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Sample records for peptidyl transferase centre

  1. The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.

    Science.gov (United States)

    Poulsen, S M; Karlsson, M; Johansson, L B; Vester, B

    2001-09-01

    The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.

  2. The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome

    DEFF Research Database (Denmark)

    Poulsen, S M; Karlsson, M; Johansson, L B

    2001-01-01

    The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs...... centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous...... results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer....

  3. Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin

    Directory of Open Access Journals (Sweden)

    Fucini Paola

    2004-04-01

    Full Text Available Abstract Background The bacterial ribosome is a primary target of several classes of antibiotics. Investigation of the structure of the ribosomal subunits in complex with different antibiotics can reveal the mode of inhibition of ribosomal protein synthesis. Analysis of the interactions between antibiotics and the ribosome permits investigation of the specific effect of modifications leading to antimicrobial resistances. Streptogramins are unique among the ribosome-targeting antibiotics because they consist of two components, streptogramins A and B, which act synergistically. Each compound alone exhibits a weak bacteriostatic activity, whereas the combination can act bactericidal. The streptogramins A display a prolonged activity that even persists after removal of the drug. However, the mode of activity of the streptogramins has not yet been fully elucidated, despite a plethora of biochemical and structural data. Results The investigation of the crystal structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with the clinically relevant streptogramins quinupristin and dalfopristin reveals their unique inhibitory mechanism. Quinupristin, a streptogramin B compound, binds in the ribosomal exit tunnel in a similar manner and position as the macrolides, suggesting a similar inhibitory mechanism, namely blockage of the ribosomal tunnel. Dalfopristin, the corresponding streptogramin A compound, binds close to quinupristin directly within the peptidyl transferase centre affecting both A- and P-site occupation by tRNA molecules. Conclusions The crystal structure indicates that the synergistic effect derives from direct interaction between both compounds and shared contacts with a single nucleotide, A2062. Upon binding of the streptogramins, the peptidyl transferase centre undergoes a significant conformational transition, which leads to a stable, non-productive orientation of the universally conserved U2585. Mutations of this r

  4. Antibiotic inhibition of the movement of tRNA substrates through a peptidyl transferase cavity

    DEFF Research Database (Denmark)

    Porse, B T; Rodriguez-Fonseca, C; Leviev, I

    1996-01-01

    The present review attempts to deal with movement of tRNA substrates through the peptidyl transferase centre on the large ribosomal subunit and to explain how this movement is interrupted by antibiotics. It builds on the concept of hybrid tRNA states forming on ribosomes and on the observed movem...

  5. Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates.

    Science.gov (United States)

    Pringle, Märit; Poehlsgaard, Jacob; Vester, Birte; Long, Katherine S

    2004-12-01

    The pleuromutilin antibiotic tiamulin binds to the ribosomal peptidyl transferase centre. Three groups of Brachyspira spp. isolates with reduced tiamulin susceptibility were analysed to define resistance mechanisms to the drug. Mutations were identified in genes encoding ribosomal protein L3 and 23S rRNA at positions proximal to the peptidyl transferase centre. In two groups of laboratory-selected mutants, mutations were found at nucleotide positions 2032, 2055, 2447, 2499, 2504 and 2572 of 23S rRNA (Escherichia coli numbering) and at amino acid positions 148 and 149 of ribosomal protein L3 (Brachyspira pilosicoli numbering). In a third group of clinical B. hyodysenteriae isolates, only a single mutation at amino acid 148 of ribosomal protein L3 was detected. Chemical footprinting experiments show a reduced binding of tiamulin to ribosomal subunits from mutants with decreased susceptibility to the drug. This reduction in drug binding is likely the resistance mechanism for these strains. Hence, the identified mutations located near the tiamulin binding site are predicted to be responsible for the resistance phenotype. The positions of the mutated residues relative to the bound drug advocate a model where the mutations affect tiamulin binding indirectly through perturbation of nucleotide U2504.

  6. Mapping important nucleotides in the peptidyl transferase centre of 23 S rRNA using a random mutagenesis approach

    DEFF Research Database (Denmark)

    Porse, B T; Garrett, R A

    1995-01-01

    Random mutations were generated in the lower half of the peptidyl transferase loop in domain V of 23 S rRNA from Escherichia coli using a polymerase chain reaction (PCR) approach, a rapid procedure for identifying mutants and a plasmid-based expression system. The effects of 21 single-site mutati...

  7. Interaction of Pleuromutilin Derivatives with the Ribosomal Peptidyl Transferase Center

    Science.gov (United States)

    Long, Katherine S.; Hansen, Lykke H.; Jakobsen, Lene; Vester, Birte

    2006-01-01

    Tiamulin is a pleuromutilin antibiotic that is used in veterinary medicine. The recently published crystal structure of a tiamulin-50S ribosomal subunit complex provides detailed information about how this drug targets the peptidyl transferase center of the ribosome. To promote rational design of pleuromutilin-based drugs, the binding of the antibiotic pleuromutilin and three semisynthetic derivatives with different side chain extensions has been investigated using chemical footprinting. The nucleotides A2058, A2059, G2505, and U2506 are affected in all of the footprints, suggesting that the drugs are similarly anchored in the binding pocket by the common tricyclic mutilin core. However, varying effects are observed at U2584 and U2585, indicating that the side chain extensions adopt distinct conformations within the cavity and thereby affect the rRNA conformation differently. An Escherichia coli L3 mutant strain is resistant to tiamulin and pleuromutilin, but not valnemulin, implying that valnemulin is better able to withstand an altered rRNA binding surface around the mutilin core. This is likely due to additional interactions made between the valnemulin side chain extension and the rRNA binding site. The data suggest that pleuromutilin drugs with enhanced antimicrobial activity may be obtained by maximizing the number of interactions between the side chain moiety and the peptidyl transferase cavity. PMID:16569865

  8. Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center

    DEFF Research Database (Denmark)

    Long, K. S.; Hansen, L. K.; Jakobsen, L.

    2006-01-01

    Tiamulin is a pleuromutilin antibiotic that is used in veterinary medicine. The recently published crystal structure of a tiamulin-50S ribosomal subunit complex provides detailed information about how this drug targets the peptidyl transferase center of the ribosome. To promote rational design...... mutant strain is resistant to tiamulin and pleuromutilin, but not valnemulin, implying that valnemulin is better able to withstand an altered rRNA binding surface around the mutilin core. This is likely due to additional interactions made between the valnemulin side chain extension and the rRNA binding...

  9. Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3.

    Science.gov (United States)

    Bøsling, Jacob; Poulsen, Susan M; Vester, Birte; Long, Katherine S

    2003-09-01

    The antibiotic tiamulin targets the 50S subunit of the bacterial ribosome and interacts at the peptidyl transferase center. Tiamulin-resistant Escherichia coli mutants were isolated in order to elucidate mechanisms of resistance to the drug. No mutations in the rRNA were selected as resistance determinants using a strain expressing only a plasmid-encoded rRNA operon. Selection in a strain with all seven chromosomal rRNA operons yielded a mutant with an A445G mutation in the gene coding for ribosomal protein L3, resulting in an Asn149Asp alteration. Complementation experiments and sequencing of transductants demonstrate that the mutation is responsible for the resistance phenotype. Chemical footprinting experiments show a reduced binding of tiamulin to mutant ribosomes. It is inferred that the L3 mutation, which points into the peptidyl transferase cleft, causes tiamulin resistance by alteration of the drug-binding site. This is the first report of a mechanism of resistance to tiamulin unveiled in molecular detail.

  10. Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

    Energy Technology Data Exchange (ETDEWEB)

    Osterman, Ilya A.; Khabibullina, Nelli F.; Komarova, Ekaterina S.; Kasatsky, Pavel; Kartsev, Victor G.; Bogdanov, Alexey A.; Dontsova, Olga A.; Konevega, Andrey L.; Sergiev, Petr V.; Polikanov, Yury S. (InterBioScreen); (UIC); (MSU-Russia); (Kurchatov)

    2017-05-13

    The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.

  11. Resistance to the Peptidyl Transferase Inhibitor Tiamulin Caused by Mutation of Ribosomal Protein L3

    OpenAIRE

    Bøsling, Jacob; Poulsen, Susan M.; Vester, Birte; Long, Katherine S.

    2003-01-01

    The antibiotic tiamulin targets the 50S subunit of the bacterial ribosome and interacts at the peptidyl transferase center. Tiamulin-resistant Escherichia coli mutants were isolated in order to elucidate mechanisms of resistance to the drug. No mutations in the rRNA were selected as resistance determinants using a strain expressing only a plasmid-encoded rRNA operon. Selection in a strain with all seven chromosomal rRNA operons yielded a mutant with an A445G mutation in the gene coding for ri...

  12. UV-induced modifications in the peptidyl transferase loop of 23S rRNA dependent on binding of the streptogramin B antibiotic, pristinamycin IA

    DEFF Research Database (Denmark)

    Porse, B T; Kirillov, S V; Awayez, M J

    1999-01-01

    The naturally occurring streptogramin B antibiotic, pristinamycin IA, which inhibits peptide elongation, can produce two modifications in 23S rRNA when bound to the Escherichia coli 70S ribosome and irradiated at 365 nm. Both drug-induced effects map to highly conserved nucleotides within...... in the latter modification to A2062/C2063. Pristinamycin IA can also produce a modification on binding to deproteinized, mature 23S rRNA, at position U2500/C2501. The same modification occurs on an approximately 37-nt fragment, encompassing positions approximately 2496-2532 of the peptidyl transferase loop...... the sequence Cm-C-U-C-G-m2A-psi-G2505 are important for pristinamycin IA binding and/or the antibiotic-dependent modification of 23S rRNA....

  13. Mutations in 23S rRNA at the Peptidyl Transferase Center and Their Relationship to Linezolid Binding and Cross-Resistance

    DEFF Research Database (Denmark)

    Long, Katherine; Munck, Christian

    2010-01-01

    The oxazolidinone antibiotic linezolid targets the peptidyl transferase center (PTC) on the bacterial ribosome. Thirteen single and four double 23S rRNA mutations were introduced into a Mycobacterium smegmatis strain with a single rRNA operon. Converting bacterial base identity by single mutations...... at positions 2032, 2453, and 2499 to human cytosolic base identity did not confer significantly reduced susceptibility to linezolid. The largest decrease in linezolid susceptibility for any of the introduced single mutations was observed with the G2576U mutation at a position that is 7.9 Å from linezolid....... Smaller decreases were observed with the A2503G, U2504G, and G2505A mutations at nucleotides proximal to linezolid, showing that the degree of resistance conferred is not simply inversely proportional to the nucleotide-drug distance. The double mutations G2032A-C2499A, G2032A-U2504G, C2055A-U2504G, and C...

  14. A SAM-dependent methyltransferase cotranscribed with arsenate reductase alters resistance to peptidyl transferase center-binding antibiotics in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Singh, Sudhir; Singh, Chhaya; Tripathi, Anil Kumar

    2014-05-01

    The genome of Azospirillum brasilense harbors a gene encoding S-adenosylmethionine-dependent methyltransferase, which is located downstream of an arsenate reductase gene. Both genes are cotranscribed and translationally coupled. When they were cloned and expressed individually in an arsenate-sensitive strain of Escherichia coli, arsenate reductase conferred tolerance to arsenate; however, methyltransferase failed to do so. Sequence analysis revealed that methyltransferase was more closely related to a PrmB-type N5-glutamine methyltransferase than to the arsenate detoxifying methyltransferase ArsM. Insertional inactivation of prmB gene in A. brasilense resulted in an increased sensitivity to chloramphenicol and resistance to tiamulin and clindamycin, which are known to bind at the peptidyl transferase center (PTC) in the ribosome. These observations suggested that the inability of prmB:km mutant to methylate L3 protein might alter hydrophobicity in the antibiotic-binding pocket of the PTC, which might affect the binding of chloramphenicol, clindamycin, and tiamulin differentially. This is the first report showing the role of PrmB-type N5-glutamine methyltransferases in conferring resistance to tiamulin and clindamycin in any bacterium.

  15. Affinity labelling of ribosomes from the livers of different vertebrates by 2-nitro-4-azidobenzoyl-Phe-tRNA

    International Nuclear Information System (INIS)

    Stahl, J.; Boehm, H.; Voderberg, M.

    1981-01-01

    Ribosomal protein L 10 from the livers of trout, hen, and rat was found to be the main target for 2-nitro-4-azidobenzoyl-Phe-tRNA in affinity labelling experiments. Therefore, despite somewhat different electrophoretic mobilities, this protein seems to be involved in the organization of the peptidyl transferase centre in ribosomes of various vertebrates. (author)

  16. Peptidylation for the determination of low-molecular-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Tang, Feng; Cen, Si-Ying; He, Huan; Liu, Yi; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-05-23

    Determination of low-molecular-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been a great challenge in the analytical research field. Here we developed a universal peptide-based derivatization (peptidylation) strategy for the sensitive analysis of low-molecular-weight compounds by MALDI-TOF-MS. Upon peptidylation, the molecular weights of target analytes increase, thus avoiding serious matrix ion interference in the low-molecular-weight region in MALDI-TOF-MS. Since peptides typically exhibit good signal response during MALDI-TOF-MS analysis, peptidylation endows high detection sensitivities of low-molecular-weight analytes. As a proof-of-concept, we analyzed low-molecular-weight compounds of aldehydes and thiols by the developed peptidylation strategy. Our results showed that aldehydes and thiols can be readily determined upon peptidylation, thus realizing the sensitive and efficient determination of low-molecular-weight compounds by MALDI-TOF-MS. Moreover, target analytes also can be unambiguously detected in biological samples using the peptidylation strategy. The established peptidylation strategy is a universal strategy and can be extended to the sensitive analysis of various low-molecular-weight compounds by MALDI-TOF-MS, which may be potentially used in areas such as metabolomics.

  17. Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors.

    Science.gov (United States)

    Shen, Gang; Zhu, Jinge; Simpson, Anthony M; Pei, Dehua

    2008-05-15

    Macrocyclic peptidyl hydroxamates were designed, synthesized, and evaluated as peptide deformylase (PDF) inhibitors. The most potent compound exhibited tight, slow-binding inhibition of Escherichia coli PDF (K(I)(*)=4.4 nM) and had potent antibacterial activity against Gram-positive bacterium Bacillus subtilis (MIC=2-4 microg/mL).

  18. Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors

    DEFF Research Database (Denmark)

    Storgaard, Morten; Henriksen, Signe Teuber; Zaragoza, Florencio

    2011-01-01

    Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia...

  19. Identification of the S-transferase like superfamily bacillithiol transferases encoded by Bacillus subtilis

    Science.gov (United States)

    Perera, Varahenage R.; Lapek, John D.; Newton, Gerald L.; Gonzalez, David J.; Pogliano, Kit

    2018-01-01

    Bacillithiol is a low molecular weight thiol found in Firmicutes that is analogous to glutathione, which is absent in these bacteria. Bacillithiol transferases catalyze the transfer of bacillithiol to various substrates. The S-transferase-like (STL) superfamily contains over 30,000 putative members, including bacillithiol transferases. Proteins in this family are extremely divergent and are related by structural rather than sequence similarity, leaving it unclear if all share the same biochemical activity. Bacillus subtilis encodes eight predicted STL superfamily members, only one of which has been shown to be a bacillithiol transferase. Here we find that the seven remaining proteins show varying levels of metal dependent bacillithiol transferase activity. We have renamed the eight enzymes BstA-H. Mass spectrometry and gene expression studies revealed that all of the enzymes are produced to varying levels during growth and sporulation, with BstB and BstE being the most abundant and BstF and BstH being the least abundant. Interestingly, several bacillithiol transferases are induced in the mother cell during sporulation. A strain lacking all eight bacillithiol transferases showed normal growth in the presence of stressors that adversely affect growth of bacillithiol-deficient strains, such as paraquat and CdCl2. Thus, the STL bacillithiol transferases represent a new group of proteins that play currently unknown, but potentially significant roles in bacillithiol-dependent reactions. We conclude that these enzymes are highly divergent, perhaps to cope with an equally diverse array of endogenous or exogenous toxic metabolites and oxidants. PMID:29451913

  20. Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

    Directory of Open Access Journals (Sweden)

    Mary C. Hames

    2013-11-01

    Full Text Available Bacterial Pth1 is essential for viability. Pth1 cleaves the ester bond between the peptide and nucleotide of peptidyl-tRNA generated from aborted translation, expression of mini-genes, and short ORFs. We have determined the shape of the Pth1:peptidyl-tRNA complex using small angle neutron scattering. Binding of piperonylpiperazine, a small molecule constituent of a combinatorial synthetic library common to most compounds with inhibitory activity, was mapped to Pth1 via NMR spectroscopy. We also report computational docking results, modeling piperonylpiperazine binding based on chemical shift perturbation mapping. Overall these studies promote Pth1 as a novel antibiotic target, contribute to understanding how Pth1 interacts with its substrate, advance the current model for cleavage, and demonstrate feasibility of small molecule inhibition.

  1. Transferases in Polymer Chemistry

    NARCIS (Netherlands)

    van der Vlist, Jeroen; Loos, Katja; Palmans, ARA; Heise, A

    2010-01-01

    Transferases are enzymes that catalyze reactions in which a group is transferred from one compound to another. This makes these enzymes ideal catalysts for polymerization reactions. In nature, transferases are responsible for the synthesis of many important natural macromolecules. In synthetic

  2. Hibiscus cannabinus feruloyl-coa:monolignol transferase

    Science.gov (United States)

    Wilkerson, Curtis; Ralph, John; Withers, Saunia; Mansfield, Shawn D.

    2016-11-15

    The invention relates to isolated nucleic acids encoding a feruloyl-CoA:monolignol transferase and feruloyl-CoA:monolignol transferase enzymes. The isolated nucleic acids and/or the enzymes enable incorporation of monolignol ferulates into the lignin of plants, where such monolignol ferulates include, for example, p-coumaryl ferulate, coniferyl ferulate, and/or sinapyl ferulate. The invention also includes methods and plants that include nucleic acids encoding a feruloyl-CoA:monolignol transferase enzyme and/or feruloyl-CoA:monolignol transferase enzymes.

  3. An ATP-dependent ligase with substrate flexibility involved in assembly of the peptidyl nucleoside antibiotic polyoxin

    Science.gov (United States)

    Polyoxin (POL) is an unusual nucleoside antibiotic, in which peptidyl moiety and nucleoside skeleton are linked by an amide bond. However, their biosynthesis remains poorly understood. Here, we report the deciphering of PolG as an ATP-dependent ligase responsible for the assembly of POL. A polG muta...

  4. Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons

    DEFF Research Database (Denmark)

    Macvanin, Mirjana; Gonzalez de Valdivia, Ernesto I; Ardell, David H

    2007-01-01

    -peptide-encoding sequence, we asked whether the codons UGG and GGG, which are known to promote peptidyl-tRNA drop-off at early positions in mRNA, would result in a phenotype of erythromycin resistance if located after this sequence. We find that UGG or GGG, at either position +4 or +5, without a following stop codon......, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin...... resistance. Thus, the drop-off event on GGG or UGG codons occurs after incorporation of the corresponding amino acid into the growing peptide chain. Drop-off gives rise to a peptidyl-tRNA where the peptide moiety functionally mimics a minigene peptide product of the type previously associated...

  5. Myristoylated proteins and peptidyl myristoyltransferase

    International Nuclear Information System (INIS)

    Marchildon, G.A.

    1986-01-01

    The distribution and intracellular locations of myristoylated proteins have been examined in cultured cells. Incubating a variety of cells in minimal medium containing / 3 H/ myristate led to the incorporation of labeled myristate into as many as twenty-five different intracellular proteins. The incorporation increased linearly with time for up to six hours and then increased more slowly for an additional ten hours. The chemical stability indicated that the attachment was covalent and excluded nucleophile-labile bonds such as thioesters. Fluorographs of proteins modified by / 3 H/ myristate and resolved on gradient SDS-PAGE showed patterns that differed from cell type to cell type. To examine the intracellular locations of the myristate-labeled proteins, cells were isotonically subfractionated. Most of the myristate-labeled proteins remained in the high speed supernatant devoid of microsomal membranes. This indicated that the myristate modification in itself is not sufficient to serve as an anchor for membrane association. Myristate labeled catalytic subunit of the cyclic AMP dependent protein kinase was specifically immunoprecipitated from an aliquot of the high speed supernatant proteins. However, the prominent tyrosine protein kinase of the murine lymphoma cell line LSTRA, pp56/sup lstra/, also incorporated myristate and was specifically immunoprecipitated from the high speed pellet (particulate) fraction of labeled LSTRA cells. To begin to understand the biochemical mechanism of myristate attachment to protein. The authors partially purified and characterized the peptidyl myristoyltransferase from monkey liver. Recovery of enzymatic activity was 69%

  6. The Order Bacillales Hosts Functional Homologs of the Worrisome cfr Antibiotic Resistance Gene

    DEFF Research Database (Denmark)

    Hansen, Lykke H.; Planellas, Mercè H.; Long, Katherine S.

    2012-01-01

    The cfr gene encodes the Cfr methyltransferase that methylates a single adenine in the peptidyl transferase region of bacterial ribosomes. The methylation provides resistance to several classes of antibiotics that include drugs of clinical and veterinary importance. This paper describes a first...

  7. The Cfr rRNA methyltransferase confers resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics

    DEFF Research Database (Denmark)

    Long, K. S.; Poehlsgaard, Jacob; Kehrenberg, C.

