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131.
Dhar P Meng TC Somani S Ye L Sairam A Chitre M Hao Z Sakharkar K 《Bioinformatics (Oxford, England)》2004,20(8):1319-1321
The intracellular environment of a cell hosts a wide variety of enzymatic reactions, diffusion events, molecular binding, polymerization and metabolic channeling. To transform these biological events into a computational framework, distinct modeling strategies are required. While currently no tool is capable of capturing all these events, progress is being made to create an integrated environment for the modeling community. To address this niche requirement, Cellware has been developed to offer a multi-algorithmic environment for modeling and simulating both deterministic and stochastic events in the cell. AVAILABILITY: The software is available for free and can be downloaded from http://www.bii.a-star.edu.sg/sbg/cellware 相似文献
132.
Verma S Srivatsan SG Claussen CA Long EC 《Bioorganic & medicinal chemistry letters》2003,13(15):2501-2504
Cleavage of a model phosphate ester and supercoiled plasmid DNA by a Cu(I).adenylated polymer template and preliminary mechanistic investigations are reported. A novel paradigm for the design of recyclable nucleolytic reagents allowing multiple use of this catalyst is also demonstrated 相似文献
133.
Yadav R Yoshimura Y Boesteanu A Christianson GJ Ajayi WU Shashidharamurthy R Stanic AK Roopenian DC Joyce S 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(10):5133-5142
Minor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign. We used a combinational peptide screening approach to identify the immune dominant H2K(b)-restricted epitope defining the mouse H4(b) minor H Ag. H4(b) is a consequence of a P3 threonine to isoleucine change in the MHC-bound peptide derived from epithelial membrane protein-3. This allelic variation also leads to phosphorylation of the H4(b) but not the H4(a) epitope. Further, ex vivo CD8(+) T lymphocytes bind phosphorylated Ag tetramers with high efficiency. Although we document the above process in the minor H Ag system, posttranslational modifications made possible by subtle amino acid changes could also contribute to immunogenicity and immune dominance in tumor immunotherapeutic settings. 相似文献
134.
Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases 总被引:9,自引:0,他引:9
Modular polyketide synthases (PKSs) are large multi-enzymatic, multi-domain megasynthases, which are involved in the biosynthesis of a class of pharmaceutically important natural products, namely polyketides. These enzymes harbor a set of repetitive active sites termed modules and the domains present in each module dictate the chemical moiety that would add to a growing polyketide chain. This modular logic of biosynthesis has been exploited with reasonable success to produce several novel compounds by genetic manipulation. However, for harnessing their vast potential of combinatorial biosynthesis, it is essential to develop knowledge based in silico approaches for correlating the sequence and domain organization of PKSs to their polyketide products. In this work, we have carried out extensive sequence analysis of experimentally characterized PKS clusters to develop an automated computational protocol for unambiguous identification of various PKS domains in a polypeptide sequence. A structure based approach has been used to identify the putative active site residues of acyltransferase (AT) domains, which control the specificities for various starter and extender units during polyketide biosynthesis. On the basis of the analysis of the active site residues and molecular modelling of substrates in the active site of representative AT domains, we have identified a crucial residue that is likely to play a major role in discriminating between malonate and methylmalonate during selection of extender groups by this domain. Structural modelling has also explained the experimentally observed chiral preference of AT domain in substrate selection. This computational protocol has been used to predict the domain organization and substrate specificity for PKS clusters from various microbial genomes. The results of our analysis as well as the computational tools for prediction of domain organization and substrate specificity have been organized in the form of a searchable computerized database (PKSDB). PKSDB would serve as a valuable tool for identification of polyketide products biosynthesized by uncharacterized PKS clusters. This database can also provide guidelines for rational design of experiments to engineer novel polyketides. 相似文献
135.
The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells 总被引:7,自引:0,他引:7
Krishnan S Warke VG Nambiar MP Tsokos GC Farber DL 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(8):4189-4195
The TCR-mediated signals required to activate resting T cells have been well characterized; however, it is not known how TCR-coupled signals are transduced in differentiated effector T cells that coordinate ongoing immune responses. Here we demonstrate that human effector CD4 T cells up-regulate the expression of the CD3zeta-related FcRgamma signaling subunit that becomes part of an altered TCR/CD3 signaling complex containing CD3epsilon, but not CD3zeta. The TCR/CD3/FcRgamma complex in effector cells recruits and activates the Syk, but not the ZAP-70, tyrosine kinase. This physiologic switch in TCR signaling occurs exclusively in effector, and not naive or memory T cells, suggesting a potential target for manipulation of effector responses in autoimmune, malignant, and infectious diseases. 相似文献
136.
