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2.
Star STING is the latest version of the STING suite of programs and corresponding database. We report on five important aspects of this package that have acquired some new characteristics, designed to add key advantages to the whole suite: 1) availability for most popular platforms and browsers, 2) introduction of the STING_DB quality assessment, 3) improvement in algorithms for calculation of three STING parameters, 4) introduction of five new STING modules, and 5) expansion of the existing modules. Star STING is freely accessible at: http://sms.cbi.cnptia.embrapa.br/SMS/, http://trantor.bioc.columbia.edu/SMS, http://www.es.embnet.org/SMS/, http://gibk26.bse.kyutech.ac.jp/SMS/ and http://www.ar.embnet.org/SMS. 相似文献
3.
MOTIVATION: Visualization is indispensable in the research of complex biochemical networks. Available graph layout algorithms are not adequate for satisfactorily drawing such networks. New methods are required to visualize automatically the topological architectures and facilitate the understanding of the functions of the networks. RESULTS: We propose a novel layout algorithm to draw complex biochemical networks. A network is modeled as a system of interacting nodes on squared grids. A discrete cost function between each node pair is designed based on the topological relation and the geometric positions of the two nodes. The layouts are produced by minimizing the total cost. We design a fast algorithm to minimize the discrete cost function, by which candidate layouts can be produced efficiently. A simulated annealing procedure is used to choose better candidates. Our algorithm demonstrates its ability to exhibit cluster structures clearly in relatively compact layout areas without any prior knowledge. We developed Windows software to implement the algorithm for CADLIVE. AVAILABILITY: All materials can be freely downloaded from http://kurata21.bio.kyutech.ac.jp/grid/grid_layout.htm; http://www.cadlive.jp/ SUPPLEMENTARY INFORMATION: http://kurata21.bio.kyutech.ac.jp/grid/grid_layout.htm; http://www.cadlive.jp/ 相似文献
4.
This data paper describes the native vascular aquatic plant floras of 268 Japanese lakes recorded from 1899–2011. The data were compiled from 201 literature sources, most of which were written in Japanese and published in local journals or individual reports rather than in major scientific journals. The literature was searched using web-based services (i.e., Google Scholar, http://scholar.google.com/; CiNii, http://ci.nii.ac.jp/en; JDreamII, http://pr.jst.go.jp/jdream2/; and ISI, http://apps.webofknowledge.com) and by private communication with experts or local governments. Scientific names were consolidated under currently-accepted nomenclature. Four datasets, FloraDB, LakeDB, SpeciesDB, and LiteratureDB, were created to include records of the flora of each lake in each year, the names and locations of the lakes, the scientific names and synonyms of the aquatic vascular plants, and a literature list, respectively. These data can be used to study long-term changes in the species composition and/or richness of aquatic plants in Japanese lakes. 相似文献
5.
Using Japanese literature, we created a consolidated list of host records of butterflies in Japan. The list used the host records described in eight major illustrated reference books, two checklists, and 14 other pieces of literature. The presence of larvae on plants, the observation of larvae eating plants or insects in the field were considered as host records. We collected all species recorded in Japan. Scientific, family, and Japanese names of butterflies were consolidated using the BINRAN database ( http://binran.lepimages.jp/). Scientific and Japanese names of host plants were based on the YList database ( http://ylist.info/). If scientific names of host plants were not found in YList, we used scientific names based on The Plant List ( http://www.theplantlist.org/). Family names of host plants were based on the Catalogue of Life database ( http://www.catalogueoflife.org/). Scientific, family, and Japanese names of host insects were based on the MOKUROKU database ( http://konchudb.agr.agr.kyushu-u.ac.jp/mokuroku/) for Hymenoptera and the catalogue of the Paraneoptera of Japan published by the Entomological Society of Japan for Hemiptera. We also provided the references of each host record and the original names described in the referred literature. Two datasets, HostDB and ReferenceDB, were created to include 3600 records of butterfly larval hosts in Japan, along with scientific and Japanese names of each species and a literature list. These datasets will be useful for basic and applied biological studies of butterflies. Data files are stored in the Ecological Research Data Archives ( http://db.cger.nies.go.jp/JaLTER/ER_DataPapers/) and available from http://hostbj.lepumus.net/. These datasets are published under the Creative Commons License Attribution-ShareAlike 4.0 (CC BY-SA, https://creativecommons.org/licenses/by-sa/4.0/). 相似文献
6.
