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31.
If an adequate biocatalyst is identified for a specific reaction, immobilization is one possibility to further improve its
properties. The immobilization allows easy recycling, improves the enzyme performance, and it often enhances the stability
of the enzyme. In this work, the immobilization of the benzoylformate decarboxylase (BFD) variant, BFD A460I-F464I, from Pseudomonas putida was accomplished on spherical silica. Silicagel is characterized by its high mechanical stability, which allows its application
in different reactor types without restrictions. The covalently bound enzyme was characterized in terms of its activity, stability,
and kinetics for the formation of chiral 2-hydroxypropiophenone (2-HPP) from benzaldehyde and acetaldehyde. Moreover, temperature
as well as pressure dependency of immobilized BFD A460I-F464I activity and enantioselectivity were analyzed. The used wide-pore
silicagel shows a good accessibility of the immobilized enzyme. The activity of the immobilized BFD A460I-F464I variant was
determined to be 70% related to the activity of the free enzyme. Thereby, the enantioselectivity of the enzyme was not influenced
by the immobilization. In addition, a pressure-induced change in stereoselectivity was found both for the free and for the
immobilized enzyme. With increasing pressure, the enantiomeric excess (ee) of (R)-2-HPP can be increased from 44% (0.1 MPa) to 76% (200 MPa) for the free enzyme and from 43% (0.1 MPa) to 66% (200 MPa) for
the immobilized enzyme. 相似文献
32.
The immunomodulatory effects of three compounds designated BS, GS, and YS produced by Pestalotiopsis leucothës, an endophytic fungus isolated from Tripterygium wilfordii, were evaluated. The 50% inhibition concentration (IC50) value of BS in the proliferative assay with various stimulating agents such as phytohemagglutinin-M (PHA-M), phorbol myristate acetate (PMA)/ionomycin, mixed lymphocyte reaction (MLR) and poke weed mitogen (PWM) was 0.35, 1.6, 0.8 and 5.4 μg/ml, respectively. In addition, BS significantly inhibited the production of cytokines such as interleukin (IL)-1β, IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α, by peripheral blood mononuclear cells (PBMNC) and soluble IL-2 receptor expression at concentrations greater than 1 μg/ml. Inhibition of PHA stimulated PBMNC proliferation and IL-2 and sIL-2R production by BS indicates that it is a T-cell specific immunosuppressant. However, BS also moderately inhibited immunoglobulin (Ig) G and M at concentrations greater than 1 μg/ml suggesting that it also has B cell immunosuppressive effects. YS was 10% less active than BS in all assay systems. In contrast, GS exhibited both suppression and enhancement of PBMNC proliferation in the presence of various stimulants. However, GS inhibited PWM stimulated PBMNC proliferation and IL-4 and IgG and IgM production at concentrations above 1 μg/ml. All three fungal compounds altered the percentage of T-lymphocyte subpopulations only at high concentrations. Cell viability was not affected at the immunosuppressive concentrations of these compounds. In conclusion, work from our laboratory has identified three potentially potent immunomodulatory compounds from P. leucothës. These compounds have variable effects on T- and B-cells and monocytes. They may partially explain the immunosuppressive activity of T. wilfordii. In addition, they may represent a new source of immunomodulatory compounds for the treatment of human immune mediated diseases. 相似文献
33.
Ghrelin system in pancreatic AR42J cells: its ligand stimulation evokes calcium signalling through ghrelin receptors 总被引:5,自引:0,他引:5
Lai JK Cheng CH Ko WH Leung PS 《The international journal of biochemistry & cell biology》2005,37(4):887-900
Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The presence of ghrelin in pancreatic islet cells has been previously reported and it is known to increase the [Ca2+]i in (-cells, affecting insulin secretion. However, evidence for the existence of the ghrelin system and its calcium signalling pathway in the exocrine pancreas remains unclear. Thus this study aims, first, to investigate the expression of ghrelin and its receptor in pancreatic AR42J cells and, secondly, to elucidate its calcium signalling pathway. Our results showed that ghrelin and ghrelin receptor were consistently expressed in AR42J cells. Moreover, fluorescence imaging showed that cholecystokinin-8, ghrelin and growth hormone-releasing hexapeptide stimulate [Ca2+]i in AR42J cells in a dose-dependent manner. Ghrelin and the hexapeptide produced a biphasic elevation in [Ca2+]i with an initial transient increase, followed by a sustained plateau. In the presence of (D-Lys3)-GHRP-6, the [Ca2+]i evoked by ghrelin was suppressed. In the absence of extracellular Ca2+, the transient phase of the ghrelin response was maintained but greatly diminished while the plateau phase was completely abolished. Pretreatment with 2-aminoethoxydiphenyl borate and xestospongin C abolished the transient phase and inhibited the sustained phase of the ghrelin response. The stimulatory effect of ghrelin was also blocked by nifedipine. These results indicate that ligand stimulation of the ghrelin receptor could lead to a biphasic [Ca2+]i mobilization in these cells. These data suggests the presence of a ghrelin system in pancreatic AR42J cells. In addition, its roles in exocrine function are implicated in the pancreas. 相似文献
34.