The difference between the heat (T(G)) and the cold (T(G)') denaturation temperatures defines the temperature range (T(Range)) over which the native state of a reversible two-state protein is thermodynamically stable. We have performed a correlation analysis for thermodynamic parameters in a selected data set of structurally nonhomologous single-domain reversible two-state proteins. We find that the temperature range is negatively correlated with the protein size and with the heat capacity change (DeltaC(p)) but is positively correlated with the maximal protein stability [DeltaG(T(S))]. The correlation between the temperature range and maximal protein stability becomes highly significant upon normalization of the maximal protein stability with protein size. The melting temperature (T(G)) also shows a negative correlation with protein size. Consistently, T(G) and T(G)' show opposite correlations with DeltaC(p), indicating a dependence of the T(Range) on the curvature of the protein stability curve. Substitution of proteins in our data set with their homologues and arbitrary addition or removal of a protein in the data set do not affect the outcome of our analysis. Simulations of the thermodynamic data further indicate that T(Range) is more sensitive to variations in curvature than to the slope of the protein stability curve. The hydrophobic effect in single domains is the principal reason for these observations. Our results imply that larger proteins may be stable over narrower temperature ranges and that smaller proteins may have higher melting temperatures, suggesting why protein structures often differentiate into multiple substructures with different hydrophobic cores. Our results have interesting implications for protein thermostability. 相似文献
137.
Somatic embryogenesis in callus cultures of Commiphora wightii (Arnott.) Bhandari was achieved. Though the frequency of explants producing embryonic culture was low, immature zygotic embryos were the only suitable explants to produce embryonic callus after reciprocal transfers on media containing 2,4,5-trichlorophenoxy acetic acid (0.1 mgl(-1)) and kinetin (0.1 mgl(-1)) or devoid of growth regulators. All other media failed to produce embryonic callus. Embryonic cells were small, densely filled with cytoplasm and isodiametric as compared to non-embryonic cells, which were large, elongated and vacuolated. Maximum growth of embryonic callus was recorded on modified MS medium (MS-2 medium) supplemented with BA (0.25 mgl(-1)) and IBA (0.1 mgl(-1)). MS-2 salts supported higher growth of callus as compared to tissues grown on B5 medium containing same concentrations of plant growth regulators. Exogenous medium nutrients had no effect on somatic embryo development whereas plant growth regulators had little effect. Asynchronously growing embryos formed plantlets regularly which were successfully transferred to the field conditions. 相似文献
138.
Aggarwal N.K. Niga P. Singh D. Yadav B.S. 《World journal of microbiology & biotechnology》2001,17(8):783-787
A commercial preparation of -amylase, Biotempase, obtained from Biocon India Pvt. Ltd., and crude glucoamylase produced from Aspergillus sp. NA21 were used to hydrolyse tapioca powder, a non-conventional starchy substrate. Among various concentrations of starch (15–35%, dry weight/volume) tried for maximum liquefaction; slurry made with 25% substrate concentration proved optimal. An economical process of liquefaction was carried out using steam under pressure (0.2–0.3 bar, 104–105 °C) to liquefy a 25% slurry in just 45 min, contrary to a slower process carried out at 95 °C in a water bath. For liquefaction of starch a pH of 5.0 proved to be optimum. The dose of Biotempase as prescribed by the supplier could be reduced by 33% achieving the same degree of liquefaction, by addition of CaCl2 to the starch slurry at the concentration of 120 mg/l. The conditions for the saccharification of liquefied starch were optimized to be 60 °C and pH 5.0, producing 90% saccharification in 24 h. Supplementation of divalent ions Ca2+, Mg2+ and Zn2+ in the process of saccharification showed no effect. Finally glucose was found to be the main hydrolysis product in the saccharification of tapioca starch. 相似文献
139.
140.
Lin S Chao PY Chien YW Sayani S Kuma S Mason M Wes T Yang A Monkhouse D 《AAPS PharmSciTech》2001,2(3):55-65
This investigation evaluated the feasibility of using subdermally implantable devices fabricated by nonconventional 3-dimensional
printing technology for controlled delivery of ethinyl estradiol (EE2). In vitro release kinetics of EE2 and in vivo pharmacokinetics pharmacodynamics in ovariectomized New Zealand White rabbits were carried out to study 3 implant
prototypes: implant I (single-channel EE2 distribution in polycaprolactone polymer core), implant II (homogeneous EE2 distribution in polycaprolactone polymer matrix), and implant III (concentration-gradient EE2 distribution in polycaprolactone and poly(dl-lactide-co-glycolide) (50∶50 matrix). EE2 was found to be released from all the implants in a nonlinear pattern with an order of implant III>implant II>implant I.
The noncompartmental pharmacokinetic analysis of plasma EE2 profiles in rabbits indicated a significant difference (p>.05) in Cmax, tmax, and mean residence time between implant I and implants II and III, but no difference in the area under the plasma concentration
time curves calculated by trapezoidal rule (AUC) among the implants. For pharmacodynamic studies, endogenous follicle-stimulating
hormone (FSH) and luteinizing hormone (LH) levels were observed to be suppressed following implantation of all implants, which
demonstrated that a therapeutically effective dose of EE2 had been delivered. Furthermore, the noncompartmental analysis of plasma FSH and LH profiles in rabbits showed a significant
difference (p<.05) in AUC and the mean residence time between implant III and implants I and II. A good in vivo/in vitro relationship was
observed between daily amounts of EE2 released and plasma profiles of EE2 for all implants. This relationship suggests that plasma profiles of EE2 could be predicted from in vitro measurement of daily amount of EE2 released Therefore, performing in vitro drug release studies may aid in the development of an EE2 implant with the desired in vivo release rate.
Published: September 21, 2001 相似文献