    2006-01-01

    to overlapping sites at the peptidyl transferase center that abut nucleotide A2503, is perturbed upon Cfr-mediated methylation. Decreased drug binding to Cfr-methylated ribosomes has been confirmed by footprinting analysis. No other rRNA methyltransferase is known to confer resistance to five chemically distinct...

  8. Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease

    Science.gov (United States)

    Kim, Yunjeong; Mandadapu, Sivakoteswara Rao; Groutas, William C.; Chang, Kyeong-Ok

    2012-01-01

    Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against feline coronaviruses in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC50 in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in cell culture systems. PMID:23219425

  9. SIKLODEKSTRIN GLIKOSIL TRANSFERASE DAN PEMANFAATANNYA DALAM INDUSTRI [Cyclodextrin Glycosyl Transferase and its application in industries

    Directory of Open Access Journals (Sweden)

    Budiasih Wahyuntari

    2005-12-01

    Full Text Available Cyclodextrin glycosyl transferase (CGT-ase is mainly produced by Bacilli. Systematical name of the enzyme is E.C. 2.4.1.19 a-1,4 glucan-4-glycosyl transferase. The enzyme catalyzes hydrolysis of starch intramolecular, and intermolecular transglycosylation of a-1,4, glucan chains. Cyclodextrins are a-1,4 linked cyclic oligosaccharides resulting from enzymatic degradation of starch by cyclodextrin glycosyl transferase through untramolecular transglycosylation. The major cyclodextrins are made up of 6, 7 and 8 glucopyranose units which are known as a-, b-, and y-cyclodextrin. All CGT-ase catalyze three kinds of cyclodextrins, the proportion of the cyclodextrins depends on the enzyme source and reaction conditions. The intermolecular transglycosylation ability of the enzyme has been applied in transfering glycosyl residues into suitable acceptor. Transglycosylation by the enzymes have been tested to improve solubility of some flavonoids and to favor precipitation ci some glycosides.

  10. Helicobacter pylori Peptidyl Prolyl Isomerase Expression Is Associated with the Severity of Gastritis.

    Science.gov (United States)

    Oghalaie, Akbar; Saberi, Samaneh; Esmaeili, Maryam; Ebrahimzadeh, Fatemeh; Barkhordari, Farzaneh; Ghamarian, Abdolreza; Tashakoripoor, Mohammad; Abdirad, Afshin; Eshagh Hosseini, Mahmoud; Khalaj, Vahid; Mohammadi, Marjan

    2016-12-01

    Helicobacter pylori secretory peptidyl prolyl isomerase, HP0175, is progressively identified as a pro-inflammatory and pro-carcinogenic protein, which serves to link H. pylori infection to its more severe clinical outcomes. Here, we have analyzed host HP0175-specific antibody responses in relation to the severity of gastritis. The HP0175 gene fragment was PCR-amplified, cloned, expressed and purified by Ni-NTA affinity chromatography. Serum antigen-specific antibody responses of non-ulcer dyspeptic patients (N = 176) against recombinant HP0175 were detected by western blotting. The infection status of these subjects was determined by rapid urease test, culture, histology, and serology. The grade of inflammation and stage of atrophy were scored blindly according to the OLGA staging system. The recombinant HP0175 (rHP0175) was expressed as a ~35 kDa protein and its identity was confirmed by western blotting using anti-6X His tag antibody and pooled H. pylori-positive sera. Serum IgG antibodies against rHP0175 segregated our patients into two similar-sized groups of sero-positives (90/176, 51.1 %) and sero-negatives (86/176, 48.9 %). The former presented with higher grades of gastric inflammation (OR = 4.4, 95 % CI = 1.9-9.9, P = 0.001) and stages of gastric atrophy (OR = 18.3, 95 %CI = 1.4-246.6, P = 0.028). Our findings lend further support to the pro-inflammatory nature of H. pylori peptidyl prolyl isomerase (HP0175) and recommends this antigen as a non-invasive serum biomarker of the severity of H. pylori-associated gastritis.

  11. Human cyclophilin B: A second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence

    International Nuclear Information System (INIS)

    Price, E.R.; Zydowsky, L.D.; Jin, Mingjie; Baker, C.H.; McKeon, F.D.; Walsh, C.T.

    1991-01-01

    The authors report the cloning and characterization of a cDNA encoding a second human cyclosporin A-binding protein (hCyPB). Homology analyses reveal that hCyPB is a member of the cyclophilin B (CyPB) family, which includes yeast CyPB, Drosophila nina A, and rat cyclophilin-like protein. This family is distinguished from the cyclophilin A (CyPA) family by the presence of endoplasmic reticulum (ER)-directed signal sequences. hCyPB has a hydrophobic leader sequence not found in hCyPA, and its first 25 amino acids are removed upon expression in Escherichia coli. Moreover, they show that hCyPB is a peptidyl-prolyl cis-trans isomerase which can be inhibited by cyclosporin A. These observations suggest that other members of the CyPB family will have similar enzymatic properties. Sequence comparisons of the CyPB proteins show a central, 165-amino acid peptidyl-prolyl isomerase and cyclosprorin A-binding domain, flanked by variable N-terminal and C-terminal domains. These two variable regions may impart compartmental specificity and regulation to this family of cyclophilin proteins containing the conserved core domain. Northern blot analyses show that hCyPB mRNA is expressed in the Jurkat T-cell line, consistent with its possible target role in cyclosporin A-mediated immunosuppression

  12. Problem-Based Test: Functional Analysis of Mutant 16S rRNAs

    Science.gov (United States)

    Szeberenyi, Jozsef

    2010-01-01

    Terms to be familiar with before you start to solve the test: ribosome, ribosomal subunits, antibiotics, point mutation, 16S, 5S, and 23S rRNA, Shine-Dalgarno sequence, mRNA, tRNA, palindrome, hairpin, restriction endonuclease, fMet-tRNA, peptidyl transferase, initiation, elongation, termination of translation, expression plasmid, transformation,…

  13. Structural and Biochemical Characterization of the Human Cyclophilin Family of Peptidyl-Prolyl Isomerases

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Tara L.; Walker, John R.; Campagna-Slater, Valérie; Finerty, Jr., Patrick J.; Paramanathan, Ragika; Bernstein, Galina; MacKenzie, Farrell; Tempel, Wolfram; Ouyang, Hui; Lee, Wen Hwa; Eisenmesser, Elan Z.; Dhe-Paganon, Sirano (Toronto); (Colorado)

    2011-12-14

    Peptidyl-prolyl isomerases catalyze the conversion between cis and trans isomers of proline. The cyclophilin family of peptidyl-prolyl isomerases is well known for being the target of the immunosuppressive drug cyclosporin, used to combat organ transplant rejection. There is great interest in both the substrate specificity of these enzymes and the design of isoform-selective ligands for them. However, the dearth of available data for individual family members inhibits attempts to design drug specificity; additionally, in order to define physiological functions for the cyclophilins, definitive isoform characterization is required. In the current study, enzymatic activity was assayed for 15 of the 17 human cyclophilin isomerase domains, and binding to the cyclosporin scaffold was tested. In order to rationalize the observed isoform diversity, the high-resolution crystallographic structures of seven cyclophilin domains were determined. These models, combined with seven previously solved cyclophilin isoforms, provide the basis for a family-wide structure:function analysis. Detailed structural analysis of the human cyclophilin isomerase explains why cyclophilin activity against short peptides is correlated with an ability to ligate cyclosporin and why certain isoforms are not competent for either activity. In addition, we find that regions of the isomerase domain outside the proline-binding surface impart isoform specificity for both in vivo substrates and drug design. We hypothesize that there is a well-defined molecular surface corresponding to the substrate-binding S2 position that is a site of diversity in the cyclophilin family. Computational simulations of substrate binding in this region support our observations. Our data indicate that unique isoform determinants exist that may be exploited for development of selective ligands and suggest that the currently available small-molecule and peptide-based ligands for this class of enzyme are insufficient for isoform

  14. Effects of peptidyl-prolyl isomerase 1 depletion in animal models of prion diseases.

    Science.gov (United States)

    Legname, Giuseppe; Virgilio, Tommaso; Bistaffa, Edoardo; De Luca, Chiara Maria Giulia; Catania, Marcella; Zago, Paola; Isopi, Elisa; Campagnani, Ilaria; Tagliavini, Fabrizio; Giaccone, Giorgio; Moda, Fabio

    2018-04-20

    Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1 +/+ ), hemizygous (Pin1 +/- ) or knock-out (Pin1 -/- ) background for Pin1 were experimentally infected with RML prions. The study indicates that, neither the total depletion nor reduced levels of Pin1 significantly altered the clinical and neuropathological features of the disease.

  15. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alanine amino transferase (ALT/SGPT) test system... Test Systems § 862.1030 Alanine amino transferase (ALT/SGPT) test system. (a) Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended to measure the activity of the...

  16. Functional analysis and localisation of a delta-class glutathione S-transferase from Sarcoptes scabiei.

    Science.gov (United States)

    Pettersson, Eva U; Ljunggren, Erland L; Morrison, David A; Mattsson, Jens G

    2005-01-01

    The mite Sarcoptes scabiei causes sarcoptic mange, or scabies, a disease that affects both animals and humans worldwide. Our interest in S. scabiei led us to further characterise a glutathione S-transferase. This multifunctional enzyme is a target for vaccine and drug development in several parasitic diseases. The S. scabiei glutathione S-transferase open reading frame reported here is 684 nucleotides long and yields a protein with a predicted molecular mass of 26 kDa. Through phylogenetic analysis the enzyme was classified as a delta-class glutathione S-transferase, and our paper is the first to report that delta-class glutathione S-transferases occur in organisms other than insects. The recombinant S. scabiei glutathione S-transferase was expressed in Escherichia coli via three different constructs and purified for biochemical analysis. The S. scabiei glutathione S-transferase was active towards the substrate 1-chloro-2,4-dinitrobenzene, though the positioning of fusion partners influenced the kinetic activity of the enzyme. Polyclonal antibodies raised against S. scabiei glutathione S-transferase specifically localised the enzyme to the integument of the epidermis and cavities surrounding internal organs in adult parasites. However, some minor staining of parasite intestines was observed. No staining was seen in host tissues, nor could we detect any antibody response against S. scabiei glutathione S-transferase in sera from naturally S. scabiei infected dogs or pigs. Additionally, the polyclonal sera raised against recombinant S. scabiei glutathione S-transferase readily detected a protein from mites, corresponding to the predicted size of native glutathione S-transferase.

  17. Carnitine palmityl transferase I deficiency

    NARCIS (Netherlands)

    Al-Aqeel, A. I.; Rashed, M. S.; Ruiter, J. P.; Al-Husseini, H. F.; Al-Amoudi, M. S.; Wanders, R. J.

    2001-01-01

    Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected

  18. Serum glutathione transferase does not respond to indole-3-carbinol: A pilot study

    Directory of Open Access Journals (Sweden)

    Daniel R McGrath

    2010-05-01

    Full Text Available Daniel R McGrath1, Hamid Frydoonfar2, Joshua J Hunt3, Chris J Dunkley3, Allan D Spigelman41Ipswich Hospital, Ipswich, UK; 2Hunter Pathology Service, New South Wales; 3Royal Newcastle Centre, Newcastle; 4St Vincent’s Clinical School, Sydney, AustraliaBackground: Despite the well recognized protective effect of cruciferous vegetables against various cancers, including human colorectal cancers, little is known about how this effect is conferred. It is thought that some phytochemicals found only in these vegetables confer the protection. These compounds include the glucosinolates, of which indole-3-carbinol is one. They are known to induce carcinogen-metabolizing (phase II enzymes, including the glutathione S-transferase (GST family. Other effects in humans are not well documented. We wished to assess the effect of indole-3-carbinol on GST enzymes.Methods: We carried out a placebo-controlled human volunteer study. All patients were given 400 mg daily of indole-3-carbinol for three months, followed by placebo. Serum samples were tested for the GSTM1 genotype by polymerase chain reaction. Serum GST levels were assessed using enzyme-linked immunosorbent assay and Western Blot methodologies.Results: Forty-nine volunteers completed the study. GSTM1 genotypes were obtained for all but two volunteers. A slightly greater proportion of volunteers were GSTM1-positive, in keeping with the general population. GST was detected in all patients. Total GST level was not affected by indole-3-carbinol dosing compared with placebo. Although not statistically significant, the GSTM1 genotype affected the serum GST level response to indole-3-carbinol.Conclusion: Indole-3-carbinol does not alter total serum GST levels during prolonged dosing.Keywords: pilot study, colorectal cancer, glutathione transferase, human, indole-3-carbinol

  19. Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety

    Science.gov (United States)

    Shang, Ruofeng; Wang, Shengyu; Xu, Ximing; Yi, Yunpeng; Guo, Wenzhu; YuLiu; Liang, Jianping

    2013-01-01

    Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA. PMID:24376551

  20. Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety.

    Directory of Open Access Journals (Sweden)

    Ruofeng Shang

    Full Text Available Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC of 23S rRNA.

  1. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  2. The association between glutathione S-transferase P1 ...

    African Journals Online (AJOL)

    Mahmoud I. Mahmoud

    2011-08-10

    Aug 10, 2011 ... B-adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care ... transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997;18(4):641–4.

  3. Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma

    International Nuclear Information System (INIS)

    Hayes, J.D.; Gilligan, D.; Beckett, G.J.

    1983-01-01

    A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements. (Auth.)

  4. Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, J.D.; Gilligan, D.; Beckett, G.J. (Edinburgh Univ. (UK). Dept. of Clinical Chemistry); Chapman, B.J. (Royal Infirmary, Edinburgh (UK))

    1983-10-31

    A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements.

  5. Presence of a Ca2+-sensitive CDPdiglyceride-inositol transferase in canine cardiac sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Kasinathan, C.; Kirchberger, M.A.

    1988-01-01

    Sarcoplasmic reticulum (SR) and plasma membranes from canine left ventricle were used to evaluate the presence of the enzyme CDPdiglyceride-inositol transferase in these membranes. (K + ,-Ca 2+ )-ATPase activity, a marker for SR, was 79.2 +/- 5.0 (SE) and 11.2 +/- 2.0 μmol x mg -1 x h -1 in SR and plasma membrane preparations, respectively, and (Na + , K + )-ATPase activity, a marker for plasma membranes, was 5.6 +/- 1.2 and 99.2 +/- 8.0 μmol x mg -1 x h -1 , respectively. Contamination of SR and plasma membrane preparations by mitochondria was estimated to be 2% and 8%, respectively, and by Golgi membranes, 0.9% and 1.8%, respectively. The transferase activity detected in the plasma membrane preparation could be accounted for largely, but not entirely, by contaminating SR membranes. The pH optimum for the SR transferase activity was between 8.0 and 9.0. Ca 2+ inhibited the enzyme, half-maximal inhibition occurring at about 10 μM Ca 2+ . No loss of [ 3 H]PtdIns could be detected when membranes were incubated in the presence or absence of Ca 2+ . The Ca 2+ inhibition of the transferase was noncompetitive with respect to CDP-dipalmitin while that with respect to myo-inositol was slightly noncompetitive at low [Ca 2+ ] and became uncompetitive at higher [Ca 2+ ]. It is concluded that CDPdiglyceride-inositol transferase is present on SR membranes and is sensitive to micromolar Ca 2+ . The data are consistent with a putative role for the inhibition of the SR transferase by Ca 2+ and acidic pH in the protection of the SR against calcium overload in ischemic myocardium

  6. Insecticide resistance and glutathione S-transferases in mosquitoes ...

    African Journals Online (AJOL)

    Mosquito glutathione S-transferases (GSTs) have received considerable attention in the last 20 years because of their role in insecticide metabolism producing resistance. Many different compounds, including toxic xenobiotics and reactive products of intracellular processes such as lipid peroxidation, act as GST substrates.

  7. Ribosomal history reveals origins of modern protein synthesis.

    Directory of Open Access Journals (Sweden)

    Ajith Harish

    Full Text Available The origin and evolution of the ribosome is central to our understanding of the cellular world. Most hypotheses posit that the ribosome originated in the peptidyl transferase center of the large ribosomal subunit. However, these proposals do not link protein synthesis to RNA recognition and do not use a phylogenetic comparative framework to study ribosomal evolution. Here we infer evolution of the structural components of the ribosome. Phylogenetic methods widely used in morphometrics are applied directly to RNA structures of thousands of molecules and to a census of protein structures in hundreds of genomes. We find that components of the small subunit involved in ribosomal processivity evolved earlier than the catalytic peptidyl transferase center responsible for protein synthesis. Remarkably, subunit RNA and proteins coevolved, starting with interactions between the oldest proteins (S12 and S17 and the oldest substructure (the ribosomal ratchet in the small subunit and ending with the rise of a modern multi-subunit ribosome. Ancestral ribonucleoprotein components show similarities to in vitro evolved RNA replicase ribozymes and protein structures in extant replication machinery. Our study therefore provides important clues about the chicken-or-egg dilemma associated with the central dogma of molecular biology by showing that ribosomal history is driven by the gradual structural accretion of protein and RNA structures. Most importantly, results suggest that functionally important and conserved regions of the ribosome were recruited and could be relics of an ancient ribonucleoprotein world.

  8. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic

  9. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria

    DEFF Research Database (Denmark)

    Giessing, Anders; Jensen, Søren Skov; Rasmussen, Anette

    2009-01-01

    The Cfr methyltransferase confers combined resistance to five different classes of antibiotics that bind to the peptidyl transferase center of bacterial ribosomes. The Cfr-mediated modification has previously been shown to occur on nucleotide A2503 of 23S rRNA and has a mass corresponding......,8-dimethyladenosine. The mutation of single conserved cysteine residues in the radical SAM motif CxxxCxxC of Cfr abolishes its activity, lending support to the notion that the Cfr modification reaction occurs via a radical-based mechanism. Antibiotic susceptibility data confirm that the antibiotic resistance...

  10. Glutathione S - transferases class Pi and Mi and their significance in oncology

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2017-06-01

    Full Text Available In this article the current data, which shows that glutathione S-transferases (GST class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

  11. Glutathione S - transferases class Pi and Mi and their significance in oncology.

    Science.gov (United States)

    Marchewka, Zofia; Piwowar, Agnieszka; Ruzik, Sylwia; Długosz, Anna

    2017-06-19

    In this article the current data, which shows that glutathione S-transferases (GST) class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi) in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

  12. Characterization of Affinity-Purified Isoforms of Acinetobacter calcoaceticus Y1 Glutathione Transferases

    Directory of Open Access Journals (Sweden)

    Chin-Soon Chee

    2014-01-01

    Full Text Available Glutathione transferases (GST were purified from locally isolated bacteria, Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion exchange, and their substrate specificities were investigated. SDS-polyacrylamide gel electrophoresis revealed that the purified GST resolved into a single band with a molecular weight (MW of 23 kDa. 2-dimensional (2-D gel electrophoresis showed the presence of two isoforms, GST1 (pI 4.5 and GST2 (pI 6.2 with identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active towards all substrates except hydrogen peroxide. This demonstrated that GST1 possessed peroxidase activity which was absent in GST2. This study also showed that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase and F0KKB0 (glutathione S-transferase III of Acinetobacter calcoaceticus strain PHEA-2, respectively.

  13. Characterization of Affinity-Purified Isoforms of Acinetobacter calcoaceticus Y1 Glutathione Transferases

    Science.gov (United States)

    Chee, Chin-Soon; Tan, Irene Kit-Ping; Alias, Zazali

    2014-01-01

    Glutathione transferases (GST) were purified from locally isolated bacteria, Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion exchange, and their substrate specificities were investigated. SDS-polyacrylamide gel electrophoresis revealed that the purified GST resolved into a single band with a molecular weight (MW) of 23 kDa. 2-dimensional (2-D) gel electrophoresis showed the presence of two isoforms, GST1 (pI 4.5) and GST2 (pI 6.2) with identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active towards all substrates except hydrogen peroxide. This demonstrated that GST1 possessed peroxidase activity which was absent in GST2. This study also showed that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase) and F0KKB0 (glutathione S-transferase III) of Acinetobacter calcoaceticus strain PHEA-2, respectively. PMID:24892084

  14. A glutathione s-transferase confers herbicide tolerance in rice

    Directory of Open Access Journals (Sweden)

    Tingzhang Hu

    2014-07-01

    Full Text Available Plant glutathione S-transferases (GSTs have been a focus of attention due to their role in herbicide detoxification. OsGSTL2 is a glutathione S-transferase, lambda class gene from rice (Oryza sativa L.. Transgenic rice plants over-expressing OsGSTL2 were generated from rice calli by the use of an Agrobacterium transformation system, and were screened by a combination of hygromycin resistance, PCR and Southern blot analysis. In the vegetative tissues of transgenic rice plants, the over-expression of OsGSTL2 not only increased levels of OsGSTL2 transcripts, but also GST and GPX expression, while reduced superoxide. Transgenic rice plants also showed higher tolerance to glyphosate and chlorsulfuron, which often contaminate agricultural fields. The findings demonstrate the detoxification role of OsGSTL2 in the growth and development of rice plants. It should be possible to apply the present results to crops for developing herbicide tolerance and for limiting herbicide contamination in the food chain.