We demonstrated recently that norepinephrine activates Ca 2+-permeable nonselective cation channels (NSCCs) in Chinese hamster ovary cells stably expressing 1A-adrenergic receptors (CHO- 1A). Moreover, extracellular Ca 2+ through NSCCs plays essential roles in norepinephrine-induced arachidonic acid release. The purpose of the present study was to identify the G proteins involved in the activation of NSCCs and arachidonic acid release by norepinephrine. For these purposes, we used U73122 , an inhibitor of phospholipase C (PLC), and dominant negative mutants of G12 and G13 (G12G228A and G13G225A, respectively). U73122 failed to inhibit NSCCs activation by norepinephrine. The magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO-1A microinjected with G13G225A were smaller than those in CHO-1A. In contrast, the magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO-1A microinjected with G12G228A were similar to those in CHO-1A. In addition, neither a Rho-associated kinase (ROCK) inhibitor nor a phosphoinositide 3-kinase inhibitor affected norepinephrine-induced extracellular Ca2+ influx. G13G225A, but not G12G228A, also inhibited arachidonic acid release partially. These results demonstrate that 1) the Gq/PLC-pathway is not involved in NSCCs activation by norepinephrine, 2) G13 couples with CHO-1A and plays important roles for norepinephrine-induced NSCCs activation, 3) neither ROCK- nor PI3K-dependent cascade is involved in NSCCs activation, and 4) G13 is involved in norepinephrine-induced arachidonic acid release in CHO-1A. norepinephrine; 1A-adrenergic receptor; nonselective cation channel; G13 protein; arachidonic acid release 相似文献
7.
BackgroundProtein-protein interaction (PPI) plays a core role in cellular functions. Massively parallel supercomputing systems have been actively developed over the past few years, which enable large-scale biological problems to be solved, such as PPI network prediction based on tertiary structures.ResultsWe have developed a high throughput and ultra-fast PPI prediction system based on rigid docking, “MEGADOCK”, by employing a hybrid parallelization (MPI/OpenMP) technique assuming usages on massively parallel supercomputing systems. MEGADOCK displays significantly faster processing speed in the rigid-body docking process that leads to full utilization of protein tertiary structural data for large-scale and network-level problems in systems biology. Moreover, the system was scalable as shown by measurements carried out on two supercomputing environments. We then conducted prediction of biological PPI networks using the post-docking analysis.ConclusionsWe present a new protein-protein docking engine aimed at exhaustive docking of mega-order numbers of protein pairs. The system was shown to be scalable by running on thousands of nodes. The software package is available at: http://www.bi.cs.titech.ac.jp/megadock/k/. 相似文献
8.
Linear B-cell epitopes are critically important for immunological applications, such as vaccine design, immunodiagnostic test, and antibody production, as well as disease diagnosis and therapy. The accurate identification of linear B-cell epitopes remains challenging despite several decades of research. In this work, we have developed a novel predictor, Identification of Linear B-cell Epitope (iLBE), by integrating evolutionary and sequence-based features. The successive feature vectors were optimized by a Wilcoxon-rank sum test. Then the random forest (RF) algorithm using the optimal consecutive feature vectors was applied to predict linear B-cell epitopes. We combined the RF scores by the logistic regression to enhance the prediction accuracy. iLBE yielded an area under curve score of 0.809 on the training dataset and outperformed other prediction models on a comprehensive independent dataset. iLBE is a powerful computational tool to identify the linear B-cell epitopes and would help to develop penetrating diagnostic tests. A web application with curated datasets for iLBE is freely accessible at http://kurata14.bio.kyutech.ac.jp/iLBE/. 相似文献
9.
