently in the attach growth bioreactor using yeast extract as a co-substrate and MLSS augmented with dye-degrading bacterial strains. 相似文献
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Chiara Fabris Wladimiro De Colle Giovanni Sparacino 《Biomedical signal processing and control》2013,8(6):920-926
The quantitative analysis of vocal disorders by nonlinear signal processing methods has been extensively used in the last two decades. In this work, two algorithms for nonlinear time-series analysis, Sample Entropy and cross-Sample Entropy, are used on electroglottogram (EGG) and microphone (MIC) signals recorded from 51 normal and 80 dysphonic subjects, to obtain summary measures of voice disorders through SampEn and cross-SampEn indices. Such parameters quantify, respectively, the degree of irregularity (in the sense of self-dissimilarity) within a time-series and of asynchrony (in the sense of cross-dissimilarity) between two distinct time-series. The aims of this work are: to determine if statistically significant differences in terms of signal irregularity quantified by SampEn occur between normal and pathological subjects, investigating whether or not such differences can be equally seen in EGG and MIC; to assess if cross-SampEn reveals different degrees of asynchrony between EGG and MIC signals in the two groups. Results show that SampEn in pathological subjects is higher than in normal subjects for both EGG and MIC time-series, with a statistically significant difference detectable from both signals (Pe < 10?4 for EGG and Pe < 10?7 for MIC). Cross-SampEn exhibits a statistically significant difference too, showing a higher degree of cross-dissimilarity between EGG and MIC time-series for pathological subjects (Pe < 10?4). In conclusion, SampEn and cross-SampEn well quantify the increase of complexity of both EGG and MIC signals and the decrease of their cross-similarity in presence of vocal disorders. Thanks to the complementarity of nonlinear indicators to the traditionally considered linear ones, SampEn and cross-SampEn appear as suitable candidates to enter the pool of approaches to investigate speech pathologies and to obtain potentially new insights on their nature. 相似文献
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Isothermal titration calorimetry data for very low c (≡K[M]0) must normally be analyzed with the stoichiometry parameter n fixed — at its known value or at any reasonable value if the system is not well characterized. In the latter case, ΔH° (and hence n) can be estimated from the T-dependence of the binding constant K, using the van't Hoff (vH) relation. An alternative is global or simultaneous fitting of data at multiple temperatures. In this Note, global analysis of low-c data at two temperatures is shown to estimate ΔH° and n with double the precision of the vH method. 相似文献
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We shall construct a class of nonlinear reaction-diffusion equations starting from an infinitesimal algebraic skeleton. Our aim is to explore the possibility of an algebraic foundation of integrability properties and of stability of equilibrium states associated with nonlinear models describing patterns formation. 相似文献