  15. Mapping of Complete Set of Ribose and Base Modifications of Yeast rRNA by RP-HPLC and Mung Bean Nuclease Assay.

    Directory of Open Access Journals (Sweden)

    Jun Yang

    Full Text Available Ribosomes are large ribonucleoprotein complexes that are fundamental for protein synthesis. Ribosomes are ribozymes because their catalytic functions such as peptidyl transferase and peptidyl-tRNA hydrolysis depend on the rRNA. rRNA is a heterogeneous biopolymer comprising of at least 112 chemically modified residues that are believed to expand its topological potential. In the present study, we established a comprehensive modification profile of Saccharomyces cerevisiae's 18S and 25S rRNA using a high resolution Reversed-Phase High Performance Liquid Chromatography (RP-HPLC. A combination of mung bean nuclease assay, rDNA point mutants and snoRNA deletions allowed us to systematically map all ribose and base modifications on both rRNAs to a single nucleotide resolution. We also calculated approximate molar levels for each modification using their UV (254nm molar response factors, showing sub-stoichiometric amount of modifications at certain residues. The chemical nature, their precise location and identification of partial modification will facilitate understanding the precise role of these chemical modifications, and provide further evidence for ribosome heterogeneity in eukaryotes.

  16. Steroid sulfatase and sulfuryl transferase activities in human brain tumors

    Czech Academy of Sciences Publication Activity Database

    Kříž, L.; Bičíková, M.; Mohapl, M.; Hill, M.; Černý, Ivan; Hampl, R.

    2008-01-01

    Roč. 109, č. 1 (2008), s. 31-39 ISSN 0960-0760 Institutional research plan: CEZ:AV0Z40550506 Keywords : dehydroepiandrosterone * steroid sulfatase * steroid sulfuryl transferase * brain Subject RIV: CC - Organic Chemistry Impact factor: 2.827, year: 2008

  17. Homogentisate solanesyl transferase (HST) cDNA’s in maize

    Science.gov (United States)

    Maize white seedling 3 (w3) has served as a model albino-seedling mutant since its discovery in 1923. We show that the w3 phenotype is caused by disruptions in homogentisate solanesyl transferase (HST), an enzyme that catalyzes the committed step in plastoquinone-9 (PQ9) biosynthesis. This reaction ...

  18. Iron enhances the peptidyl deformylase activity and biofilm formation in Staphylococcus aureus.

    Science.gov (United States)

    Swarupa, Vimjam; Chaudhury, Abhijit; Sarma, Potukuchi Venkata Gurunadha Krishna

    2018-01-01

    Staphylococcus aureus plays a major role in persistent infections and many of these species form structured biofilms on different surfaces which is accompanied by changes in gene expression profiles. Further, iron supplementation plays a critical role in the regulation of several protein(s)/enzyme function, which all aid in the development of active bacterial biofilms. It is well known that for each protein, deformylation is the most crucial step in biosynthesis and is catalyzed by peptidyl deformylase (PDF). Thus, the aim of the current study is to understand the role of iron in biofilm formation and deformylase activity of PDF. Hence, the PDF gene of S. aureus ATCC12600 was PCR amplified using specific primers and sequenced, followed by cloning and expression in Escherichia coli DH5α. The deformylase activity of the purified recombinant PDF was measured in culture supplemented with/without iron where the purified rPDF showed K m of 1.3 mM and V max of 0.035 mM/mg/min, which was close to the native PDF ( K m  = 1.4 mM, V max  = 0.030 mM/mg/min). Interestingly, the K m decreased and PDF activity increased when the culture was supplemented with iron, corroborating with qPCR results showing 100- to 150-fold more expression compared to control in S. aureus and its drug-resistant strains. Further biofilm-forming units (BU) showed an incredible increase (0.42 ± 0.005 to 6.3 ± 0.05 BU), i.e., almost 15-fold elevation in anaerobic conditions, indicating the significance of iron in S. aureus biofilms.

  19. Acrolein-detoxifying isozymes of glutathione transferase in plants.

    Science.gov (United States)

    Mano, Jun'ichi; Ishibashi, Asami; Muneuchi, Hitoshi; Morita, Chihiro; Sakai, Hiroki; Biswas, Md Sanaullah; Koeduka, Takao; Kitajima, Sakihito

    2017-02-01

    Acrolein is a lipid-derived highly reactive aldehyde, mediating oxidative signal and damage in plants. We found acrolein-scavenging glutathione transferase activity in plants and purified a low K M isozyme from spinach. Various environmental stressors on plants cause the generation of acrolein, a highly toxic aldehyde produced from lipid peroxides, via the promotion of the formation of reactive oxygen species, which oxidize membrane lipids. In mammals, acrolein is scavenged by glutathione transferase (GST; EC 2.5.1.18) isozymes of Alpha, Pi, and Mu classes, but plants lack these GST classes. We detected the acrolein-scavenging GST activity in four species of plants, and purified an isozyme showing this activity from spinach (Spinacia oleracea L.) leaves. The isozyme (GST-Acr), obtained after an affinity chromatography and two ion exchange chromatography steps, showed the K M value for acrolein 93 μM, the smallest value known for acrolein-detoxifying enzymes in plants. Peptide sequence homology search revealed that GST-Acr belongs to the GST Tau, a plant-specific class. The Arabidopsis thaliana GST Tau19, which has the closest sequence similar to spinach GST-Acr, also showed a high catalytic efficiency for acrolein. These results suggest that GST plays as a scavenger for acrolein in plants.

  20. Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase.

    Science.gov (United States)

    Pettersson, Par L; Johansson, Ann-Sofie; Mannervik, Bengt

    2002-08-16

    A major goal in protein engineering is the tailor-making of enzymes for specified chemical reactions. Successful attempts have frequently been based on directed molecular evolution involving libraries of random mutants in which variants with desired properties were identified. For the engineering of enzymes with novel functions, it would be of great value if the necessary changes of the active site could be predicted and implemented. Such attempts based on the comparison of similar structures with different substrate selectivities have previously met with limited success. However, the present work shows that the knowledge-based redesign restricted to substrate-binding residues in human glutathione transferase A2-2 can introduce high steroid double-bond isomerase activity into the enzyme originally characterized by glutathione peroxidase activity. Both the catalytic center activity (k(cat)) and catalytic efficiency (k(cat)/K(m)) match the values of the naturally evolved glutathione transferase A3-3, the most active steroid isomerase known in human tissues. The substrate selectivity of the mutated glutathione transferase was changed 7000-fold by five point mutations. This example demonstrates the functional plasticity of the glutathione transferase scaffold as well as the potential of rational active-site directed mutagenesis as a complement to DNA shuffling and other stochastic methods for the redesign of proteins with novel functions.

  1. Cooperation of terminal deoxynucleotidyl transferase with DNA polymerase α in the replication of ultraviolet-irradiated DNA

    International Nuclear Information System (INIS)

    Yoshida, S.; Masaki, S.; Nakamura, H.; Morita, T.

    1981-01-01

    The amount of DNA synthesis in vitro with the ultraviolet-irradiated poly(dT).oligo(rA) template initiators catalysed by DNA polymerase α (Masaki, S. and Yoshida, S., Biochim. Biophys. Acta 521, 74-88) decreased with the dose of ultraviolet-irradiation. The ultraviolet irradiation to the template, however, did not affect the rate of incorporation of incorrect deoxynucleotides into the newly synthesized poly(dA). The addition of terminal deoxynucleotidyl transferase to this system enhanced the DNA synthesis to a level which is comparable to that of the control and it concomitantly increased the incorporation of the mismatched deoxynucleotide into the newly synthesized poly(dA) strands. On the other hand, with an unirradiated template initiator, the misincorporation was only slightly enhanced by the addition of terminal deoxynucleotidyl transferase. The sizes of newly synthesized DNA measured by the sedimentation velocities were found to be smaller with the ultraviolet-irradiated templates but they increased to the control level with the addition of terminal deoxynucleotidyl transferase to the systems. These results suggest that terminal deoxynucleotidyl transferase can help DNA polymerase α to bypass thymine dimers in vitro by the formation of mismatched regions at the positions opposite to pyrimidine dimers on the template. (Auth.)

  2. THE MECHANISM OF PROTEIN BIOSYNTHESIS*

    African Journals Online (AJOL)

    1971-04-17

    Apr 17, 1971 ... RNA. A fragment of 74 nucleotides long has been deter- mined. Although this sequence contains three potential initiation codons (two AUG and one .... Studies with antibiotics, presented by Vazquez et al.,' suggest that there is only one peptidyl synthetase centre on each 50S subunit. After formation of the ...

  3. Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Bennett, Eric P; Schjoldager, Katrine T-B G

    2011-01-01

    UDP-GalNAc:polypeptide a-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection...... of glycosylation sites by GalNAc-Ts: confined sequence recognition by the catalytic domain alone, and concerted recognition of acceptor sites and adjacent GalNAc-glycosylated sites by the catalytic and lectin domains, respectively. Thus far, only the catalytic domain has been shown to have peptide sequence...... on sequences of mucins MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC7 as well as a random glycopeptide bead library, we examined the binding properties of four different lectin domains. The lectin domains of GalNAc-T1, -T2, -T3, and -T4 bound different subsets of small glycopeptides. These results indicate...

  4. Development of isoform-specific sensors of polypeptide GalNAc-transferase activity

    DEFF Research Database (Denmark)

    Song, Lina; Bachert, Collin; Schjoldager, Katrine T

    2014-01-01

    sequence influenced their activity and required modification, which we carried out based on previous in vitro work. Significantly, the modified T2 and T3 sensors were activated only in cells lacking their corresponding isozymes. Thus, we have developed T2- and T3-specific sensors that will be valuable......Humans express up to 20 isoforms of GalNAc-transferase (herein T1-T20) that localize to the Golgi apparatus and initiate O-glycosylation. Regulation of this enzyme family affects a vast array of proteins transiting the secretory pathway and diseases arise upon misregulation of specific isoforms....... Surprisingly, molecular probes to monitor GalNAc-transferase activity are lacking and there exist no effective global or isoform-specific inhibitors. Here we describe the development of T2- and T3-isoform specific fluorescence sensors that traffic in the secretory pathway. Each sensor yielded little signal...

  5. Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.

    Directory of Open Access Journals (Sweden)

    Hyeong-Jun Han

    Full Text Available Peptidyl prolyl isomerase (PIN1 regulates the functional activity of a subset of phosphoproteins through binding to phosphorylated Ser/Thr-Pro motifs and subsequently isomerization of the phosphorylated bonds. Interestingly, PIN1 is overexpressed in many types of malignancies including breast, prostate, lung and colon cancers. However, its oncogenic functions have not been fully elucidated. Here, we report that PIN1 directly interacts with hypoxia-inducible factor (HIF-1α in human colon cancer (HCT116 cells. PIN1 binding to HIF-1α occurred in a phosphorylation-dependent manner. We also found that PIN1 interacted with HIF-1α at both exogenous and endogenous levels. Notably, PIN1 binding stabilized the HIF-1α protein, given that their levels were significantly increased under hypoxic conditions. The stabilization of HIF-1α resulted in increased transcriptional activity, consequently upregulating expression of vascular endothelial growth factor, a major contributor to angiogenesis. Silencing of PIN1 or pharmacologic inhibition of its activity abrogated the angiogenesis. By utilizing a bioluminescence imaging technique, we were able to demonstrate that PIN1 inhibition dramatically reduced the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of HIF-1α. These results suggest that PIN1 interacting with HIF-1α is a potential cancer chemopreventive and therapeutic target.

  6. Peptidyl prolyl isomerase Pin1-inhibitory activity of D-glutamic and D-aspartic acid derivatives bearing a cyclic aliphatic amine moiety.

    Science.gov (United States)

    Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki

    2015-12-01

    Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast

    DEFF Research Database (Denmark)

    Kampranis, S C; Damianova, R; Atallah, M

    2000-01-01

    The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allows...... for the identification of plant genes, which inhibit either directly or indirectly the lethal phenotype of Bax. Using this method a number of cDNA clones were isolated, the more potent of which encodes a protein homologous to the class theta glutathione S-transferases. This Bax-inhibiting (BI) protein was expressed...... in Escherichia coli and found to possess glutathione S-transferase (GST) and weak glutathione peroxidase (GPX) activity. Expression of Bax in yeast decreases the intracellular levels of total glutathione, causes a substantial reduction of total cellular phospholipids, diminishes the mitochondrial membrane...

  8. A 4'-phosphopantetheinyl transferase mediates non-ribosomal peptide synthetase activation in Aspergillus fumigatus.

    Science.gov (United States)

    Neville, Claire; Murphy, Alan; Kavanagh, Kevin; Doyle, Sean

    2005-04-01

    Aspergillus fumigatus is a significant human pathogen. Non-ribosomal peptide (NRP) synthesis is thought to be responsible for a significant proportion of toxin and siderophore production in the organism. Furthermore, it has been shown that 4'-phosphopantetheinylation is required for the activation of key enzymes involved in non-ribosomal peptide synthesis in other species. Here we report the cloning, recombinant expression and functional characterisation of a 4'-phosphopantetheinyl transferase from A. fumigatus and the identification of an atypical NRP synthetase (Afpes1), spanning 14.3 kb. Phylogenetic analysis has shown that the NRP synthetase exhibits greatest identity to NRP synthetases from Metarhizium anisolpiae (PesA) and Alternaria brassicae (AbrePsy1). Northern hybridisation and RT-PCR analysis have confirmed that both genes are expressed in A. fumigatus. A 120 kDa fragment of the A. fumigatus NRP synthetase, containing a putative thiolation domain, was cloned and expressed in the baculovirus expression system. Detection of a 4'-phosphopantetheinylated peptide (SFSAMK) from this protein, by MALDI-TOF mass spectrometric analysis after coincubation of the 4'-phosphopantetheinyl transferase with the recombinant NRP synthetase fragment and acetyl CoA, confirms that it is competent to play a role in NRP synthetase activation in A. fumigatus. The 4'-phosphopantetheinyl transferase also activates, by 4'-phosphopantetheinylation, recombinant alpha-aminoadipate reductase (Lys2p) from Candida albicans, a key enzyme involved in lysine biosynthesis.

  9. Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

    International Nuclear Information System (INIS)

    Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas; Goulding, Celia W.

    2014-01-01

    The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully

  10. Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas [UC Irvine, 2212 Natural Sciences I, Irvine, CA 92697 (United States); Goulding, Celia W., E-mail: celia.goulding@uci.edu [UC Irvine, 2212 Natural Sciences I, Irvine, CA 92697 (United States); UC Irvine, 2302 Natural Sciences I, Irvine, CA 92697 (United States)

    2014-04-01

    The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully

  11. Receptor type I and type II binding regions and the peptidyl-prolyl isomerase site of cyclophilin B are required for enhancement of T-lymphocyte adhesion to fibronectin.

    Science.gov (United States)

    Carpentier, Mathieu; Allain, Fabrice; Slomianny, Marie-Christine; Durieux, Sandrine; Vanpouille, Christophe; Haendler, Bernard; Spik, Geneviève

    2002-04-23

    Cyclophilin B (CyPB), a cyclosporin A (CsA) binding protein, interacts with two types of binding sites at the surface of T-lymphocytes. The type I sites correspond to functional receptors involved in endocytosis and the type II sites to sulfated glycosaminoglycans (GAGs). Mutational analysis of CyPB has revealed that W128, which is part of the CsA-binding pocket, is implicated in the binding to the functional type I receptors and that two amino acid clusters located in the N-terminus ensure the binding to GAGs. The peptidyl-prolyl isomerase activity of CyPB is not required for receptor binding. We have recently demonstrated that CyPB enhances adhesion of peripheral blood T-lymphocytes to fibronectin, a component of the extracellular matrix. We intended to identify additional amino acids involved in the binding of CyPB to its functional type I receptor and to determine regions responsible for the stimulation of peripheral blood T-lymphocyte adhesion. We determined that residues R76, G77, K132, D155, and D158 of the calcineurin (CN) interacting region were implicated in the recognition of type I receptor but not of GAGs. We also found that two different changes in the N-terminal extension that abated binding to GAGs prevented adhesion of peripheral blood T-lymphocytes to coated CyPB, whereas abbrogation of the PPIase activity had no effect. On the other hand, the adhesion of peripheral blood T-lymphocytes to coated fibronectin was not stimulated by CyPB mutants devoid of either type I receptor or GAGs binding activity or by mutants of the PPIase site. Altogether, the results demonstrate that different regions of CyPB are involved in peripheral blood T-lymphocyte activation and imply a novel important physiological function for peptidyl-prolyl isomerase activity.

  12. Genomic organization of plant aminopropyl transferases.

    Science.gov (United States)

    Rodríguez-Kessler, Margarita; Delgado-Sánchez, Pablo; Rodríguez-Kessler, Gabriela Theresia; Moriguchi, Takaya; Jiménez-Bremont, Juan Francisco

    2010-07-01

    Aminopropyl transferases like spermidine synthase (SPDS; EC 2.5.1.16), spermine synthase and thermospermine synthase (SPMS, tSPMS; EC 2.5.1.22) belong to a class of widely distributed enzymes that use decarboxylated S-adenosylmethionine as an aminopropyl donor and putrescine or spermidine as an amino acceptor to form in that order spermidine, spermine or thermospermine. We describe the analysis of plant genomic sequences encoding SPDS, SPMS, tSPMS and PMT (putrescine N-methyltransferase; EC 2.1.1.53). Genome organization (including exon size, gain and loss, as well as intron number, size, loss, retention, placement and phase, and the presence of transposons) of plant aminopropyl transferase genes were compared between the genomic sequences of SPDS, SPMS and tSPMS from Zea mays, Oryza sativa, Malus x domestica, Populus trichocarpa, Arabidopsis thaliana and Physcomitrella patens. In addition, the genomic organization of plant PMT genes, proposed to be derived from SPDS during the evolution of alkaloid metabolism, is illustrated. Herein, a particular conservation and arrangement of exon and intron sequences between plant SPDS, SPMS and PMT genes that clearly differs with that of ACL5 genes, is shown. The possible acquisition of the plant SPMS exon II and, in particular exon XI in the monocot SPMS genes, is a remarkable feature that allows their differentiation from SPDS genes. In accordance with our in silico analysis, functional complementation experiments of the maize ZmSPMS1 enzyme (previously considered to be SPDS) in yeast demonstrated its spermine synthase activity. Another significant aspect is the conservation of intron sequences among SPDS and PMT paralogs. In addition the existence of microsynteny among some SPDS paralogs, especially in P. trichocarpa and A. thaliana, supports duplication events of plant SPDS genes. Based in our analysis, we hypothesize that SPMS genes appeared with the divergence of vascular plants by a processes of gene duplication and the

  13. Structures of a putative ζ-class glutathione S-transferase from the pathogenic fungus Coccidioides immitis

    International Nuclear Information System (INIS)

    Edwards, Thomas E.; Bryan, Cassie M.; Leibly, David J.; Dieterich, Shellie H.; Abendroth, Jan; Sankaran, Banumathi; Sivam, Dhileep; Staker, Bart L.; Van Voorhis, Wesley C.; Myler, Peter J.; Stewart, Lance J.

    2011-01-01

    The pathogenic fungus C. immitis causes coccidioidomycosis, a potentially fatal disease. Here, apo and glutathione-bound crystal structures of a previously uncharacterized protein from C. immitis that appears to be a ζ-class glutathione S-transferase are presented. Coccidioides immitis is a pathogenic fungus populating the southwestern United States and is a causative agent of coccidioidomycosis, sometimes referred to as Valley Fever. Although the genome of this fungus has been sequenced, many operons are not properly annotated. Crystal structures are presented for a putative uncharacterized protein that shares sequence similarity with ζ-class glutathione S-transferases (GSTs) in both apo and glutathione-bound forms. The apo structure reveals a nonsymmetric homodimer with each protomer comprising two subdomains: a C-terminal helical domain and an N-terminal thioredoxin-like domain that is common to all GSTs. Half-site binding is observed in the glutathione-bound form. Considerable movement of some components of the active site relative to the glutathione-free form was observed, indicating an induced-fit mechanism for cofactor binding. The sequence homology, structure and half-site occupancy imply that the protein is a ζ-class glutathione S-transferase, a maleylacetoacetate isomerase (MAAI)

  14. Characterization of glutathione transferases involved in the pathogenicity of Alternaria brassicicola.

    Science.gov (United States)

    Calmes, Benoit; Morel-Rouhier, Mélanie; Bataillé-Simoneau, Nelly; Gelhaye, Eric; Guillemette, Thomas; Simoneau, Philippe

    2015-06-18

    Glutathione transferases (GSTs) represent an extended family of multifunctional proteins involved in detoxification processes and tolerance to oxidative stress. We thus anticipated that some GSTs could play an essential role in the protection of fungal necrotrophs against plant-derived toxic metabolites and reactive oxygen species that accumulate at the host-pathogen interface during infection. Mining the genome of the necrotrophic Brassica pathogen Alternaria brassicicola for glutathione transferase revealed 23 sequences, 17 of which could be clustered into the main classes previously defined for fungal GSTs and six were 'orphans'. Five isothiocyanate-inducible GSTs from five different classes were more thoroughly investigated. Analysis of their catalytic properties revealed that two GSTs, belonging to the GSTFuA and GTT1 classes, exhibited GSH transferase activity with isothiocyanates (ITC) and peroxidase activity with cumene hydroperoxide, respectively. Mutant deficient for these two GSTs were however neither more susceptible to ITC nor less aggressive than the wild-type parental strain. By contrast mutants deficient for two other GSTs, belonging to the Ure2pB and GSTO classes, were distinguished by their hyper-susceptibility to ITC and low aggressiveness against Brassica oleracea. In particular AbGSTO1 could participate in cell tolerance to ITC due to its glutathione-dependent thioltransferase activity. The fifth ITC-inducible GST belonged to the MAPEG class and although it was not possible to produce the soluble active form of this protein in a bacterial expression system, the corresponding deficient mutant failed to develop normal symptoms on host plant tissues. Among the five ITC-inducible GSTs analyzed in this study, three were found essential for full aggressiveness of A. brassicicola on host plant. This, to our knowledge is the first evidence that GSTs might be essential virulence factors for fungal necrotrophs.