-Syntrophin is a component of the dystrophin glycoprotein complex (DGC). It is firmly attached to the dystrophin cytoskeleton via a unique COOH-terminal domain and is associated indirectly with -dystroglycan, which binds to extracellular matrix laminin. Syntrophin contains two pleckstrin homology (PH) domains and one PDZ domain. Because PH domains of other proteins are known to bind the -subunits of the heterotrimeric G proteins, whether this is also a property of syntrophin was investigated. Isolated syntrophin from rabbit skeletal muscle binds bovine brain G-subunits in gel blot overlay experiments. Laminin-1-Sepharose or specific antibodies against syntrophin, - and -dystroglycan, or dystrophin precipitate a complex with G from crude skeletal muscle microsomes. Bacterially expressed syntrophin fusion proteins and truncation mutants allowed mapping of G binding to syntrophin's PDZ domain; this is a novel function for PDZ domains. When laminin-1 is bound, maximal binding of G s and G occurs and active G s, measured as GTP- 35S bound, decreases. Because intracellular Ca 2+ is elevated in Duchenne muscular dystrophy and G s is known to activate the dihydropyridine receptor Ca 2+ channel, whether laminin also altered intracellular Ca 2+ was investigated. Laminin-1 decreases active (GTP-S-bound) G s, and the Ca 2+ channel is inhibited by laminin-1. The laminin 1-chain globular domains 4 and 5 region, the region bound by DGC -dystroglycan, is sufficient to cause an effect, and an antibody that specifically blocks laminin binding to -dystroglycan inhibits G binding by syntrophin in C 2C 12 myotubes. These observations suggest that DGC is a matrix laminin, G protein-coupled receptor. Duchenne muscular dystrophy; protein G -subunit; pleckstrin homology domain 相似文献
10.
Context: We noticed paucity in exploiting solutol-based lipid nanocapsules in statins formulations though they carry all favorable properties that are needed for cancer passive targeting such as their small particle size, stealth properties, ability to highly accommodate lipophilic drugs, good internalization and P-gp pump inhibition. Objective: The aim of this study was to design and optimize new simvastatin drug delivery systems; lipid nanocapsules intended for administration through the intravenous route as potential treatment for breast cancer. Methods: Optimized nanocapsules were prepared by the phase-inversion method according to a D-optimal mixture design, characterized and assessed for their cytotoxicity. Results: Three successful models for particle size, polydispersity index (PDI) and percentage of drug released after 48 h were generated. The prepared lipid nanocapsules acquired spherical and homogenous morphology, good stability and tolerance to sterilization. The obtained release profiles demonstrated desired sustained release pattern. Furthermore, testing selected formulations on human breast cancer adenocarcinoma cells showed augmented cytotoxicity of simvastatin reaching low IC50 values as 1.4?±?0.02 μg/ml compared to the pure drug. Conclusion: The proposed lipid nanocapsules pose promising candidates as simvastatin carriers intended for the targeting of breast cancer. 相似文献
14.
To shed light on the mechanism of hydrophobic control in reactions of microbial tryptophanase the direct effect of the solvent hydrophobicity on affinities of amino acid inhibitors was first examined. Values of inhibition constants ( Ki) for a variety of amino acids were determined in 37.5% aqueous methanol, and no general correlation between the change of Ki, on passing from water to aqueous methanol, and amino acid hydrophobicity was found. The solvent effects on the separate stages of the external aldimine formation ( KD) and deprotonation to form a quinonoid intermediate ( Kq) were determined for the reactions of tryptophanase with 2-oxindolyl-
-alanine and
-alanine by stopped-flow technique. For 2-oxindolyl-
-alanine, which is a close transition-state analogue for the enzyme reaction with natural substrate, the decrease in the affinity in aqueous methanol is associated exclusively with the α-proton abstraction stage but not with the preceding formation of external aldimine. We conclude that the environment of amino acid side chains in the active site cannot be considered to be permanently hydrophobic irrespective of the bound amino acid. We suggest that complexes of tryptophanase with amino acids may exist either in a hydrophobic, presumably “closed”, conformation, where bound amino acids are isolated from the solvent, or in an accesible to solvent, “open”, conformation, depending on the structure of the bound amino acid and stage of the catalytic mechanism. For 2-oxindolyl-
-alanine the transfer from an open to a closed conformation probably accompanies deprotonation of the external aldimine. The change of the active site hydrophobicity may provide an efficient way of modulating the relative acid–base properties of the catalytic groups to ensure the movement of protons in the “correct” direction depending on the elementary stage of catalysis. 相似文献
15.