ROCR: visualizing classifier performance in R 总被引:2,自引:0,他引:2
SUMMARY: ROCR is a package for evaluating and visualizing the performance of scoring classifiers in the statistical language R. It features over 25 performance measures that can be freely combined to create two-dimensional performance curves. Standard methods for investigating trade-offs between specific performance measures are available within a uniform framework, including receiver operating characteristic (ROC) graphs, precision/recall plots, lift charts and cost curves. ROCR integrates tightly with R's powerful graphics capabilities, thus allowing for highly adjustable plots. Being equipped with only three commands and reasonable default values for optional parameters, ROCR combines flexibility with ease of usage. AVAILABILITY: http://rocr.bioinf.mpi-sb.mpg.de. ROCR can be used under the terms of the GNU General Public License. Running within R, it is platform-independent. CONTACT: tobias.sing@mpi-sb.mpg.de. 相似文献
35.
Black WC Bayly CI Davis DE Desmarais S Falgueyret JP Léger S Li CS Massé F McKay DJ Palmer JT Percival MD Robichaud J Tsou N Zamboni R 《Bioorganic & medicinal chemistry letters》2005,15(21):4741-4744
The P2-P3 amide of dipeptide cathepsin K inhibitors can be replaced by the metabolically stable trifluoroethylamine group. The non-basic nature of the nitrogen allows the important hydrogen bond to Gly66 to be made. The resulting compounds are 10- to 20-fold more potent than the corresponding amide derivatives. Compound 8 is a 5 pM inhibitor of human cathepsin K with >10,000-fold selectivity over other cathepsins. 相似文献
36.
We use evolutionary trees of haplotypes to study phenotypic associations by exhaustively examining all possible biallelic partitions of the tree, a technique we call tree scanning. If the first scan detects significant associations, additional rounds of tree scanning are used to partition the tree into three or more allelic classes. Two worked examples are presented. The first is a reanalysis of associations between haplotypes at the Alcohol Dehydrogenase locus in Drosophila melanogaster that was previously analyzed using a nested clade analysis, a more complicated technique for using haplotype trees to detect phenotypic associations. Tree scanning and the nested clade analysis yield the same inferences when permutation testing is used with both approaches. The second example is an analysis of associations between variation in various lipid traits and genetic variation at the Apolipoprotein E (APOE) gene in three human populations. Tree scanning successfully identified phenotypic associations expected from previous analyses. Tree scanning for the most part detected more associations and provided a better biological interpretative framework than single SNP analyses. We also show how prior information can be incorporated into the tree scan by starting with the traditional three electrophoretic alleles at APOE. Tree scanning detected genetically determined phenotypic heterogeneity within all three electrophoretic allelic classes. Overall, tree scanning is a simple, powerful, and flexible method for using haplotype trees to detect phenotype/genotype associations at candidate loci. 相似文献
37.
38.
Highly active antiretroviral therapy (HAART), in which three or more drugs are given in combination, has substantially improved the clinical management of HIV-1 infection. Still, the emergence of drug-resistant variants eventually leads to therapy failure in most patients. In such a scenario, the high diversity of resistance-associated mutational patterns complicates the choice of an optimal follow-up regimen. To support physicians in this task, a range of bioinformatics tools for predicting drug resistance or response to combination therapy from the viral genotype have been developed. With several free and commercial software services available, computational advice is rapidly gaining acceptance as an important element of rational decision-making in the treatment of HIV infection. 相似文献
39.
Ciske FL Barbachyn MR Genin MJ Grega KC Lee CS Dolak LA Seest EP Watt W Adams WJ Friis JM Ford CW Zurenko GE 《Bioorganic & medicinal chemistry letters》2003,13(23):4235-4239
The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 microg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of alpha-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed. 相似文献
40.