  15. Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

    OpenAIRE

    Matsumoto, M; Imagawa, M; Aoki, Y

    2000-01-01

    Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did no...

  16. Global deletion of glutathione S-Transferase A4 exacerbates developmental nonalcoholic steatohepatitis

    Science.gov (United States)

    We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 (Gsta4-/-)/peroxisome proliferator activated receptor a (Ppara-/-) double knockout 129/SvJ mice for 12 weeks from weaning. We us...

  17. Resistance to linezolid in Staphylococcus spp. clinical isolates associated with ribosomal binding site modifications: novel mutation in domain V of 23S rRNA.

    Science.gov (United States)

    Musumeci, Rosario; Calaresu, Enrico; Gerosa, Jolanda; Oggioni, Davide; Bramati, Simone; Morelli, Patrizia; Mura, Ida; Piana, Andrea; Are, Bianca Maria; Cocuzza, Clementina Elvezia

    2016-10-01

    Linezolid is the main representative of the oxazolidinones, introduced in 2000 in clinical practice to treat severe Gram-positive infections. This compound inhibits protein synthesis by binding to the peptidyl transferase centre of the 50S bacterial ribosomal subunit. The aim of this study was to characterize 12 clinical strains of linezolid-resistant Staphylococcus spp. isolated in Northern Italy. All isolates of Staphylococcus spp. studied showed a multi-antibiotic resistance phenotype. In particular, all isolates showed the presence of the mecA gene associated with SSCmec types IVa, V or I. Mutations in domain V of 23S rRNA were shown to be the most prevalent mechanism of linezolid resistance: among these a new C2551T mutation was found in S. aureus, whilst the G2576T mutation was shown to be the most prevalent overall. Moreover, three S. epidermidis isolates were shown to have linezolid resistance associated only with alterations in both L3 and L4 ribosomal proteins. No strain was shown to harbor the previously described cfr gene. These results have shown how the clinical use of linezolid in Northern Italy has resulted in the selection of multiple antibiotic-resistant clinical isolates of Staphylococcus spp., with linezolid resistance in these strains being associated with mutations in 23S rRNA or ribosomal proteins L3 and L4.

  18. Interaction of tRNA with Eukaryotic Ribosome

    Directory of Open Access Journals (Sweden)

    Dmitri Graifer

    2015-03-01

    Full Text Available This paper is a review of currently available data concerning interactions of tRNAs with the eukaryotic ribosome at various stages of translation. These data include the results obtained by means of cryo-electron microscopy and X-ray crystallography applied to various model ribosomal complexes, site-directed cross-linking with the use of tRNA derivatives bearing chemically or photochemically reactive groups in the CCA-terminal fragment and chemical probing of 28S rRNA in the region of the peptidyl transferase center. Similarities and differences in the interactions of tRNAs with prokaryotic and eukaryotic ribosomes are discussed with concomitant consideration of the extent of resemblance between molecular mechanisms of translation in eukaryotes and bacteria.

  19. Association study on glutathione S-transferase omega 1 and 2 and familial ALS

    NARCIS (Netherlands)

    van de Giessen, Elsmarieke; Fogh, Isabella; Gopinath, Sumana; Smith, Bradley; Hu, Xun; Powell, John; Andersen, Peter; Nicholson, Garth; Al Chalabi, Ammar; Shaw, Christopher E.

    2008-01-01

    Glutathione S-transferase omega 1 and 2 (GSTO1 and 2) protect from oxidative stress, a possible pathogenic mechanism underlying the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Significant association of age of onset in Alzheimer's

  20. Functional characterization of glutathione S-transferases associated with insecticide resistance in Tetranychus urticae

    NARCIS (Netherlands)

    Pavlidi, N.; Tseliou, V.; Riga, M.; Nauen, R.; Van Leeuwen, T.; Labrou, N.E.; Vontas, J.

    2015-01-01

    The two-spotted spider mite Tetranychus urticae is one of the most important agricultural pests world-wide. It is extremely polyphagous and develops resistance to acaricides. The overexpression of several glutathione S-transferases (GSTs) has been associated with insecticide resistance. Here, we

  1. Photoaffinity labelling of the active site of the rat glutathione transferases 3-3 and 1-1 and human glutathione transferase A1-1.

    OpenAIRE

    Cooke, R J; Björnestedt, R; Douglas, K T; McKie, J H; King, M D; Coles, B; Ketterer, B; Mannervik, B

    1994-01-01

    The glutathione transferases (GSTs) form a group of enzymes responsible for a wide range of molecular detoxications. The photoaffinity label S-(2-nitro-4-azidophenyl)glutathione was used to study the hydrophobic region of the active site of the rat liver GST 1-1 and 2-2 isoenzymes (class Alpha) as well as the rat class-Mu GST 3-3. Photoaffinity labelling was carried out using a version of S-(2-nitro-4-azidophenyl)glutathione tritiated in the arylazido ring. The labelling occurred with higher ...

  2. Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer, in Danish postmenopausal women

    DEFF Research Database (Denmark)

    Egeberg, Rikke; Olsen, Anja; Autrup, Herman

    2008-01-01

    The aim of this study was to investigate whether polymorphisms in N-acetyl transferase 1 and 2 modify the association between meat consumption and risk of breast cancer. A nested case-control study was conducted among 24697 postmenopausal women included in the 'Diet, Cancer and Health' cohort study...... (1993-2000). Three hundred and seventy-eight breast cancer cases were identified and matched to 378 controls. The incidence rate ratio (95% confidence interval) for breast cancer was 1.09 (1.02-1.17) for total meat, 1.15 (1.01-1.31) for red meat and 1.23 (1.04-1.45) for processed meat per 25 g daily...... total meat intake and red meat intake and breast cancer risk were confined to intermediate/fast N-acetyl transferase 2 acetylators (P-interaction=0.03 and 0.04). Our findings support an association between meat consumption and breast cancer risk and that N-acetyl transferase 2 polymorphism has...

  3. Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting

    Directory of Open Access Journals (Sweden)

    Ozge Korkmaz

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located, and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9; second group (thrombus in main pulmonary artery branches; n = 71; third group (thrombus in pulmonary artery segmental branches; n = 34; and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8. RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009 and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033 remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

  4. Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe.

    Science.gov (United States)

    Mehta, Pramod Kumar; Lee, Hyeri; Lee, Keun-Hyeung

    2017-05-15

    The selective and sensitive detection of heparin, an anticoagulant in clinics as well as its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance. We first reported a ratiometric sensing method for heparin as well as OSCS contaminants in heparin using a fluorescent peptidyl probe (Pep1, pyrene-GSRKR) and heparin-digestive enzyme. Pep1 exhibited a highly sensitive ratiometric response to nanomolar concentration of heparin in aqueous solution over a wide pH range (2~11) and showed highly selective ratiometric response to heparin among biological competitors such as hyaluronic acid and chondroitin sulfate. Pep1 showed a linear ratiometric response to nanomolar concentrations of heparin in aqueous solutions and in human serum samples. The detection limit for heparin was calculated to be 2.46nM (R 2 =0.99) in aqueous solutions, 2.98nM (R 2 =0.98) in 1% serum samples, and 3.43nM (R 2 =0.99) in 5% serum samples. Pep1 was applied to detect the contaminated OSCS in heparin with heparinase I, II, and III, respectively. The ratiometric sensing method using Pep1 and heparinase II was highly sensitive, fast, and efficient for the detection of OSCS contaminant in heparin. Pep1 with heparinase II could detect as low as 0.0001% (w/w) of OSCS in heparin by a ratiometric response. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A novel method for screening the glutathione transferase inhibitors

    Directory of Open Access Journals (Sweden)

    Węgrzyn Grzegorz

    2009-03-01

    Full Text Available Abstract Background Glutathione transferases (GSTs belong to the family of Phase II detoxification enzymes. GSTs catalyze the conjugation of glutathione to different endogenous and exogenous electrophilic compounds. Over-expression of GSTs was demonstrated in a number of different human cancer cells. It has been found that the resistance to many anticancer chemotherapeutics is directly correlated with the over-expression of GSTs. Therefore, it appears to be important to find new GST inhibitors to prevent the resistance of cells to anticancer drugs. In order to search for glutathione transferase (GST inhibitors, a novel method was designed. Results Our results showed that two fragments of GST, named F1 peptide (GYWKIKGLV and F2 peptide (KWRNKKFELGLEFPNL, can significantly inhibit the GST activity. When these two fragments were compared with several known potent GST inhibitors, the order of inhibition efficiency (measured in reactions with 2,4-dinitrochlorobenzene (CDNB and glutathione as substrates was determined as follows: tannic acid > cibacron blue > F2 peptide > hematin > F1 peptide > ethacrynic acid. Moreover, the F1 peptide appeared to be a noncompetitive inhibitor of the GST-catalyzed reaction, while the F2 peptide was determined as a competitive inhibitor of this reaction. Conclusion It appears that the F2 peptide can be used as a new potent specific GST inhibitor. It is proposed that the novel method, described in this report, might be useful for screening the inhibitors of not only GST but also other enzymes.

  6. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: Identification and characterization

    NARCIS (Netherlands)

    K.W.A. Grinsven; S. Rosnowsky (Silke); S.W.H. van Weelden (Susanne); S. Pütz (Simone); M. van der Giezen (Mark); W. Martin (William); J.J. van Hellemond (Jaap); A.G.M. Tielens (Aloysius); K. Henze (Katrin)

    2008-01-01

    textabstractAcetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial

  7. Glutathione s-transferase isoenzymes in relation to their role in detoxification of xenobiotics

    NARCIS (Netherlands)

    Vos, R.M.E.

    1989-01-01

    The glutathione S-transferases (GST) are a family of isoenzymes serving a major part in the biotransformation of many reactive compounds. The isoenzymes from rat, man and mouse are divided into three classes, alpha, mu and pi, on the basis of similar structural and enzymatic

  8. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

  9. Expression of an enzymatically active Yb3 glutathione S-transferase in Escherichia coli and identification of its natural form in rat brain.

    Science.gov (United States)

    Abramovitz, M; Ishigaki, S; Felix, A M; Listowsky, I

    1988-11-25

    Glutathione S-transferases containing Yb3 subunits are relatively uncommon forms that are expressed in a tissue-specific manner and have not been identified unequivocally or characterized. A cDNA clone containing the entire coding sequence of Yb3 glutathione S-transferase mRNA was incorporated into a pIN-III expression vector used to transform Escherichia coli. A fusion Yb3-protein containing 14 additional amino acid residues at its N terminus was purified to homogeneity. Recombinant Yb3 was enzymatically active with both 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates but lacked glutathione peroxidase activity. Substrate specificity patterns of recombinant Yb3 were more limited than those of glutathione S-transferase isoenzymes containing Yb1- or Yb2-type subunits. Peptides corresponding to unique amino acid sequences of Yb3 as well as a peptide from a region of homology with Yb1 and Yb2 subunits were synthesized. These synthetic peptides were used to raise antibodies specific to Yb3 and others that cross-reacted with all Yb forms. Immunoblotting was utilized to identify the natural counterpart of recombinant Yb3 among rat glutathione transferases. Brain and testis glutathione S-transferases were rich in Yb3 subunits, but very little was found in liver or kidney. Physical properties, substrate specificities, and binding patterns of the recombinant protein paralleled properties of the natural isoenzyme isolated from brain.

  10. The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization

    DEFF Research Database (Denmark)

    Ross-Hansen, K; Linneberg, A; Johansen, J D

    2013-01-01

    BACKGROUND: Contact sensitization is frequent in the general population and arises from excessive or repeated skin exposure to chemicals and metals. However, little is known about its genetic susceptibility. OBJECTIVES: To determine the role of polymorphisms of glutathione S-transferase (GST) genes...

  11. Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine

    DEFF Research Database (Denmark)

    Pedersen, Lisbeth Nørum; Kaerlev, L; Stubbe Teglbjaerg, P

    2003-01-01

    Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We in...

  12. U2504 Determines the Species Specificity of the A-site Cleft Antibiotics: The sStructures of Tiamulin, Homoharringtonine and Bruceantin Bound to the Ribosome

    Energy Technology Data Exchange (ETDEWEB)

    Gurel, G.; Blaha, G; Moore, P; Steitz,

    2009-01-01

    Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 {angstrom}. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the A-site cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.

  13. U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome.

    Science.gov (United States)

    Gürel, Güliz; Blaha, Gregor; Moore, Peter B; Steitz, Thomas A

    2009-05-29

    Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 A. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the A-site cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.

  14. U2504 Determines the Species Specificity of the A-Site Cleft Antibiotics: The Structures of Tiamulin, Homoharringtonine, and Bruceantin Bound to the Ribosome

    Energy Technology Data Exchange (ETDEWEB)

    Gürel, Güliz; Blaha, Gregor; Moore, Peter B.; Steitz, Thomas A.; Yale

    2009-06-30

    Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 {angstrom}. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the Asite cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.

  15. Catalysis of Silver catfish Major Hepatic Glutathione Transferase proceeds via rapid equilibrium sequential random Mechanism

    Directory of Open Access Journals (Sweden)

    Ayodele O. Kolawole

    Full Text Available Fish hepatic glutathione transferases are connected with the elimination of intracellular pollutants and detoxification of organic micro-pollutants in their aquatic ecosystem. The two-substrate steady state kinetic mechanism of Silver catfish (Synodontis eupterus major hepatic glutathione transferases purified to apparent homogeneity was explored. The enzyme was dimeric enzyme with a monomeric size of 25.6 kDa. Initial-velocity studies and Product inhibition patterns by methyl glutathione and chloride with respect to GSH-CDNB; GSH-ρ-nitrophenylacetate; and GSH-Ethacrynic acid all conforms to a rapid equilibrium sequential random Bi Bi kinetic mechanism rather than steady state sequential random Bi Bi kinetic. α was 2.96 ± 0.35 for the model. The pH profile of Vmax/KM (with saturating 1-chloro-2,4-dinitrobenzene and variable GSH concentrations showed apparent pKa value of 6.88 and 9.86. Inhibition studies as a function of inhibitor concentration show that the enzyme is a homodimer and near neutral GST. The enzyme poorly conjugates 4-hydroxylnonenal and cumene hydroperoxide and may not be involved in oxidative stress protection. The seGST is unique and overwhelmingly shows characteristics similar to those of homodimeric class Pi GSTs, as was indicated by its kinetic mechanism, substrate specificity and inhibition studies. The rate- limiting step, probably the product release, of the reaction is viscosity-dependent and is consequential if macro-viscosogen or micro-viscosogen. Keywords: Silver catfish, Glutathione transferase, Steady-state, Kinetic mechanism, Inhibition

  16. β(1,3-glucanosyl-transferase activity is essential for cell wall integrity and viability of Schizosaccharomyces pombe.

    Directory of Open Access Journals (Sweden)

    María de Medina-Redondo

    Full Text Available BACKGROUND: The formation of the cell wall in Schizosaccharomyces pombe requires the coordinated activity of enzymes involved in the biosynthesis and modification of β-glucans. The β(1,3-glucan synthase complex synthesizes linear β(1,3-glucans, which remain unorganized until they are cross-linked to other β(1,3-glucans and other cell wall components. Transferases of the GH72 family play important roles in cell wall assembly and its rearrangement in Saccharomyces cerevisiae and Aspergillus fumigatus. Four genes encoding β(1,3-glucanosyl-transferases -gas1(+, gas2(+, gas4(+ and gas5(+- are present in S. pombe, although their function has not been analyzed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the characterization of the catalytic activity of gas1p, gas2p and gas5p together with studies directed to understand their function during vegetative growth. From the functional point of view, gas1p is essential for cell integrity and viability during vegetative growth, since gas1Δ mutants can only grow in osmotically supported media, while gas2p and gas5p play a minor role in cell wall construction. From the biochemical point of view, all of them display β(1,3-glucanosyl-transferase activity, although they differ in their specificity for substrate length, cleavage point and product size. In light of all the above, together with the differences in expression profiles during the life cycle, the S. pombe GH72 proteins may accomplish complementary, non-overlapping functions in fission yeast. CONCLUSIONS/SIGNIFICANCE: We conclude that β(1,3-glucanosyl-transferase activity is essential for viability in fission yeast, being required to maintain cell integrity during vegetative growth.

  17. Bisubstrate Kinetics of Glutathione S-Transferase: A Colorimetric Experiment for the Introductory Biochemistry Laboratory

    Science.gov (United States)

    Stefanidis, Lazaros; Scinto, Krystal V.; Strada, Monica I.; Alper, Benjamin J.

    2018-01-01

    Most biochemical transformations involve more than one substrate. Bisubstrate enzymes catalyze multiple chemical reactions in living systems and include members of the transferase, oxidoreductase, and ligase enzyme classes. Working knowledge of bisubstrate enzyme kinetic models is thus of clear importance to the practicing biochemist. However,…

  18. The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

    DEFF Research Database (Denmark)

    Beld, Joris; Sonnenschein, Eva; Vickery, Christopher R.

    2013-01-01

    Covering: up to 2013 Although holo-acyl carrier protein synthase, AcpS, a phosphopantetheinyl transferase (PPTase), was characterized in the 1960s, it was not until the publication of the landmark paper by Lambalot et al. in 1996 that PPTases garnered wide-spread attention being classified...... knowledge on this class of enzymes that post-translationally install a 4′-phosphopantetheine arm on various carrier proteins....

  19. Interactions of photoactive DNAs with terminal deoxynucleotidyl transferase: Identification of peptides in the DNA binding domain

    International Nuclear Information System (INIS)

    Farrar, Y.J.K.; Evans, R.K.; Beach, C.M.; Coleman, M.S.

    1991-01-01

    Terminal deoxynucleotidyl transferase (terminal transferase) was specifically modified in the DNA binding site by a photoactive DNA substrate (hetero-40-mer duplex containing eight 5-azido-dUMP residues at one 3' end). Under optimal photolabeling conditions, 27-40% of the DNA was covalently cross-linked to terminal transferase. The specificity of the DNA and protein interaction was demonstrated by protection of photolabeling at the DNA binding domain with natural DNA substrates. In order to recover high yields of modified peptides from limited amounts of starting material, protein modified with 32 P-labeled photoactive DNA and digested with trypsin was extracted 4 times with phenol followed by gel filtration chromatography. All peptides not cross-linked to DNA were extracted into the phenol phase while the photolyzed DNA and the covalently cross-linked peptides remained in the aqueous phase. The 32 P-containing peptide-DNA fraction was subjected to amino acid sequence analysis. Two sequences, Asp 221 -Lys 231 (peptide B8) and Cys 234 -Lys 249 (peptide B10), present in similar yield, were identified. Structure predictions placed the two peptides in an α-helical array of 39 angstrom which would accommodate a DNA helix span of 11 nucleotides. These peptides share sequence similarity with a region in DNA polymerase β that has been implicated in the binding of DNA template

  20. Imidazopyridine and Pyrazolopiperidine Derivatives as Novel Inhibitors of Serine Palmitoyl Transferase.

    Science.gov (United States)

    Genin, Michael J; Gonzalez Valcarcel, Isabel C; Holloway, William G; Lamar, Jason; Mosior, Marian; Hawkins, Eric; Estridge, Thomas; Weidner, Jeffrey; Seng, Thomas; Yurek, David; Adams, Lisa A; Weller, Jennifer; Reynolds, Vincent L; Brozinick, Joseph T

    2016-06-23

    To develop novel treatments for type 2 diabetes and dyslipidemia, we pursued inhibitors of serine palmitoyl transferase (SPT). To this end compounds 1 and 2 were developed as potent SPT inhibitors in vitro. 1 and 2 reduce plasma ceramides in rodents, have a slight trend toward enhanced insulin sensitization in DIO mice, and reduce triglycerides and raise HDL in cholesterol/cholic acid fed rats. Unfortunately these molecules cause a gastric enteropathy after chronic dosing in rats.

  1. From glutathione transferase to pore in a CLIC

    CERN Document Server

    Cromer, B A; Morton, C J; Parker, M W; 10.1007/s00249-002-0219-1

    2002-01-01

    Many plasma membrane chloride channels have been cloned and characterized in great detail. In contrast, very little is known about intracellular chloride channels. Members of a novel class of such channels, called the CLICs (chloride intracellular channels), have been identified over the last few years. A striking feature of the CLIC family of ion channels is that they can exist in a water- soluble state as well as a membrane-bound state. A major step forward in understanding the functioning of these channels has been the recent crystal structure determination of one family member, CLIC1. The structure confirms that CLICs are members of the glutathione S- transferase superfamily and provides clues as to how CLICs can insert into membranes to form chloride channels. (69 refs).

  2. Hepatitis C virus NS5A protein is a substrate for the peptidyl-prolyl cis/trans isomerase activity of cyclophilins A and B.