Context: Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU). Objective: To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility. Materials and methods: Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects. Results: Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects. Conclusion: Polymorphisms in IL21 may be associated with sepsis risk. 相似文献
16.
Detecting biclusters from expression data is useful, since biclusters are coexpressed genes under only part of all given experimental conditions. We present a software called SiBIC, which from a given expression dataset, first exhaustively enumerates biclusters, which are then merged into rather independent biclusters, which finally are used to generate gene set networks, in which a gene set assigned to one node has coexpressed genes. We evaluated each step of this procedure: 1) significance of the generated biclusters biologically and statistically, 2) biological quality of merged biclusters, and 3) biological significance of gene set networks. We emphasize that gene set networks, in which nodes are not genes but gene sets, can be more compact than usual gene networks, meaning that gene set networks are more comprehensible. SiBIC is available at http://utrecht.kuicr.kyoto-u.ac.jp:8080/miami/faces/index.jsp. 相似文献
17.
Heterotrimeric G i proteins may play a role in lipopolysaccharide (LPS)-activated signaling through Toll-like receptor 4 (TLR4), leading to inflammatory mediator production. Although LPS is a TLR4 ligand, the gram-positive bacterium Staphylococcus aureus (SA) is a TLR2 ligand, and group B streptococci (GBS) are neither TLR2 nor TLR4 ligands but are MyD88 dependent. We hypothesized that genetic deletion of G i proteins would alter mediator production induced by LPS and gram-positive bacterial stimulation. We examined genetic deletion of G i2 or G i1/3 protein in G i2-knockout (G i2/) or G i1/3-knockout (G i1/3/) mice. LPS-, heat-killed SA-, or GBS-induced mediator production in splenocytes or peritoneal macrophages (M) was investigated. There were significant increases in LPS-, SA-, and GBS-induced production of TNF- and IFN- in splenocytes from G i2/ mice compared with wild-type (WT) mice. Also, LPS-induced TNF- was increased in splenocytes from G i1/3/ mice. In contrast to splenocytes, LPS-, SA-, and GBS-induced TNF-, IL-10, and thromboxane B 2 (TxB 2) production was decreased in M harvested from G i2/ mice. Also, LPS-induced production of IL-10 and TxB 2 was decreased in M from G i1/3/ mice. In subsequent in vivo studies, TNF- levels after LPS challenge were significantly greater in G i2/ mice than in WT mice. Also, myeloperoxidase activity, a marker of tissue neutrophil infiltration, was significantly increased in the gut and lung of LPS-treated G i2/ mice compared with WT mice. These data suggest that G i proteins differentially regulate murine TLR-mediated inflammatory cytokine production in a cell-specific manner in response to both LPS and gram-positive microbial stimuli. G i protein-deficient mice; endotoxin; group B streptococci; Staphylococcus aureus; Toll-like receptors 相似文献
18.