    Science.gov (United States)

    Hanoulle, Xavier; Badillo, Aurélie; Wieruszeski, Jean-Michel; Verdegem, Dries; Landrieu, Isabelle; Bartenschlager, Ralf; Penin, François; Lippens, Guy

    2009-05-15

    We report here a biochemical and structural characterization of domain 2 of the nonstructural 5A protein (NS5A) from the JFH1 Hepatitis C virus strain and its interactions with cyclophilins A and B (CypA and CypB). Gel filtration chromatography, circular dichroism spectroscopy, and finally NMR spectroscopy all indicate the natively unfolded nature of this NS5A-D2 domain. Because mutations in this domain have been linked to cyclosporin A resistance, we used NMR spectroscopy to investigate potential interactions between NS5A-D2 and cellular CypA and CypB. We observed a direct molecular interaction between NS5A-D2 and both cyclophilins. The interaction surface on the cyclophilins corresponds to their active site, whereas on NS5A-D2, it proved to be distributed over the many proline residues of the domain. NMR heteronuclear exchange spectroscopy yielded direct evidence that many proline residues in NS5A-D2 form a valid substrate for the enzymatic peptidyl-prolyl cis/trans isomerase (PPIase) activity of CypA and CypB.

  3. Linezolid and tiamulin cross-resistance in Staphylococcus aureus mediated by point mutations in the peptidyl transferase center.

    Science.gov (United States)

    Miller, Keith; Dunsmore, Colin J; Fishwick, Colin W G; Chopra, Ian

    2008-05-01

    Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of Staphylococcus aureus resistant to linezolid were selected and found to exhibit cross-resistance to tiamulin, a member of the pleuromutilin class of antibiotics. However, resistance was unidirectional because mutants of S. aureus selected for resistance to tiamulin did not exhibit cross-resistance to linezolid. This contrasts with the recently described PhLOPS(A) phenotype, which confers resistance to both oxazolidinones and pleuromutilins. The genotypes responsible for the phenotypes we observed were examined. Selection with tiamulin resulted in recovery of mutants with changes in the single-copy rplC gene (Gly155Arg, Ser158Leu, or Arg149Ser), whereas selection with linezolid led to recovery of mutants with changes (G2576U in 23S rRNA) in all five copies of the multicopy operon rrn. In contrast, cross-resistance to linezolid was exhibited by tiamulin-resistant mutants generated in a single-copy rrn knockout strains of Escherichia coli, illustrating that the copy number of 23S rRNA is the limiting factor in the selection of 23S rRNA tiamulin-resistant mutants. The interactions of linezolid and tiamulin with the ribosome were modeled to seek explanations for resistance to both classes in the 23S rRNA mutants and the lack of cross-resistance between tiamulin and linezolid following mutation in rplC.

  4. Primary overproduction of urate caused by a partial deficiency of hypoxanthine-guanine phosphoribosyl transferase

    International Nuclear Information System (INIS)

    Cassidy, M.; Gregory, M.C.; Harley, E.H.

    1980-01-01

    Inherited enzyme deficiencies are found in a small proportion of patients with gout who produce an excess of uric acid. The clinical, biochemical and therapeutic aspects of a case of hyperuricaemia caused by an atypical mutant hypoxanthine-guanine phophoribosyl transferase are presented. Urate overproduction was moderate and controlled by allopurinol therapy

  5. Crystallization and preliminary X-ray diffraction analysis of a glutathione S-transferase from Xylella fastidiosa

    International Nuclear Information System (INIS)

    Garcia, Wanius; Travensolo, Regiane F.; Rodrigues, Nathalia C.; Muniz, João R. C.; Caruso, Célia S.; Lemos, Eliana G. M.; Araujo, Ana Paula U.; Carrilho, Emanuel

    2008-01-01

    Glutathione S-transferase from X. fastidiosa (xfGST) has been overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 2.23 Å. Glutathione S-transferases (GSTs) form a group of multifunctional isoenzymes that catalyze the glutathione-dependent conjugation and reduction reactions involved in the cellular detoxification of xenobiotic and endobiotic compounds. GST from Xylella fastidiosa (xfGST) was overexpressed in Escherichia coli and purified by conventional affinity chromatography. In this study, the crystallization and preliminary X-ray analysis of xfGST is described. The purified protein was crystallized by the vapour-diffusion method, producing crystals that belonged to the triclinic space group P1. The unit-cell parameters were a = 47.73, b = 87.73, c = 90.74 Å, α = 63.45, β = 80.66, γ = 94.55°. xfGST crystals diffracted to 2.23 Å resolution on a rotating-anode X-ray source

  6. Crystallization and preliminary X-ray diffraction analysis of a glutathione S-transferase from Xylella fastidiosa

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Wanius, E-mail: wanius@if.sc.usp.br [Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Travensolo, Regiane F. [Grupo de Bioanalítica, Microfabricação e Separações, Instituto de Química de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Rodrigues, Nathalia C.; Muniz, João R. C. [Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Caruso, Célia S. [Grupo de Bioanalítica, Microfabricação e Separações, Instituto de Química de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Lemos, Eliana G. M. [Laboratório de Bioquímica de Microrganismos e de Plantas, Departamento de Tecnologia, UNESP, Jaboticabal (Brazil); Araujo, Ana Paula U. [Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Carrilho, Emanuel, E-mail: wanius@if.sc.usp.br [Grupo de Bioanalítica, Microfabricação e Separações, Instituto de Química de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil)

    2008-02-01

    Glutathione S-transferase from X. fastidiosa (xfGST) has been overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 2.23 Å. Glutathione S-transferases (GSTs) form a group of multifunctional isoenzymes that catalyze the glutathione-dependent conjugation and reduction reactions involved in the cellular detoxification of xenobiotic and endobiotic compounds. GST from Xylella fastidiosa (xfGST) was overexpressed in Escherichia coli and purified by conventional affinity chromatography. In this study, the crystallization and preliminary X-ray analysis of xfGST is described. The purified protein was crystallized by the vapour-diffusion method, producing crystals that belonged to the triclinic space group P1. The unit-cell parameters were a = 47.73, b = 87.73, c = 90.74 Å, α = 63.45, β = 80.66, γ = 94.55°. xfGST crystals diffracted to 2.23 Å resolution on a rotating-anode X-ray source.

  7. Involvement of human glutathione S-transferase isoenzymes in the conjugation of cyclophosphamide metabolites with glutathione

    NARCIS (Netherlands)

    Dirven, H.A.A.M.; Ommen, B. van; Bladeren, P.J. van

    1994-01-01

    Alkylating agents can be detoxified by conjugation with glutathione (GSH). One of the physiological significances of this lies in the observation that cancer cells resistant to the cytotoxic effects of alkylating agents have higher levels of GSH and high glutathione S-transferase (GST) activity.

  8. Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability

    NARCIS (Netherlands)

    Willems, A.P.; Gundogdu, M.; Kempers, M.J.E.; Giltay, J.C.; Pfundt, R.P.; Elferink, M.; Loza, B.F.; Fuijkschot, J.; Ferenbach, A.T.; Gassen, K.L. van; Aalten, D.M.F. van; Lefeber, D.J.

    2017-01-01

    N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and

  9. Isolation and characterization of an auxin-inducible glutathione S-transferase gene of Arabidopsis thaliana

    NARCIS (Netherlands)

    Kop, D.A.M. van der; Schuyer, M.; Scheres, B.J.G.; Zaal, B.J. van der; Hooykaas, P.J.J.

    1996-01-01

    Genes homologous to the auxin-inducible Nt103 glutathione S-transferase (GST) gene of tobacco, were isolated from a genomic library of Arabidopsis thaliana. We isolated a λ clone containing an auxin-inducible gene, At103-1a, and part of a constitutively expressed gene, At103-1b. The coding regions

  10. Peptidyl-prolyl cis/trans-isomerase A1 (Pin1) is a target for modification by lipid electrophiles.

    Science.gov (United States)

    Aluise, Christopher D; Rose, Kristie; Boiani, Mariana; Reyzer, Michelle L; Manna, Joseph D; Tallman, Keri; Porter, Ned A; Marnett, Lawrence J

    2013-02-18

    Oxidation of membrane phospholipids is associated with inflammation, neurodegenerative disease, and cancer. Oxyradical damage to phospholipids results in the production of reactive aldehydes that adduct proteins and modulate their function. 4-Hydroxynonenal (HNE), a common product of oxidative damage to lipids, adducts proteins at exposed Cys, His, or Lys residues. Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (Pin1), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry resulted in detection of Michael adducts at the active site residues His-157 and Cys-113. Time and concentration dependencies indicate that Cys-113 is the primary site of HNE modification. Pin1 was adducted in MDA-MB-231 breast cancer cells treated with 8-alkynyl-HNE as judged by click chemistry conjugation with biotin followed by streptavidin-based pulldown and Western blotting with anti-Pin1 antibody. Furthermore, orbitrap MS data support the adduction of Cys-113 in the Pin1 active site upon HNE treatment of MDA-MB-231 cells. siRNA knockdown of Pin1 in MDA-MB-231 cells partially protected the cells from HNE-induced toxicity. Recent studies indicate that Pin1 is an important molecular target for the chemopreventive effects of green tea polyphenols. The present study establishes that it is also a target for electrophilic modification by products of lipid peroxidation.

  11. Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products

    NARCIS (Netherlands)

    Rompelberg, C.J.M.; Ploemen, J.H.T.M.; Jespersen, S.; Greef, J. van der; Verhagen, H.; Bladeren, P.J. van

    1996-01-01

    The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme

  12. Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires

    Directory of Open Access Journals (Sweden)

    Pemberton Trevor J

    2006-09-01

    Full Text Available Abstract Background The peptidyl-prolyl cis/trans isomerase (PPIase class of proteins is present in all known eukaryotes, prokaryotes, and archaea, and it is comprised of three member families that share the ability to catalyze the cis/trans isomerisation of a prolyl bond. Some fungi have been used as model systems to investigate the role of PPIases within the cell, however how representative these repertoires are of other fungi or humans has not been fully investigated. Results PPIase numbers within these fungal repertoires appears associated with genome size and orthology between repertoires was found to be low. Phylogenetic analysis showed the single-domain FKBPs to evolve prior to the multi-domain FKBPs, whereas the multi-domain cyclophilins appear to evolve throughout cyclophilin evolution. A comparison of their known functions has identified, besides a common role within protein folding, multiple roles for the cyclophilins within pre-mRNA splicing and cellular signalling, and within transcription and cell cycle regulation for the parvulins. However, no such commonality was found with the FKBPs. Twelve of the 17 human cyclophilins and both human parvulins, but only one of the 13 human FKBPs, identified orthologues within these fungi. hPar14 orthologues were restricted to the Pezizomycotina fungi, and R. oryzae is unique in the known fungi in possessing an hCyp33 orthologue and a TPR-containing FKBP. The repertoires of Cryptococcus neoformans, Aspergillus fumigatus, and Aspergillus nidulans were found to exhibit the highest orthology to the human repertoire, and Saccharomyces cerevisiae one of the lowest. Conclusion Given this data, we would hypothesize that: (i the evolution of the fungal PPIases is driven, at least in part, by the size of the proteome, (ii evolutionary pressures differ both between the different PPIase families and the different fungi, and (iii whilst the cyclophilins and parvulins have evolved to perform conserved

  13. U2504 Determines the Species Specificity of the A-site Cleft Antibiotics. The Structures of Tiamulin, Homoharringtonine and Bruceantin Bound to the Ribosome

    Science.gov (United States)

    Gürel, Güliz; Blaha, Gregor; Moore, Peter B.; Steitz, Thomas A.

    2009-01-01

    Structures have been obtained for the complexes tiamulin, homoharringtonine and bruceatin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.8 to 3.2 Å. They show that these inhibitors all block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the A-site cleft in the peptidyl transferase center, which is universally conserved. In addition these structures support the hypothesis that the species-specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (E. coli). In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms. PMID:19362093

  14. Glutathione Transferases Superfamily: Cold-Inducible Expression of Distinct GST Genes in Brassica oleracea

    Directory of Open Access Journals (Sweden)

    Harshavardhanan Vijayakumar

    2016-07-01

    Full Text Available Plants, as sessile organisms, can suffer serious growth and developmental consequences under cold stress conditions. Glutathione transferases (GSTs, EC 2.5.1.18 are ubiquitous and multifunctional conjugating proteins, which play a major role in stress responses by preventing oxidative damage by reactive oxygen species (ROS. Currently, understanding of their function(s during different biochemical and signaling pathways under cold stress condition remain unclear. In this study, using combined computational strategy, we identified 65 Brassica oleracea glutathione transferases (BoGST and characterized them based on evolutionary analysis into 11 classes. Inter-species and intra-species duplication was evident between BoGSTs and Arabidopsis GSTs. Based on localization analyses, we propose possible pathways in which GST genes are involved during cold stress. Further, expression analysis of the predicted putative functions for GST genes were investigated in two cold contrasting genotypes (cold tolerance and susceptible under cold condition, most of these genes were highly expressed at 6 h and 1 h in the cold tolerant (CT and cold susceptible (CS lines, respectively. Overall, BoGSTU19, BoGSTU24, BoGSTF10 are candidate genes highly expressed in B. oleracea. Further investigation of GST superfamily in B. oleracea will aid in understanding complex mechanism underlying cold tolerance in plants.

  15. Changes in amino transferases and muscle proteins when treating pigmeat with ionising rays

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, R; Hofmann, K; Gruenewald, T; Partmann, W [Bundesanstalt fuer Fleischforschung, Kulmbach (F.R. Germany). Inst. fuer Chemie und Physik; Bundesforschungsanstalt fuer Ernaehrung, Karlsruhe [F.R. Germany

    1975-01-01

    Slices of lean pigmeat were treated with electron beams doses of 0.2, 1.0 and 5.0 Mrad. Low irradiation doses led to an increase in the activity of aspartate amino transferase (GOT) and alanin amino transferase (GPT) in the tissue generally and in the sarcoplasm (juice expressed from the muscle). 5 Mrad caused a great reduction in the activity of GOT and GPT in the tissue and the sarcoplasm. It seems doubtful whether this inactivation is due to a destruction of enzyme sulphhydryl groups. Irradiating with 5 Mrad resulted in partial release of the mitochondrial GOT isozyme (GOTsub(M)) into the sarcoplasm. This indicates damage to the mitochondrial membranes by ionising radiation. Irradiating the pigmeat increased the pH of the tissue and lowered its water binding ability (increase in drip). Up to a dose of 1 Mrad the solubility of the sarcoplasmic proteins was not definitely affected, but 5 Mrad caused a considerable drop in protein solubility. Surprisingly a dose of even 5 Mrad did not change the total number of sulphhydryl groups present in the tissue. Sephadex thin layer electrophoresis showed that at 0.2 Mrad there was a drastic decrease in the myosin band and an increase in peptide fragments of low molecular weight, whilst actin was little changed.

  16. Peptidyl aldehyde NK-1.8k suppresses enterovirus 71 and enterovirus 68 infection by targeting protease 3C.

    Science.gov (United States)

    Wang, Yaxin; Yang, Ben; Zhai, Yangyang; Yin, Zheng; Sun, Yuna; Rao, Zihe

    2015-05-01

    Enterovirus (EV) is one of the major causative agents of hand, foot, and mouth disease in the Pacific-Asia region. In particular, EV71 causes severe central nervous system infections, and the fatality rates from EV71 infection are high. Moreover, an outbreak of respiratory illnesses caused by an emerging EV, EV68, recently occurred among over 1,000 young children in the United States and was also associated with neurological infections. Although enterovirus has emerged as a considerable global public health threat, no antiviral drug for clinical use is available. In the present work, we screened our compound library for agents targeting viral protease and identified a peptidyl aldehyde, NK-1.8k, that inhibits the proliferation of different EV71 strains and one EV68 strain and that had a 50% effective concentration of 90 nM. Low cytotoxicity (50% cytotoxic concentration, >200 μM) indicated a high selective index of over 2,000. We further characterized a single amino acid substitution inside protease 3C (3C(pro)), N69S, which conferred EV71 resistance to NK-1.8k, possibly by increasing the flexibility of the substrate binding pocket of 3C(pro). The combination of NK-1.8k and an EV71 RNA-dependent RNA polymerase inhibitor or entry inhibitor exhibited a strong synergistic anti-EV71 effect. Our findings suggest that NK-1.8k could potentially be developed for anti-EV therapy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. A model to environmental monitoring based on glutathione-S-transferase activity and branchial lesions in catfish

    Science.gov (United States)

    Neta, Raimunda Nonata Fortes Carvalho; Torres, Audalio Rebelo

    2017-11-01

    In this work, we validate the glutathione-S-transferase and branchial lesions as biomarkers in catfish Sciades herzbergii to obtain a predictive model of the environmental impact effects in a harbor of Brazil. The catfish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in São Marcos Bay, Maranhão. Two biomarkers, hepatic glutathione S-transferase (GST) activity and branchial lesions were analyzed. The values for GST activity were modeled with the occurrence of branchial lesions by fitting a third order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial lesions in both the wet and the dry seasons, but only at the polluted port site. Our mathematic model indicates that when the GST ceases to act, serious branchial lesions are observed in the catfish of the contaminated port area.

  18. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver.

    NARCIS (Netherlands)

    Oetari, S.; Sudibyo, M.; Commandeur, J.N.M.; Samhoedi, R.; Vermeulen, N.P.E.

    1996-01-01

    The stability of curcumin, as well as the interactions between curcumin and cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The stability of curcumin was strongly improved by lowering the pH or

  19. Manche centre

    International Nuclear Information System (INIS)

    1997-05-01

    After a general presentation of radioactivity and radioactive wastes and of the French national agency for the management of radioactive wastes (ANDRA), this brochure gives a general overview of the Manche low- and medium-level radioactive waste disposal centre: principles of storage safety, waste containers (first confinement barrier), storage facility and cover (second confinement barrier), the underground (third confinement barrier), the impact of the centre on its environment, and the control of radioactivity in the vicinity of the centre. (J.S.)

  20. The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

    DEFF Research Database (Denmark)

    Rivas, Matilde De Las; Lira-Navarrete, Erandi; Daniel, Earnest James Paul

    2017-01-01

    The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- A nd/or C-terminal prior glycosylation ...

  1. Glutathione S-transferase M1 and T1, CYP1A2-2467T/delT ...

    African Journals Online (AJOL)

    The present study investigated the impact of metabolic gene polymorphisms in modulating lung cancer risk susceptibility. Gene polymorphisms encoding Cytochrome 1A2 (CYP1A2) and Glutathione-S-transferases (GSTT1 and GSTM1) are involved in the bioactivation and detoxification of tobacco carcinogens and may ...

  2. Linezolid and Tiamulin Cross-Resistance in Staphylococcus aureus Mediated by Point Mutations in the Peptidyl Transferase Center ▿

    Science.gov (United States)

    Miller, Keith; Dunsmore, Colin J.; Fishwick, Colin W. G.; Chopra, Ian

    2008-01-01

    Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of Staphylococcus aureus resistant to linezolid were selected and found to exhibit cross-resistance to tiamulin, a member of the pleuromutilin class of antibiotics. However, resistance was unidirectional because mutants of S. aureus selected for resistance to tiamulin did not exhibit cross-resistance to linezolid. This contrasts with the recently described PhLOPSA phenotype, which confers resistance to both oxazolidinones and pleuromutilins. The genotypes responsible for the phenotypes we observed were examined. Selection with tiamulin resulted in recovery of mutants with changes in the single-copy rplC gene (Gly155Arg, Ser158Leu, or Arg149Ser), whereas selection with linezolid led to recovery of mutants with changes (G2576U in 23S rRNA) in all five copies of the multicopy operon rrn. In contrast, cross-resistance to linezolid was exhibited by tiamulin-resistant mutants generated in a single-copy rrn knockout strains of Escherichia coli, illustrating that the copy number of 23S rRNA is the limiting factor in the selection of 23S rRNA tiamulin-resistant mutants. The interactions of linezolid and tiamulin with the ribosome were modeled to seek explanations for resistance to both classes in the 23S rRNA mutants and the lack of cross-resistance between tiamulin and linezolid following mutation in rplC. PMID:18180348

  3. Linezolid and Tiamulin Cross-Resistance in Staphylococcus aureus Mediated by Point Mutations in the Peptidyl Transferase Center ▿

    OpenAIRE

    Miller, Keith; Dunsmore, Colin J.; Fishwick, Colin W. G.; Chopra, Ian

    2008-01-01

    Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of Staphylococcus aureus resistant to linezolid were selected and found to exhibit cross-resistance to tiamulin, a member of the pleuromutilin class of an...

  4. Cloning and characterization of a glutathione S-transferase homologue from the plant pathogenic fungus Botrytis cinerea

    NARCIS (Netherlands)

    Prins, T.W.; Wagemakers, L.; Schouten, A.; Kan, van J.A.L.

    2000-01-01

    A gene was cloned from Botrytis cinerea that encodes a protein homologous to glutathione S-transferase (GST). The gene, denominated Bcgst1, is present in a single copy and represents the first example of such a gene from a filamentous fungus. The biochemical function of GSTs is to conjugate toxic

  5. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels: Evidence for correlated genetic effects

    NARCIS (Netherlands)

    van Beek, J.H.D.A.; de Moor, M.H.M.; Geels, L.M.; Sinke, M.R.T.; de Geus, E.J.C.; Lubke, G.H.; Kluft, C.; Neuteboom, J.; Vink, J.M.; Willemsen, G.; Boomsma, D.I.

    2014-01-01

    Background: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT

  6. The ideal Atomic Centre; Le Centre Atomique ideal

    Energy Technology Data Exchange (ETDEWEB)

    Mas, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1965-07-01

    The author presents considerations which should prove to be of interest to all those who have to design, to construct and to operate a nuclear research centre. A large number of the ideas presented can also be applied to non-nuclear scientific research centres. In his report the author reviews: various problems with which the constructor is faced: ground-plan, infrastructure, buildings and the large units of scientific equipment in the centre, and those problems facing the director: maintenance, production, supplies, security. The author stresses the relationship which ought to exist between the research workers and the management. With this aim in view he proposes the creation of National School for Administration in Research which would train administrative executives for public or private organisations; they would be specialised in the fields of fundamental or applied research. (author) [French] L'auteur propose une base de reflexions a tous ceux qui doivent concevoir, realiser et faire vivre un Centre d'Etudes Nucleaires. Un grand nombre des idees exprimees peut d'ailleurs s'appliquer a un Centre d'Etudes Scientifiques non nucleaires. Dans son ouvrage, l'auteur passe en revue les differents problemes qui se posent au constructeur: plan, masse, infrastructure, batiments et grands appareils du Centre, et ceux qu'a a resoudre le directeur: entretien, fabrication, approvisionnements, securite. L'auteur insiste sur l'aspect des rapports qui doivent exister entre les chercheurs et ceux qui les administrent. Il propose a cette fin la creation d'une Ecole Nationale d'Administration de la Recherche qui formerait des cadres administratifs pour les organismes publics ou prives, specialises dans la Recherche fondamentale ou appliquee. (auteur)

  7. Generation of Active Bovine Terminal Deoxynucleotidyl Transferase (TdT in E.coli

    Directory of Open Access Journals (Sweden)

    Wee Liang Kuan

    2010-08-01

    Full Text Available A synthetic gene encoding bovine terminal deoxynucleotidyl transferase (TdT was generated, cloned into an expression vector and expressed in E.coli. The effects of altering culture and induction conditions on the nature of recombinant protein production were investigated. This led to the expression of active recombinant bovine TdT in E.coli. After purification and characterisation, the activity of the enzyme was assessed in a biological assay for apoptosis. The process described in this report enables the economical production of TdT for high throughput applications.

  8. Generation of Active Bovine Terminal Deoxynucleotidyl Transferase (TdT in E.coli

    Directory of Open Access Journals (Sweden)

    Wee Liang Kuan

    2010-01-01

    Full Text Available A synthetic gene encoding bovine terminal deoxynucleotidyl transferase (TdT was generated, cloned into an expression vector and expressed in E.coli. The effects of altering culture and induction conditions on the nature of recombinant protein production were investigated. This led to the expression of active recombinant bovine TdT in E.coli. After purification and characterisation, the activity of the enzyme was assessed in a biological assay for apoptosis. The process described in this report enables the economical production of TdT for high throughput applications.

  9. Caractérisation biochimique et fonctionnelle de glutathion-S-transferases (GSTs) chez Phanerochaete chrysosporium

    OpenAIRE

    Anak Ngadin , Andrew

    2011-01-01

    Phanerochaete chrysosporium is a ligninolytic fungus widely studied because of its capacities to degrade wood and xenobiotics through an extracellular enzymatic system. Its genome has been sequenced and has provided researchers with a complete inventory of the predicted proteins produced by this organism. This has allowed the description of many protein superfamilies. Among them, Glutathione S-transferases (GSTs) constitute a complex and widespread superfamily classified as enzymes of seconda...

  10. Neuroantibodies (NAB) in African-American Children: Associations with Gender, Glutathione-S-Transferase (GST)Pi Polymorphisms (SNP) and Heavy Metals

    Science.gov (United States)

    CONTACT (NAME ONLY): Hassan El-Fawal Abstract Details PRESENTATION TYPE: Platform or Poster CURRENT CATEGORY: Neurodegenerative Disease | Biomarkers | Neurotoxicity, Metals KEYWORDS: Autoantibodies, Glutathione-S-Transferase, DATE/TIME LAST MODIFIED: DATE/TIME SUBMITTED: Abs...

  11. Changes in amino transferases and muscle proteins when treating pigmeat with ionising rays

    International Nuclear Information System (INIS)

    Hamm, R.; Hofmann, K.; Gruenewald, T.; Partmann, W.

    1975-01-01

    Slices of lean pigmeat were treated with electron beams doses of 0.2, 1.0 and 5.0 Mrad. Low irradiation doses led to an increase in the activity of aspartate amino transferase (GOT) and alanin amino transferase (GPT) in the tissue generally and in the sarcoplasm (juice expressed from the muscle). 5 Mrad caused a great reduction in the activity of GOT and GPT in the tissue and the sarcoplasm. It seems doubtful whether this inactivation is due to a destruction of enzyme sulphhydryl groups. Irradiating with 5 Mrad resulted in partial release of the mitochondrial GOT isozyme (GOTsub(M)) into the sarcoplasm. This indicates damage to the mitochondrial membranes by ionising radiation. Irradiating the pigmeat increased the pH of the tissue and lowered its water binding ability (increase in drip). Up to a dose of 1 Mrad the solubility of the sarcoplasmic proteins was not definitely affected, but 5 Mrad caused a considerable drop in protein solubility. Surprisingly a dose of even 5 Mrad did not change the total number of sulphhydryl groups present in the tissue. Sephadex thin layer electrophoresis showed that at 0.2 Mrad there was a drastic decrease in the myosin band and an increase in peptide fragments of low molecular weight, whilst actin was little changed. (orig.) [de

  12. Canadian Irradiation Centre

    International Nuclear Information System (INIS)

    1987-05-01

    The Canadian Irradiation Centre is a non-profit cooperative project between Atomic Energy of Canada Limited, Radiochemical Company and Universite du Quebec, Institut Armand-Frappier, Centre for Applied Research in Food Science. The Centre's objectives are to develop, demonstrate and promote Canada's radiation processing technology and its applications by conducting applied research; training technical, professional and scientific personnel; educating industry and government; demonstrating operational and scientific procedures; developing processing procedures and standards, and performing product and market acceptance trials. This pamphlet outlines the history of radoation technology and the services offered by the Canadian Irradiation Centre

  13. Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

    DEFF Research Database (Denmark)

    Palner, Mikael; McCormick, Patrick; Parkes, Jun

    2010-01-01

    R-[(11)C]-SKF 82957 is a high-affinity and potent dopamine D(1) receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, f...

  14. CMS Centre at CERN

    CERN Multimedia

    2007-01-01

    A new "CMS Centre" is being established on the CERN Meyrin site by the CMS collaboration. It will be a focal point for communications, where physicists will work together on data quality monitoring, detector calibration, offline analysis of physics events, and CMS computing operations. Construction of the CMS Centre begins in the historic Proton Synchrotron (PS) control room. The historic Proton Synchrotron (PS) control room, Opened by Niels Bohr in 1960, will be reused by CMS to built its control centre. TThe LHC@FNAL Centre, in operation at Fermilab in the US, will work very closely with the CMS Centre, as well as the CERN Control Centre. (Photo Fermilab)The historic Proton Synchrotron (PS) control room is about to start a new life. Opened by Niels Bohr in 1960, the room will be reused by CMS to built its control centre. When finished, it will resemble the CERN Contro...

  15. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    OpenAIRE

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-01-01

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lac...

  16. Glutathione Transferase from Trichoderma virens Enhances Cadmium Tolerance without Enhancing Its Accumulation in Transgenic Nicotiana tabacum

    Science.gov (United States)

    Dixit, Prachy; Mukherjee, Prasun K.; Ramachandran, V.; Eapen, Susan

    2011-01-01

    Background Cadmium (Cd) is a major heavy metal pollutant which is highly toxic to plants and animals. Vast agricultural areas worldwide are contaminated with Cd. Plants take up Cd and through the food chain it reaches humans and causes toxicity. It is ideal to develop plants tolerant to Cd, without enhanced accumulation in the edible parts for human consumption. Glutathione transferases (GST) are a family of multifunctional enzymes known to have important roles in combating oxidative stresses induced by various heavy metals including Cd. Some GSTs are also known to function as glutathione peroxidases. Overexpression/heterologous expression of GSTs is expected to result in plants tolerant to heavy metals such as Cd. Results Here, we report cloning of a glutathione transferase gene from Trichoderma virens, a biocontrol fungus and introducing it into Nicotiana tabacum plants by Agrobacterium-mediated gene transfer. Transgenic nature of the plants was confirmed by Southern blot hybridization and expression by reverse transcription PCR. Transgene (TvGST) showed single gene Mendelian inheritance. When transgenic plants expressing TvGST gene were exposed to different concentrations of Cd, they were found to be more tolerant compared to wild type plants, with transgenic plants showing lower levels of lipid peroxidation. Levels of different antioxidant enzymes such as glutathione transferase, superoxide dismutase, ascorbate peroxidase, guiacol peroxidase and catalase showed enhanced levels in transgenic plants expressing TvGST compared to control plants, when exposed to Cd. Cadmium accumulation in the plant biomass in transgenic plants were similar or lower than wild-type plants. Conclusion The results of the present study suggest that transgenic tobacco plants expressing a Trichoderma virens GST are more tolerant to Cd, without enhancing its accumulation in the plant biomass. It should be possible to extend the present results to crop plants for developing Cd tolerance and

  17. Glutathione transferase from Trichoderma virens enhances cadmium tolerance without enhancing its accumulation in transgenic Nicotiana tabacum.

    Directory of Open Access Journals (Sweden)

    Prachy Dixit

    Full Text Available BACKGROUND: Cadmium (Cd is a major heavy metal pollutant which is highly toxic to plants and animals. Vast agricultural areas worldwide are contaminated with Cd. Plants take up Cd and through the food chain it reaches humans and causes toxicity. It is ideal to develop plants tolerant to Cd, without enhanced accumulation in the edible parts for human consumption. Glutathione transferases (GST are a family of multifunctional enzymes known to have important roles in combating oxidative stresses induced by various heavy metals including Cd. Some GSTs are also known to function as glutathione peroxidases. Overexpression/heterologous expression of GSTs is expected to result in plants tolerant to heavy metals such as Cd. RESULTS: Here, we report cloning of a glutathione transferase gene from Trichoderma virens, a biocontrol fungus and introducing it into Nicotiana tabacum plants by Agrobacterium-mediated gene transfer. Transgenic nature of the plants was confirmed by Southern blot hybridization and expression by reverse transcription PCR. Transgene (TvGST showed single gene Mendelian inheritance. When transgenic plants expressing TvGST gene were exposed to different concentrations of Cd, they were found to be more tolerant compared to wild type plants, with transgenic plants showing lower levels of lipid peroxidation. Levels of different antioxidant enzymes such as glutathione transferase, superoxide dismutase, ascorbate peroxidase, guiacol peroxidase and catalase showed enhanced levels in transgenic plants expressing TvGST compared to control plants, when exposed to Cd. Cadmium accumulation in the plant biomass in transgenic plants were similar or lower than wild-type plants. CONCLUSION: The results of the present study suggest that transgenic tobacco plants expressing a Trichoderma virens GST are more tolerant to Cd, without enhancing its accumulation in the plant biomass. It should be possible to extend the present results to crop plants for

  18. Distinction between the Cfr Methyltransferase Conferring Antibiotic Resistance and the Housekeeping RlmN Methyltransferase

    DEFF Research Database (Denmark)

    Atkinson, Gemma C; Hansen, Lykke H; Tenson, Tanel

    2013-01-01

    The cfr gene encodes the Cfr methyltransferase that primarily methylates C-8 in A2503 of 23S rRNA in the peptidyl transferase region of bacterial ribosomes. The methylation provides resistance to six classes of antibiotics of clinical and veterinary importance. The rlmN gene encodes the Rlm......N methyltransferase that methylates C-2 in A2503 in 23S rRNA and A37 in tRNA, but RlmN does not significantly influence antibiotic resistance. The enzymes are homologous and use the same mechanism involving radical S-adenosyl methionine to methylate RNA via an intermediate involving a methylated cysteine....... The differentiation between the two classes is supported by previous and new experimental evidence from antibiotic resistance, primer extensions, and mass spectrometry. Finally, evolutionary aspects of the distribution of Cfr- and RlmN-like enzymes are discussed....

  19. Human-centred Governance

    DEFF Research Database (Denmark)

    Bason, Christian

    2017-01-01

    Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

  20. Glutathione-binding site of a bombyx mori theta-class glutathione transferase.

    Directory of Open Access Journals (Sweden)

    M D Tofazzal Hossain

    Full Text Available The glutathione transferase (GST superfamily plays key roles in the detoxification of various xenobiotics. Here, we report the isolation and characterization of a silkworm protein belonging to a previously reported theta-class GST family. The enzyme (bmGSTT catalyzes the reaction of glutathione with 1-chloro-2,4-dinitrobenzene, 1,2-epoxy-3-(4-nitrophenoxy-propane, and 4-nitrophenethyl bromide. Mutagenesis of highly conserved residues in the catalytic site revealed that Glu66 and Ser67 are important for enzymatic function. These results provide insights into the catalysis of glutathione conjugation in silkworm by bmGSTT and into the metabolism of exogenous chemical agents.

  1. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target.

    Directory of Open Access Journals (Sweden)

    Katharine S Dobb

    Full Text Available Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds.

  2. Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

    Science.gov (United States)

    POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

    2015-01-01

    Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

  3. The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation

    DEFF Research Database (Denmark)

    Wandall, Hans H; Irazoqui, Fernando; Tarp, Mads Agervig

    2007-01-01

    Initiation of mucin-type O-glycosylation is controlled by a large family of UDP GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Most GalNAc-transferases contain a ricin-like lectin domain in the C-terminal end, which may confer GalNAc-glycopeptide substrate specificit...

  4. Miopatia por deficiência de carnitina-palmitil-transferase: relato de 2 casos com dosagens enzimáticas no tecido muscular

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1983-12-01

    Full Text Available Relato dos casos de dois irmãos, que desde a infância apresentavam dores musculares após exercício prolongado ou exposição ao frio, com diminuição da força, à medida que o exercício continuava. Um deles desenvolveu mioglobinúria recorrente e, em um episódio apresentou insuficiência renal aguda, necessitando de diálise peritonial. A investigação laboratorial intercrise foi normal, mas durante o episódio de mioglobinúria, apresentou grande aumento da creatinafosfoquinase. A eletromiografia foi sugestiva de processo de denervação. Teste de produção de lactato durante isquemia foi normal. Biópsias musculares mostraram discreto aumento dos lipídios nas fibras musculares e maior atividade da desidrogenase succínica na histoquímica. O estudo bioquímico do tecido muscular dos dois pacientes, revelou importante redução da atividade da carnitina-palmitil-transferase, com atividade normal da carnitina-octanoil-transferase e carnitina-acetil-transferase. São discutidas as vias metabólicas, sua importância na manutenção da energia muscular durante o exercício prolongado e o papel dos ácidos graxos como fonte energética muscular durante condições normais e patológicas.

  5. Evaluation of antioxidant and antimicrobial activity of seaweed ( Sargassum sp.) extract: A study on inhibition of glutathione-S-transferase Activity

    Digital Repository Service at National Institute of Oceanography (India)

    Patra, J.K.; Rath, S.K.; Jena, K.B.; Rathod, V.K.; Thatoi, H.

    In the present study, the free radical scavenging potentials (DPPH radical and hydroxyl radical), inhibition of lipid peroxidation, and glutathione-S-transferase and antimicrobial properties of Sargassum sp. extract were investigated. The tested...

  6. RTEMS Centre - Support and Maintenance Centre to RTEMS Operating System

    Science.gov (United States)

    Silva, H.; Constantino, A.; Freitas, D.; Coutinho, M.; Faustino, S.; Mota, M.; Colaço, P.; Sousa, J.; Dias, L.; Damjanovic, B.; Zulianello, M.; Rufino, J.

    2009-05-01

    RTEMS CENTRE - Support and Maintenance Centre to RTEMS Operating System is a joint ESA/Portuguese Task Force initiative to develop a support and maintenance centre to the Real-Time Executive for Multiprocessor Systems (RTEMS). This paper gives a high level visibility of the progress, the results obtained and the future work in the RTEMS CENTRE [6] and in the RTEMS Improvement [7] projects. RTEMS CENTRE started officially in November 2006, with the RTEMS 4.6.99.2 version. A full analysis of RTEMS operating system was produced. The architecture was analysed in terms of conceptual, organizational and operational concepts. The original objectives [1] of the centre were primarily to create and maintain technical expertise and competences in this RTOS, to develop a website to provide the European Space Community an entry point for obtaining support (http://rtemscentre.edisoft.pt), to design, develop, maintain and integrate some RTEMS support tools (Timeline Tool, Configuration and Management Tools), to maintain flight libraries and Board Support Packages, to develop a strong relationship with the World RTEMS Community and finally to produce some considerations in ARINC-653, DO-178B and ECSS E-40 standards. RTEMS Improvement is the continuation of the RTEMS CENTRE. Currently the RTEMS, version 4.8.0, is being facilitated for a future qualification. In this work, the validation material is being produced following the Galileo Software Standards Development Assurance Level B [5]. RTEMS is being completely tested, errors analysed, dead and deactivated code removed and tests produced to achieve 100% statement and decision coverage of source code [2]. The SW to exploit the LEON Memory Management Unit (MMU) hardware will be also added. A brief description of the expected implementations will be given.

  7. Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age X SNP interaction and Cardiometabolic Disease Associations

    NARCIS (Netherlands)

    Middelberg, R.P.S.; Benyamin, B.; de Moor, M.H.M.; Warrington, N.M.; Gordon, S.; Henders, A.K.; Medland, S.E.; Nyholt, DR; de Geus, E.J.C.; Hottenga, J.J.; Willemsen, G.; Beilin, L.J.; Mori, T.A.; Wright, M.J.; Heath, A.C.; Madden, P.A.F.; Boomsma, D.I.; Pennell, C.E.; Montgomery, G.W.; Martin, N.G.; Whitfield, J.B.

    2012-01-01

    Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in

  8. The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function

    International Nuclear Information System (INIS)

    Achilonu, Ikechukwu; Gildenhuys, Samantha; Fisher, Loren; Burke, Jonathan; Fanucchi, Sylvia; Sewell, B. Trevor; Fernandes, Manuel; Dirr, Heini W.

    2010-01-01

    The role of a topologically conserved isoleucine in the structure of glutathione transferase was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The common fold shared by members of the glutathione-transferase (GST) family has a topologically conserved isoleucine residue at the N-terminus of helix 3 which is involved in the packing of helix 3 against two β-strands in domain 1. The role of the isoleucine residue in the structure, function and stability of GST was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The X-ray structures of the I71A and I71V mutants resolved at 1.75 and 2.51 Å, respectively, revealed that the mutations do not alter the overall structure of the protein compared with the wild type. Urea-induced equilibrium unfolding studies using circular dichroism and tryptophan fluorescence suggest that the mutation of Ile71 to alanine or valine reduces the stability of the protein. A functional assay with 1-chloro-2,4-dinitrobenzene shows that the mutation does not significantly alter the function of the protein relative to the wild type. Overall, the results suggest that conservation of the topologically conserved Ile71 maintains the structural stability of the protein but does not play a significant role in catalysis and substrate binding

  9. Birth centre confinement at the Queen Victoria Medical Centre. I. Obstetric and neonatal outcome.

    Science.gov (United States)

    Campbell, J; Hudson, H; Lumley, J; Morris, N; Rao, J; Spensley, J

    1981-10-03

    A review of hte first 175 confinements at the Queen Victoria Medical Centre Birth Centre is presented. The design, structure and function of hte Birth Centre is described and the safety of the programme demonstrated. Seventy-four pregnancies (42%) accepted for Birth Centre confinement required transfer because of antepartum or intrapartum complications. There were satisfactory obstetric and neonatal outcomes in all pregnancies. The first year's experience has allowed a reassessment of the risk factors, which will permit greater use of the Birth Centre without any increases risk to mothers or babies.

  10. Proline substitutions in a Mip-like peptidyl-prolyl cis-trans isomerase severely affect its structure, stability, shape and activity

    Directory of Open Access Journals (Sweden)

    Soumitra Polley

    2015-01-01

    Full Text Available FKBP22, an Escherichia coli-specific peptidyl-prolyl cis-trans isomerase, shows substantial homology with the Mip-like virulence factors. Mip-like proteins are homodimeric and possess a V-shaped conformation. Their N-terminal domains form dimers, whereas their C-terminal domains bind protein/peptide substrates and distinct inhibitors such as rapamycin and FK506. Interestingly, the two domains of the Mip-like proteins are separated by a lengthy, protease-susceptible α-helix. To delineate the structural requirement of this domain-connecting region in Mip-like proteins, we have investigated a recombinant FKBP22 (rFKBP22 and its three point mutants I65P, V72P and A82P using different probes. Each mutant harbors a Pro substitution mutation at a distinct location in the hinge region. We report that the three mutants are not only different from each other but also different from rFKBP22 in structure and activity. Unlike rFKBP22, the three mutants were unfolded by a non-two state mechanism in the presence of urea. In addition, the stabilities of the mutants, particularly I65P and V72P, differed considerably from that of rFKBP22. Conversely, the rapamycin binding affinity of no mutant was different from that of rFKBP22. Of the mutants, I65P showed the highest levels of structural/functional loss and dissociated partly in solution. Our computational study indicated a severe collapse of the V-shape in I65P due to the anomalous movement of its C-terminal domains. The α-helical nature of the domain-connecting region is, therefore, critical for the Mip-like proteins.