We examined expression of sphingosine 1-phosphate (S1P) receptors and sphingosine kinase (SPK) in gastric smooth muscle cells and characterized signaling pathways mediating S1P-induced 20-kDa myosin light chain (MLC 20) phosphorylation and contraction. RT-PCR demonstrated expression of SPK1 and SPK2 and S1P 1 and S1P 2 receptors. S1P activated G q, G 13, and all G i isoforms and stimulated PLC-1, PLC-3, and Rho kinase activities. PLC- activity was partially inhibited by pertussis toxin (PTX), G or G q antibody, PLC-1 or PLC-3 antibody, and by expression of G q or G i minigene, and was abolished by a combination of antibodies or minigenes. S1P-stimulated Rho kinase activity was partially inhibited by expression of G 13 or G q minigene and abolished by expression of both. S1P stimulated Ca 2+ release that was inhibited by U-73122 and heparin and induced concentration-dependent contraction of smooth muscle cells (EC 50 1 nM). Initial contraction and MLC 20 phosphorylation were abolished by U-73122 and MLC kinase (MLCK) inhibitor ML-9. Initial contraction was also partially inhibited by PTX and G q or G antibody and abolished by a combination of both antibodies. In contrast, sustained contraction and MLC 20 phosphorylation were partially inhibited by a PKC or Rho kinase inhibitor (bisindolylmaleimide and Y-27632) and abolished by a combination of both inhibitors but not affected by U-73122 or ML-9. These results indicate that S1P induces 1) initial contraction mediated by S1P 2 and S1P 1 involving concurrent activation of PLC-1 and PLC-3 via G q and G i, respectively, resulting in inositol 1,4,5-trisphosphate-dependent Ca 2+ release and MLCK-mediated MLC 20 phosphorylation, and 2) sustained contraction exclusively mediated by S1P 2 involving activation of RhoA via G q and G 13, resulting in Rho kinase- and PKC-dependent MLC 20 phosphorylation. muscle contraction; signal transduction 相似文献
19.
Screening of ligand molecules to target proteins using computer-aided docking is a critical step in rational drug discovery. Based on this circumstance, we
attempted to develop a virtual screening application system, named VSDK Virtual Screening by Docking, which can function under the Windows platform. This is
a user-friendly, flexible, and versatile tool which can be used by users who are familiar with Windows OS. The virtual screening performance was tested for an
arbitrarily-selected receptor, FGFR tyrosine kinase (pdb code: 1agw), by using ligands downloaded from ZINC database with its grid size of x,y,z = 30,30,30 and
run number of 10. It took 90 minutes for 100 molecules for this virtual screening. VSDK is freely available at the designated URL, and a simplified manual can be
downloaded from VSDK home page. This tool will have a more challenging scope and achievement as the computer speed and accuracy are increased and secured
in the future. AvailabilityThe database is available for free at http://www.pharm.kobegakuin.ac.jp/˜akaho/english_top.html 相似文献
20.
The Ca 2+-sensing receptor (CaR) couples to multiple G proteins involved in distinct signaling pathways: G i to inhibit the activity of adenylyl cyclase and activate ERK, G q to stimulate phospholipase C and phospholipase A 2, and G to stimulate phosphatidylinositol 3-kinase. To determine whether the receptor also couples to G 12/13, we investigated the signaling pathway by which the CaR regulates phospholipase D (PLD), a known G 12/13 target. We established Madin-Darby canine kidney (MDCK) cell lines that stably overexpress the wild-type CaR (CaR WT) or the nonfunctional mutant CaR R796W as a negative control, prelabeled these cells with [ 3H]palmitic acid, and measured CaR-stimulated PLD activity as the formation of [ 3H]phosphatidylethanol (PEt). The formation of [ 3H]PEt increased in a time-dependent manner in the cells that overexpress the CaR WT but not the CaR R796W. Treatment of the cells with C 3 exoenzyme inhibited PLD activity, which indicates that the CaR activates the Rho family of small G proteins, targets of G 12/13. To determine which G protein(s) the CaR couples to in order to activate Rho and PLD, we pretreated the cells with pertussis toxin to inactivate G i or coexpressed regulators of G protein-signaling (RGS) proteins to attenuate G protein signaling (RGS4 for G i and G q, and a p115RhoGEF construct containing the RGS domain for G 12/13). Overexpression of p115RhoGEF-RGS in the MDCK cells that overexpress CaR WT inhibited extracellular Ca 2+-stimulated PLD activity, but pretreatment of cells with pertussis toxin and overexpression of RGS4 were without effect. The involvement of other signaling components such as protein kinase C, ADP-ribosylation factor, and phosphatidylinositol biphosphate was excluded. These findings demonstrate that the CaR couples to G 12/13 to regulate PLD via a Rho-dependent mechanism and does so independently of G i and G q. This suggests that the CaR may regulate cytoskeleton via G 12/13, Rho, and PLD. calcium-sensing receptor; G proteins; RGS proteins 相似文献
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