  11. The Search for Centre

    Science.gov (United States)

    Nunes, April

    2006-01-01

    This paper acknowledges the importance of a dancer's centre but likewise highlights the problematic nature of the communication of this concept from dance teacher to student. After a brief introduction of orthodox approaches in finding centre, this paper suggests a method of locating centre through the ancient somatic technique.

  12. Two pear glutathione S-transferases genes are regulated during fruit development and involved in response to salicylic acid, auxin, and glucose signaling.

    Directory of Open Access Journals (Sweden)

    Hai-Yan Shi

    Full Text Available Two genes encoding putative glutathione S-transferase proteins were isolated from pear (Pyrus pyrifolia and designated PpGST1 and PpGST2. The deduced PpGST1 and PpGST2 proteins contain conserved Glutathione S-transferase N-terminal domain (GST_N and Glutathione S-transferase, C-terminal domain (GST_C. Using PCR amplification technique, the genomic clones corresponding to PpGST1 and PpGST2 were isolated and shown to contain two introns and a singal intron respectively with typical GT/AG boundaries defining the splice junctions. Phylogenetic analysis clearly demonstrated that PpGST1 belonged to Phi class of GST superfamilies and had high homology with apple MdGST, while PpGST2 was classified into the Tau class of GST superfamilies. The expression of PpGST1 and PpGST2 genes was developmentally regulated in fruit. Further study demonstrated that PpGST1 and PpGST2 expression was remarkably induced by glucose, salicylic acid (SA and indole-3-aceticacid (IAA treatments in pear fruit, and in diseased fruit. These data suggested that PpGST1 and PpGST2 might be involved in response to sugar, SA, and IAA signaling during fruit development of pear.

  13. The Aube centre; Le Centre de l`Aube

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    This educational booklet is devoted to a general presentation of the Aube radioactive wastes storage centre. After a short presentation of the Andra, the French national agency for the management of radioactive wastes, it gives some general information about radioactive wastes (origin, classification), containers (quality assurance and different types), wastes transportation (planning, safety), and about the Aube centre itself: description, treatment and conditioning of drums (compacting and injection), storage facilities, geological situation of the site, and environmental controls. (J.S.)

  14. T-2 Toxin-induced Toxicity in Pregnant Mice and Rats

    Directory of Open Access Journals (Sweden)

    Shinya Sehata

    2008-11-01

    Full Text Available T-2 toxin is a cytotoxic secondary fungal metabolite that belongs to the trichothecene mycotoxin family. This mycotoxin is a well known inhibitor of protein synthesis through its high binding affinity to peptidyl transferase, which is an integral part of the ribosomal 60s subunit, and it also inhibits the synthesis of DNA and RNA, probably secondary to the inhibition of protein synthesis. In addition, T-2 toxin is said to induce apoptosis in many types of cells bearing high proliferating activity. T-2 toxin readily passes the placenta and is distributed to embryo/fetal tissues, which include many component cells bearing high proliferating activity. This paper reviews the reported data related to T-2 toxin-induced maternal and fetal toxicities in pregnant mice and rats. The mechanisms of T-2 toxin-induced apoptosis in maternal and fetal tissues are also discussed in this paper.

  15. Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

    DEFF Research Database (Denmark)

    Long, Katherine S.; Vester, Birte

    2012-01-01

    Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant Gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations...... to the linezolid binding site, so this review will therefore focus on the various changes that can adversely affect drug binding and confer resistance. High-resolution structures of linezolid bound to the 50S ribosomal subunit show that it binds in a deep cleft that is surrounded by 23S rRNA nucleotides. Mutation...... of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away from the bound drug, mutations in specific regions of these proteins are increasingly being associated with linezolid resistance. However, very little...

  16. Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

    Science.gov (United States)

    Matsumoto, M; Imagawa, M; Aoki, Y

    2000-07-01

    Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did not stimulate GPEI-mediated gene expression. On the other hand, the antioxidant reagents butylhydroxyanisole and t-butylhydroquinone, stimulated GPEI-mediated gene expression, but the level of GSTP1 mRNA was not elevated. Our observations suggest that EGF and TGF alpha induce GSTP1 by the same signal transduction pathway as PenCB. Since the sequence of GPEI is similar to that of the antioxidant responsive element (ARE), some factors which bind to ARE might play a role in GPEI-mediated gene expression.

  17. Client Centred Desing

    DEFF Research Database (Denmark)

    Ørngreen, Rikke; Nielsen, Janni; Levinsen, Karin

    2008-01-01

    In this paper we argue for the use of Client Centred preparation phases when designing complex systems. Through Client Centred Design human computer interaction can extend the focus on end-users to alse encompass the client's needs, context and resources....

  18. Function and phylogeny of bacterial butyryl-CoA:acetate transferases and their diversity in the proximal colon of swine

    Science.gov (United States)

    Studying the host-associated butyrate-producing bacterial community is important because butyrate is essential for colonic homeostasis and gut health. Previous research has identified the butyryl-coA:acetate transferase (2.3.8.3) as a the main gene for butyrate production in intestinal ecosystems; h...

  19. SAP Nuclear Competence Centre

    International Nuclear Information System (INIS)

    Andrlova, Z.

    2009-01-01

    In this issue we continue and introduce the SAP Nuclear Competence Centre and its head Mr. Igor Dzama. SAP Nuclear Competence Centrum is one of the fi rst competence centres outside ENEL headquarters. It should operate in Slovakia and should have competencies within the whole Enel group. We are currently dealing with the issues of organisation and funding. We are trying to balance the accountability to the NPP directors and to the management of the competence centres at Enel headquarters; we are looking at the relations between the competence centres within the group and defining the services that we will provide for the NPPs. author)

  20. Large-scale fuel cycle centres

    International Nuclear Information System (INIS)

    Smiley, S.H.; Black, K.M.

    1977-01-01

    The US Nuclear Regulatory Commission (NRC) has considered the nuclear energy centre concept for fuel cycle plants in the Nuclear Energy Centre Site Survey 1975 (NECSS-75) Rep. No. NUREG-0001, an important study mandated by the US Congress in the Energy Reorganization Act of 1974 which created the NRC. For this study, the NRC defined fuel cycle centres as consisting of fuel reprocessing and mixed-oxide fuel fabrication plants, and optional high-level waste and transuranic waste management facilities. A range of fuel cycle centre sizes corresponded to the fuel throughput of power plants with a total capacity of 50,000-300,000MW(e). The types of fuel cycle facilities located at the fuel cycle centre permit the assessment of the role of fuel cycle centres in enhancing the safeguard of strategic special nuclear materials - plutonium and mixed oxides. Siting fuel cycle centres presents a smaller problem than siting reactors. A single reprocessing plant of the scale projected for use in the USA (1500-2000t/a) can reprocess fuel from reactors producing 50,000-65,000MW(e). Only two or three fuel cycle centres of the upper limit size considered in the NECSS-75 would be required in the USA by the year 2000. The NECSS-75 fuel cycle centre evaluation showed that large-scale fuel cycle centres present no real technical siting difficulties from a radiological effluent and safety standpoint. Some construction economies may be achievable with fuel cycle centres, which offer opportunities to improve waste-management systems. Combined centres consisting of reactors and fuel reprocessing and mixed-oxide fuel fabrication plants were also studied in the NECSS. Such centres can eliminate shipment not only of Pu but also mixed-oxide fuel. Increased fuel cycle costs result from implementation of combined centres unless the fuel reprocessing plants are commercial-sized. Development of Pu-burning reactors could reduce any economic penalties of combined centres. The need for effective fissile

  1. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    Energy Technology Data Exchange (ETDEWEB)

    Sakaidani, Yuta [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichiyanagi, Naoki [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Saito, Chika; Nomura, Tomoko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ito, Makiko [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Nishio, Yosuke [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Nadano, Daita; Matsuda, Tsukasa [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Furukawa, Koichi [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Okajima, Tetsuya, E-mail: tokajima@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer We characterized A130022J15Rik (Eogt1)-a mouse gene homologous to Drosophila Eogt. Black-Right-Pointing-Pointer Eogt1 encodes EGF domain O-GlcNAc transferase. Black-Right-Pointing-Pointer Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. Black-Right-Pointing-Pointer O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-{beta}-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  2. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    International Nuclear Information System (INIS)

    Sakaidani, Yuta; Ichiyanagi, Naoki; Saito, Chika; Nomura, Tomoko; Ito, Makiko; Nishio, Yosuke; Nadano, Daita; Matsuda, Tsukasa; Furukawa, Koichi; Okajima, Tetsuya

    2012-01-01

    Highlights: ► We characterized A130022J15Rik (Eogt1)—a mouse gene homologous to Drosophila Eogt. ► Eogt1 encodes EGF domain O-GlcNAc transferase. ► Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. ► O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  3. The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma

    DEFF Research Database (Denmark)

    Rogers, A J; Brasch-Andersen, C; Ionita-Laza, I

    2009-01-01

    BACKGROUND: The glutathione S-transferase M1 (GSTM1)-null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress. OBJECTIVE: To exp...

  4. Effects of unstratified and centre-stratified randomization in multi-centre clinical trials.

    Science.gov (United States)

    Anisimov, Vladimir V

    2011-01-01

    This paper deals with the analysis of randomization effects in multi-centre clinical trials. The two randomization schemes most often used in clinical trials are considered: unstratified and centre-stratified block-permuted randomization. The prediction of the number of patients randomized to different treatment arms in different regions during the recruitment period accounting for the stochastic nature of the recruitment and effects of multiple centres is investigated. A new analytic approach using a Poisson-gamma patient recruitment model (patients arrive at different centres according to Poisson processes with rates sampled from a gamma distributed population) and its further extensions is proposed. Closed-form expressions for corresponding distributions of the predicted number of the patients randomized in different regions are derived. In the case of two treatments, the properties of the total imbalance in the number of patients on treatment arms caused by using centre-stratified randomization are investigated and for a large number of centres a normal approximation of imbalance is proved. The impact of imbalance on the power of the study is considered. It is shown that the loss of statistical power is practically negligible and can be compensated by a minor increase in sample size. The influence of patient dropout is also investigated. The impact of randomization on predicted drug supply overage is discussed. Copyright © 2010 John Wiley & Sons, Ltd.

  5. Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner

    Directory of Open Access Journals (Sweden)

    Ya Lin Zhang

    2013-03-01

    Full Text Available Previous investigations have implicated glutathione S-transferases (GSTs as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9 as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity.

  6. S-Nitrosation destabilizes glutathione transferase P1-1.

    Science.gov (United States)

    Balchin, David; Stoychev, Stoyan H; Dirr, Heini W

    2013-12-23

    Protein S-nitrosation is a post-translational modification that regulates the function of more than 500 human proteins. Despite its apparent physiological significance, S-nitrosation is poorly understood at a molecular level. Here, we investigated the effect of S-nitrosation on the activity, structure, stability, and dynamics of human glutathione transferase P1-1 (GSTP1-1), an important detoxification enzyme ubiquitous in aerobes. S-Nitrosation at Cys47 and Cys101 reduces the activity of the enzyme by 94%. Circular dichroism spectroscopy, acrylamide quenching, and amide hydrogen-deuterium exchange mass spectrometry experiments indicate that the loss of activity is caused by the introduction of local disorder at the active site of GSTP1-1. Furthermore, the modification destabilizes domain 1 of GSTP1-1 against denaturation, smoothing the unfolding energy landscape of the protein and introducing a refolding defect. In contrast, S-nitrosation at Cys101 alone introduces a refolding defect in domain 1 but compensates by stabilizing the domain kinetically. These data elucidate the physical basis for the regulation of GSTP1-1 by S-nitrosation and provide general insight into the consequences of S-nitrosation on protein stability and dynamics.

  7. Defining and describing birth centres in the Netherlands - a component study of the Dutch Birth Centre Study.

    Science.gov (United States)

    Hermus, M A A; Boesveld, I C; Hitzert, M; Franx, A; de Graaf, J P; Steegers, E A P; Wiegers, T A; van der Pal-de Bruin, K M

    2017-07-03

    During the last decade, a rapid increase of birth locations for low-risk births, other than conventional obstetric units, has been seen in the Netherlands. Internationally some of such locations are called birth centres. The varying international definitions for birth centres are not directly applicable for use within the Dutch obstetric system. A standard definition for a birth centre in the Netherlands is lacking. This study aimed to develop a definition of birth centres for use in the Netherlands, to identify these centres and to describe their characteristics. International definitions of birth centres were analysed to find common descriptions. In July 2013 the Dutch Birth Centre Questionnaire was sent to 46 selected Dutch birth locations that might qualify as birth centre. Questions included: location, reason for establishment, women served, philosophies, facilities that support physiological birth, hotel-facilities, management, environment and transfer procedures in case of referral. Birth centres were visited to confirm the findings from the Dutch Birth Centre Questionnaire and to measure distance and time in case of referral to obstetric care. From all 46 birth locations the questionnaires were received. Based on this information a Dutch definition of a birth centre was constructed. This definition reads: "Birth centres are midwifery-managed locations that offer care to low risk women during labour and birth. They have a homelike environment and provide facilities to support physiological birth. Community midwives take primary professional responsibility for care. In case of referral the obstetric caregiver takes over the professional responsibility of care." Of the 46 selected birth locations 23 fulfilled this definition. Three types of birth centres were distinguished based on their location in relation to the nearest obstetric unit: freestanding (n = 3), alongside (n = 14) and on-site (n = 6). Transfer in case of referral was necessary for all

  8. Succinyl-CoA:acetoacetate transferase deficiency: identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K. E.; Wanders, R. J.; Ruiter, J. P.; IJlst, L.; Visser, G.; Reitsma-Bierens, W. C.; Heymans, H. S.; Reijngoud, D. J.; Smit, G. P.

    1997-01-01

    We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis, and

  9. Succinyl-CoA:acetoacetate transferase deficiency : identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K E; Wanders, R J; Ruiter, J P; Ijlst, L; Visser, G; Reitsma-Bierens, W C; Heijmans, Hugo; Reijngoud, D J; Smit, G P

    1997-01-01

    UNLABELLED: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis,

  10. Succinyl-CoA:acetoacetate transferase deficiency : identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K E; Wanders, R J; Ruiter, J P; Ijlst, L; Visser, G; Reitsma-Bierens, W C; Heijmans, Hugo; Reijngoud, D J; Smit, G P

    UNLABELLED: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis,

  11. Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities.

    Science.gov (United States)

    Pushparajah, Daphnee S; Umachandran, Meera; Plant, Kathryn E; Plant, Nick; Ioannides, Costas

    2007-02-28

    The principal objective was to ascertain whether precision-cut tissue slices can be used to evaluate the potential of chemicals to induce CYP1, epoxide hydrolase and glutathione S-transferase activities, all being important enzymes involved in the metabolism of polycyclic aromatic hydrocarbons. Precision-cut rat liver and lung slices were incubated with a range of benzo[a]pyrene concentrations for various time periods. A rise in the O-deethylation of ethoxyresorufin was seen in both liver and lung slices exposed to benzo[a]pyrene, which was accompanied by increased CYP1A apoprotein levels. Pulmonary CYP1B1 apoprotein levels and hepatic mRNA levels were similarly enhanced. Elevated epoxide hydrolase and glutathione S-transferase activities were also observed in liver slices following incubation for 24h; similarly, a rise in apoprotein levels of both enzymes was evident, peak levels occurring at the same time point. When mRNA levels were monitored, a rise in the levels of both enzymes was seen as early as 4h after incubation, but maximum levels were attained at 24 h. In lung slices, induction of epoxide hydrolase by benzo[a]pyrene was observed after a 24-h incubation, and at a concentration of 1 microM; a rise in apoprotein levels was seen at this time point. Glutathione S-transferase activity was not inducible in lung slices by benzo[a]pyrene but a modest increase was observed in hepatic slices. Collectively, these studies confirmed CYP1A induction in rat liver slices and established that CYP1B1 expression, and epoxide hydrolase and glutathione S-transferase activities are inducible in precision-cut tissue slices.

  12. O-Glycosylation Modulates Proprotein Convertase Activation of Angiopoietin-like Protein 3: POSSIBLE ROLE OF POLYPEPTIDE GalNAc-TRANSFERASE-2 IN REGULATION OF CONCENTRATIONS OF PLASMA LIPIDS

    DEFF Research Database (Denmark)

    Schjoldager, Katrine Ter-Borch Gram; Vester-Christensen, Malene B; Bennett, Eric Paul

    2010-01-01

    immediately C-terminal (TT(226)). We developed an in vivo model system in CHO ldlD cells that was used to show that O-glycosylation in the processing site blocked processing of ANGPTL3. Genome-wide SNP association studies have identified the polypeptide GalNAc-transferase gene, GALNT2, as a candidate gene...... for low HDL and high triglyceride blood levels. We hypothesized that the GalNAc-T2 transferase performed critical O-glycosylation of proteins involved in lipid metabolism. Screening of a panel of proteins known to affect lipid metabolism for potential sites glycosylated by GalNAc-T2 led to identification...

  13. Birth centre confinement at the Queen Victoria Medical Centre: four years' experience.

    Science.gov (United States)

    Morris, N; Campbell, J; Biro, M A; Lumley, J; Rao, J; Spensley, J

    1986-06-09

    A review of the first four years of the functioning of the birth centre at the Queen Victoria Medical Centre is presented. In that time, 1040 pregnant women were accepted for confinement there. Of these, 52 withdrew for non-obstetric reasons, while 470 were transferred to alternative obstetrical care--274 because of antepartum complications and 196 because of intrapartum problems. Therefore, 518 women were delivered in the birth centre. The care of the women is entrusted almost entirely to a team of midwives and this review demonstrates an enviable safety record.

  14. The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients

    DEFF Research Database (Denmark)

    Buchard, Anders; Eefsen, Martin; Semb, Synne

    2012-01-01

    The aim of this study was to assess if genetic variants in the glutathione-S-transferase genes GST-T1, M1, and P1 reflect risk factors in acetaminophen (APAP)-poisoned patients assessed by investigation of the relation to prothrombin time (PT), which is a sensitive marker of survival in these pat...

  15. International research centre launched

    International Nuclear Information System (INIS)

    1965-01-01

    Full text: The first scientific research and educational institution to be set up on a completely international basis was officially inaugurated in Trieste on 5 October 1964 by the Director General of IAEA, Dr. Sigvard Eklund, when he opened the first seminar of the International Centre for Theoretical Physics. As evidence of the international nature of the institution he noted that the scientists who would work and teach there during the first year represented sixteen different countries. By the end of 1964, the Centre building was nearing completion and three of the five floors were occupied. A successful symposium had been held on the subject of plasma physics, and a score of professors and fellows were at work, from Bulgaria, Czechoslovakia, Greece, India, Japan, Jordan, the Netherlands, Norway, Pakistan, Poland, the United Kingdom, and the United States. A dozen scientific papers had been issued as preprints. The main purpose of the Centre is to foster the advancement of theoretical physics through training and research; at first the chief subject will be high-energy and elementary particle physics. Plasma physics, low energy physics and solid-state physics will also be dealt with. Special attention is paid to the needs of the developing countries. Of the 25 fellows selected for the academic year 1964-65, more than half are from South America, Africa and Asia. In conjunction with the Research Centre, there is an Advanced School for theoretical Physics to provide graduate training for fellows who need such preparation before they embark upon research. The Centre works under the guidance of a Scientific Council comprising the president, Prof. M. Sandoval-Vallarta (Nuclear Energy Commission of Mexico); Prof. A. Abragam (Saclay, France); Prof. R. Oppenheimer (Institute for Advanced Study, Princeton, USA); Dr. V. Soloviev (Dubna, USSR); Prof V.F. Weiskopf (Director General, CERN) ; Prof Abdus Salam (Imperial College, London) ; Prof. P. Budini (University of Trieste

  16. Effects of Deletion of the Streptococcus pneumoniae Lipoprotein Diacylglyceryl Transferase Gene lgt on ABC Transporter Function and on Growth In Vivo.

    NARCIS (Netherlands)

    Chimalapati, S.; Cohen, J.M.; Camberlein, E.; Macdonald, N.; Durmort, C.; Vernet, T.; Hermans, P.W.M.; Mitchell, T.; Brown, J.S.

    2012-01-01

    Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the

  17. The Fusarium oxysporum gnt2, encoding a putative N-acetylglucosamine transferase, is involved in cell wall architecture and virulence.

    Directory of Open Access Journals (Sweden)

    Loida López-Fernández

    Full Text Available With the aim to decipher the molecular dialogue and cross talk between Fusarium oxysporum f.sp. lycopersci and its host during infection and to understand the molecular bases that govern fungal pathogenicity, we analysed genes presumably encoding N-acetylglucosaminyl transferases, involved in glycosylation of glycoproteins, glycolipids, proteoglycans or small molecule acceptors in other microorganisms. In silico analysis revealed the existence of seven putative N-glycosyl transferase encoding genes (named gnt in F. oxysporum f.sp. lycopersici genome. gnt2 deletion mutants showed a dramatic reduction in virulence on both plant and animal hosts. Δgnt2 mutants had αalterations in cell wall properties related to terminal αor β-linked N-acetyl glucosamine. Mutant conidia and germlings also showed differences in structure and physicochemical surface properties. Conidial and hyphal aggregation differed between the mutant and wild type strains, in a pH independent manner. Transmission electron micrographs of germlings showed strong cell-to-cell adherence and the presence of an extracellular chemical matrix. Δgnt2 cell walls presented a significant reduction in N-linked oligosaccharides, suggesting the involvement of Gnt2 in N-glycosylation of cell wall proteins. Gnt2 was localized in Golgi-like sub-cellular compartments as determined by fluorescence microscopy of GFP::Gnt2 fusion protein after treatment with the antibiotic brefeldin A or by staining with fluorescent sphingolipid BODIPY-TR ceramide. Furthermore, density gradient ultracentrifugation allowed co-localization of GFP::Gnt2 fusion protein and Vps10p in subcellular fractions enriched in Golgi specific enzymatic activities. Our results suggest that N-acetylglucosaminyl transferases are key components for cell wall structure and influence interactions of F. oxysporum with both plant and animal hosts during pathogenicity.

  18. The Fusarium oxysporum gnt2, Encoding a Putative N-Acetylglucosamine Transferase, Is Involved in Cell Wall Architecture and Virulence

    Science.gov (United States)

    López-Fernández, Loida; Ruiz-Roldán, Carmen; Pareja-Jaime, Yolanda; Prieto, Alicia; Khraiwesh, Husam; Roncero, M. Isabel G.

    2013-01-01

    With the aim to decipher the molecular dialogue and cross talk between Fusarium oxysporum f.sp. lycopersci and its host during infection and to understand the molecular bases that govern fungal pathogenicity, we analysed genes presumably encoding N-acetylglucosaminyl transferases, involved in glycosylation of glycoproteins, glycolipids, proteoglycans or small molecule acceptors in other microorganisms. In silico analysis revealed the existence of seven putative N-glycosyl transferase encoding genes (named gnt) in F. oxysporum f.sp. lycopersici genome. gnt2 deletion mutants showed a dramatic reduction in virulence on both plant and animal hosts. Δgnt2 mutants had αalterations in cell wall properties related to terminal αor β-linked N-acetyl glucosamine. Mutant conidia and germlings also showed differences in structure and physicochemical surface properties. Conidial and hyphal aggregation differed between the mutant and wild type strains, in a pH independent manner. Transmission electron micrographs of germlings showed strong cell-to-cell adherence and the presence of an extracellular chemical matrix. Δgnt2 cell walls presented a significant reduction in N-linked oligosaccharides, suggesting the involvement of Gnt2 in N-glycosylation of cell wall proteins. Gnt2 was localized in Golgi-like sub-cellular compartments as determined by fluorescence microscopy of GFP::Gnt2 fusion protein after treatment with the antibiotic brefeldin A or by staining with fluorescent sphingolipid BODIPY-TR ceramide. Furthermore, density gradient ultracentrifugation allowed co-localization of GFP::Gnt2 fusion protein and Vps10p in subcellular fractions enriched in Golgi specific enzymatic activities. Our results suggest that N-acetylglucosaminyl transferases are key components for cell wall structure and influence interactions of F. oxysporum with both plant and animal hosts during pathogenicity. PMID:24416097

  19. The association of glutathione S-transferase GSTT1 and GSTM1 gene polymorphism with pseudoexfoliative glaucoma in a Pakistani population.

    NARCIS (Netherlands)

    Khan, M.I.; Micheal, S.; Akhtar, F.; Ahmed, W.; Ijaz, B.; Ahmed, A.; Qamar, R.

    2010-01-01

    PURPOSE: The aim of the present study was to investigate the association of glutathione S-transferase GSTT1 and GSTM1 genotypes with pseudoexfoliative glaucoma (PEXG) in a group of Pakistani patients. METHODS: Multiplex polymerase chain reaction was used to study the GSTT1 and GSTM1 polymorphisms in

  20. Les télécentres, centres de communications polyvalents | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    12 juil. 2011 ... ... la raison de leur absence et beaucoup répondent qu'ils ont eu une ... fournisseur de service Internet du télécentre, qui se trouve à Maputo ... Le télécentre s'est révélé être un fournisseur de services utile et recherché par les ...

  1. Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins.

    Science.gov (United States)

    Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

    2007-08-01

    INTRODUCTIONGlutathione-S-transferase (GST) fusion proteins have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis. This article describes the use of GST fusion proteins as probes for the identification of protein-protein interactions.

  2. Glutathione Transferase GSTπ In Breast Tumors Evaluated By Three Techniques

    Directory of Open Access Journals (Sweden)

    Rafael Molina

    1993-01-01

    Full Text Available The glutathione transferases are involved in intracellular detoxification reactions. One of these, GSTπ, is elevated in some breast cancer cells, particularly cells selected for resistance to anticancer agents. We evaluated GSTπ expression in 60 human breast tumors by three techniques, immunohistochemistry, Northern hybridization, and Western blot analysis. There was a significant positive correlation between the three methods, with complete concordance seen in 64% of the tumors. There was strong, inverse relationship between GSTπ expression and steroid receptor status with all of the techniques utili zed. [n addition, there was a trend toward higher GSTπ expression in poorly differentiated tumors, but no correlation was found between tumor GSTπ content and DNA ploidy or %S-phase. GSTπ expression was also detected in adjacent benign breast tissue as well as infiltrating lymphocytes; this expression may contribute to GSTπ measurements using either Northern hybridization or Western blot analysis. These re sults suggest that immunohistochemistry is the method of choice for measuring GSTπ in breast tumors.

  3. Isozyme-specific fluorescent inhibitor of glutathione s-transferase omega 1.

    Science.gov (United States)

    Son, Junghyun; Lee, Jae-Jung; Lee, Jun-Seok; Schüller, Andreas; Chang, Young-Tae

    2010-05-21

    Recently, the glutathione S-transferase omega 1 (GSTO1) is suspected to be involved in certain cancers and neurodegenerative diseases. However, profound investigation on the pathological roles of GSTO1 has been hampered by the lack of specific methods to determine or modulate its activity in biological systems containing other isoforms with similar catalytic function. Here, we report a fluorescent compound that is able to inhibit and monitor the activity of GSTO1. We screened 43 fluorescent chemicals and found a compound (6) that binds specifically to the active site of GSTO1. We observed that compound 6 inhibits GSTO1 by covalent modification but spares other isoforms in HEK293 cells and demonstrated that compound 6 could report the activity of GSTO1 in NIH/3T3 or HEK293 cells by measuring the fluorescence intensity of the labeled amount of GSTO1 in SDS-PAGE. Compound 6 is a useful tool to study GSTO1, applicable as a specific inhibitor and an activity reporter.

  4. Differential roles of tau class glutathione S-transferases in oxidative stress

    DEFF Research Database (Denmark)

    Kilili, Kimiti G; Atanassova, Neli; Vardanyan, Alla

    2004-01-01

    The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous...... Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress......-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery...

  5. Training centres - organization and management

    International Nuclear Information System (INIS)

    Kovar, P.

    1986-01-01

    In the lecture 'Training centres - organization and management' some principles and requirements which influence the organization, management and activity pattern of nuclear training centres, are briefly introduced. It is demonstrated, step by step, how these general principles are implemented in the development of the Czechoslovak nuclear power programme, it means, how the training of the NPP personnel proceeds in Czechoslovak nuclear training centres. General principles which are selected: a connection between the capacity of the training centre and the scope and needs of the nuclear power programme, a position of the training center within the institutional set-up, a structure and organization of the training system which complies with the system of NPP construction, reflect the pattern and the activity of the nuclear training centre and nuclear power technical level, a research group of workers in the nuclear training centre, main tasks and technical facilities, management of the training process and a transfer of knowledge and research results into the training process. The lecture is supplemented by pictures and slides. (orig.)

  6. Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

    International Nuclear Information System (INIS)

    LaCourse, E. James; Hernandez-Viadel, Mariluz; Jefferies, James R.; Svendsen, Claus; Spurgeon, David J.; Barrett, John; John Morgan, A.; Kille, Peter; Brophy, Peter M.

    2009-01-01

    The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

  7. Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

    Energy Technology Data Exchange (ETDEWEB)

    LaCourse, E. James, E-mail: james.la-course@liverpool.ac.u [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Hernandez-Viadel, Mariluz; Jefferies, James R. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Svendsen, Claus; Spurgeon, David J. [Centre for Ecology and Hydrology, Huntingdon PE28 2LS (United Kingdom); Barrett, John [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); John Morgan, A.; Kille, Peter [Biosciences, University of Cardiff, Cardiff CF10 3TL (United Kingdom); Brophy, Peter M. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom)

    2009-08-15

    The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

  8. Quantum Mechanical/Molecular Mechanical Free Energy Simulations of the Glutathione S-Transferase (M1-1) Reaction with Phenanthrene 9,10-Oxide

    NARCIS (Netherlands)

    Ridder, L.; Rietjens, I.M.C.M.; Vervoort, J.J.M.; Mulholland, A.J.

    2002-01-01

    Glutathione S-transferases (GSTs) play an important role in the detoxification of xenobiotics in mammals. They catalyze the conjugation of glutathione to a wide range of electrophilic compounds. Phenanthrene 9,10-oxide is a model substrate for GSTs, representing an important group of epoxide

  9. Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S -Transferases

    Energy Technology Data Exchange (ETDEWEB)

    Stoddard, Ethan G. [Chemical Biology and Exposure; Killinger, Bryan J. [Chemical Biology and Exposure; Nair, Reji N. [Chemical Biology and Exposure; Sadler, Natalie C. [Chemical Biology and Exposure; Volk, Regan F. [Chemical Biology and Exposure; Purvine, Samuel O. [Chemical Biology and Exposure; Shukla, Anil K. [Chemical Biology and Exposure; Smith, Jordan N. [Chemical Biology and Exposure; Wright, Aaron T. [Chemical Biology and Exposure

    2017-11-01

    Glutathione S-transferases (GSTs) comprise a highly diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione to various endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured by colorimetric assays, measurement of the individual contribution from specific isoforms and their contribution to the detoxification of xenobiotics in complex biological samples has not been possible. For this reason, we have developed two activity-based probes that characterize active glutathione transferases in mammalian tissues. The GST active site is comprised of a glutathione binding “G site” and a distinct substrate binding “H site”. Therefore, we developed (1) a glutathione-based photoaffinity probe (GSH-ABP) to target the “G site”, and (2) a probe designed to mimic a substrate molecule and show “H site” activity (GST-ABP). The GSH-ABP features a photoreactive moiety for UV-induced covalent binding to GSTs and glutathione-binding enzymes. The GST-ABP is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competitors in liver homogenates. Herein, we present robust tools for the novel characterization of enzyme- and active site-specific GST activity in mammalian model systems.

  10. Biochemical and Computational Analysis of the Substrate Specificities of Cfr and RlmN Methyltransferases

    DEFF Research Database (Denmark)

    Ntokou, Eleni; Hansen, Lykke Haastrup; Kongsted, Jacob

    2015-01-01

    -ray structure of RlmN. We used a trinucleotide as target sequence and assessed its positioning at the active site for methylation. The calculations are in accordance with different poses of the trinucleotide in the two enzymes indicating major evolutionary changes to shift the C2/C8 specificities. To explore......Cfr and RlmN methyltransferases both modify adenine 2503 in 23S rRNA (Escherichia coli numbering). RlmN methylates position C2 of adenine while Cfr methylates position C8, and to a lesser extent C2, conferring antibiotic resistance to peptidyl transferase inhibitors. Cfr and RlmN show high sequence...... interchangeability between Cfr and RlmN we constructed various combinations of their genes. The function of the mixed genes was investigated by RNA primer extension analysis to reveal methylation at 23S rRNA position A2503 and by MIC analysis to reveal antibiotic resistance. The catalytic site is expected...

  11. YgdE is the 2'-O-ribose methyltransferase RlmM specific for nucleotide C2498 in bacterial 23S rRNA

    DEFF Research Database (Denmark)

    Purta, Elzbieta; O'Connor, Michelle; Bujnicki, Janusz M

    2009-01-01

    The rRNAs of Escherichia coli contain four 2'-O-methylated nucleotides. Similar to other bacterial species and in contrast with Archaea and Eukaryota, the E. coli rRNA modifications are catalysed by specific methyltransferases that find their nucleotide targets without being guided by small...... complementary RNAs. We show here that the ygdE gene encodes the methyltransferase that catalyses 2'-O-methylation at nucleotide C2498 in the peptidyl transferase loop of E. coli 23S rRNA. Analyses of rRNAs using MALDI mass spectrometry showed that inactivation of the ygdE gene leads to loss of methylation...... at nucleotide C2498. The loss of ygdE function causes a slight reduction in bacterial fitness. Methylation at C2498 was restored by complementing the knock-out strain with a recombinant copy of ygdE. The recombinant YgdE methyltransferase modifies C2498 in naked 23S rRNA, but not in assembled 50S subunits...

  12. Acute cadmium intoxication induces alpha-class glutathione S-transferase protein synthesis and enzyme activity in rat liver

    International Nuclear Information System (INIS)

    Casalino, Elisabetta; Sblano, Cesare; Calzaretti, Giovanna; Landriscina, Clemente

    2006-01-01

    Acute cadmium intoxication affects glutathione S-transferase (GST) in rat liver. It has been found that 24 h after i.p. cadmium administration to rats, at a dose of 2.5 mg CdCl 2 kg -1 body weight, the activity of this enzyme in liver cytosol increased by 40%. A less stimulatory effect persisted till 48 h and thereafter the enzyme activity normalized. Since, GST isoenzymes belong to different classes in mammalian tissues, we used quantitative immunoassays to verify which family of GST isoenzymes is influenced by this intoxication. Only alpha-class glutathione S-transferase (α-GST) proteins were detected in rat liver cytosol and their level increased by about 25%, 24 h after cadmium treatment. No pi-GST isoforms were found in liver cytosol from either normal or cadmium-treated rats. Co-administration of actinomycin D with cadmium normalized both the protein level and the activity of α-GST, suggesting that some effect occurs on enzyme transcription of these isoenzymes by this metal. On the other hand, it seems unlikely that the stimulatory effect is due to the high level of peroxides caused by lipid peroxidation, since Vitamin E administration strongly reduced the TBARS level, but did not cause any GST activity decrease

  13. The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.

    Science.gov (United States)

    Gundogdu, Mehmet; Llabrés, Salomé; Gorelik, Andrii; Ferenbach, Andrew T; Zachariae, Ulrich; van Aalten, Daan M F

    2018-05-17

    O-linked β-N-acetyl- D -glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain. Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function. Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Call Centre- Computer Telephone Integration

    Directory of Open Access Journals (Sweden)

    Dražen Kovačević

    2012-10-01

    Full Text Available Call centre largely came into being as a result of consumerneeds converging with enabling technology- and by the companiesrecognising the revenue opportunities generated by meetingthose needs thereby increasing customer satisfaction. Regardlessof the specific application or activity of a Call centre, customersatisfaction with the interaction is critical to the revenuegenerated or protected by the Call centre. Physical(v, Call centreset up is a place that includes computer, telephone and supervisorstation. Call centre can be available 24 hours a day - whenthe customer wants to make a purchase, needs information, orsimply wishes to register a complaint.

  15. Addressing the challenges of patient-centred design

    Directory of Open Access Journals (Sweden)

    Karen LaBat

    2009-11-01

    Full Text Available Patient-centred design is a relatively new term, but a longstanding concept in clinical practice. This discussion looks at patient-centred design and explores the relationships of patient-centred design to universal design, user-centred design and the newer human-centred design. It also explores why interdisciplinary approaches are needed for patient-centred design and how interdisciplinary collaboration works to address the challenges of patient centred design. Successful patient-centred solutions can grow from collaborations which include shared visions, understanding of both the nature and degree of variation in the patient,materials, and the designed solution, clear regular communication among all parties with careful definition of terms, and respect for the inherent cultures of all disciplines involved.

  16. The Genetic Architecture of Murine Glutathione Transferases.

    Directory of Open Access Journals (Sweden)

    Lu Lu

    Full Text Available Glutathione S-transferase (GST genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6 and DBA2/J (D2--the BXD family--was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01 with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

  17. Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas

    DEFF Research Database (Denmark)

    Mandel, U; Hassan, H; Therkildsen, M H

    1999-01-01

    GalNAc-T1, -T2, and -T3. Application of this panel of novel antibodies revealed that GalNAc- transferases are differentially expressed in different cell lines, in spermatozoa, and in oral mucosa and carcinomas. For example, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, and Gal......NAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa. The expression patterns in normal oral mucosa were found to vary with cell differentiation, and for GalNAc-T2 and -T3 this was reflected in oral squamous cell carcinomas. The expression pattern of GalNAc-T1 was on the other hand changed...

  18. Neighbourhood Centres – Organisation, Management and Finance

    DEFF Research Database (Denmark)

    Larsen, Jacob Norvig

    to identify different financial models and analyse economic sustainability. As regards organisational and management models data were collected through documentary sources and by means of personal interviews and field visits to ten centres. Even within the analysed limited population of centres economic...... public subsidy. Some of the centres have high number of users on a daily basis, whereas others are only rarely used. It is explored how organisation, management and financial set-up differs among the centres. Quantitative data on financial issues and annual accounts of fifteen centres were analysed...... and institutional sustainability varies significantly. In organisational terms centres range from fully-integrated in the municipal administration to independent voluntary managed centres. In terms of financial, or economic, models variation is less pronounced as all centres to some degree are dependent on current...

  19. Energy centre microgrid model

    Energy Technology Data Exchange (ETDEWEB)

    Pasonen, R.

    2011-09-15

    A simulation model of Energy centre microgrid made with PSCAD simulation software version 4.2.1 has been built in SGEM Smart Grids and Energy Markets (SGEM) work package 6.6. Microgrid is an autonomous electric power system which can operate separate from common distribution system. The idea of energy centre microgrid concept was considered in Master of Science thesis 'Community Microgrid - A Building block of Finnish Smart Grid'. The name of energy centre microgrid comes from a fact that production and storage units are concentrated into a single location, an energy centre. This centre feeds the loads which can be households or industrial loads. Power direction flow on the demand side remains same compared to the current distribution system and allows to the use of standard fuse protection in the system. The model consists of photovoltaic solar array, battery unit, variable frequency boost converter, inverter, isolation transformer and demand side (load) model. The model is capable to automatically switch to islanded mode when there is a fault in outside grid and back to parallel operation mode when fault is removed. The modelled system responses well to load changes and total harmonic distortion related to 50Hz base frequency is kept under 1.5% while operating and feeding passive load. (orig.)

  20. RTEMS CENTRE- Support and Maintenance CENTRE to RTEMS Operating System

    Science.gov (United States)

    Silva, H.; Constantino, A.; Coutunho, M.; Freitas, D.; Faustino, S.; Mota, M.; Colaço, P.; Zulianello, M.

    2008-08-01

    RTEMS stands for Real-Time Operating System for Multiprocessor Systems. It is a full featured Real Time Operating System that supports a variety of open APIs and interface standards. It provides a high performance environment for embedded applications, including a fixed-priority preemptive/non-preemptive scheduler, a comprehensive set of multitasking operations and a large range of supported architectures. Support and maintenance CENTRE to RTEMS operating system (RTEMS CENTRE) is a joint initiative of ESA-Portugal Task force, aiming to build a strong technical competence in the space flight (on- board) software, to offer support, maintenance and improvements to RTEMS. This paper provides a high level description of the current and future activities of the RTEMS CENTRE. It presents a brief description of the RTEMS operating system, a description of the tools developed and distributed to the community [1] and the improvements to be made to the operating system, including facilitation for the qualification of RTEMS (4.8.0) [2] for the space missions.

  1. The peptidyl prolyl cis/trans isomerase Pin1/Ess1 inhibits phosphorylation and toxicity of tau in a yeast model for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ann De Vos

    2015-04-01

    Full Text Available Since hyperphosphorylation of protein tau is a crucial event in Alzheimer’s disease, additional mechanisms besides the interplay of kinase and phosphatase activities are investigated, such as the effect of the peptidyl prolyl cis/trans isomerase Pin1. This isomerase was shown to bind and isomerize phosphorylated protein tau, thereby restoring the microtubule associated protein function of tau as well as promoting the dephosphorylation of the protein by the trans-dependent phosphatase PP2A. In this study we used models based on Saccharomyces cerevisiae to further elucidate the influence of Pin1 and its yeast ortholog Ess1 on tau phosphorylation and self-assembly. We could demonstrate that in yeast, a lack of Pin1 isomerase activity leads to an increase in phosphorylation of tau at Thr231, comparable to AD brain and consistent with earlier findings in other model organisms. However, we could also distinguish an effect by Pin1 on other residues of tau, i.e. Ser235 and Ser198/199/202. Furthermore, depletion of Pin1 isomerase activity results in reduced growth of the yeast cells, which is enhanced upon expression of tau. This suggests that the accumulation of hyperphosphorylated and aggregation-prone tau causes cytotoxicity in yeast. This study introduces yeast as a valuable model organism to characterize in detail the effect of Pin1 on the biochemical characteristics of protein tau, more specifically its phosphorylation and aggregation.

  2. The relationship of glutathione-S-transferases copy number variation and indoor air pollution to symptoms and markers of respiratory disease

    DEFF Research Database (Denmark)

    Hersoug, Lars-Georg; Brasch-Andersen, Charlotte; Husemoen, Lise-Lotte

    2012-01-01

    Introduction: Exposure to particulate matter (PM) may induce inflammation and oxidative stress in the airways. Carriers of null polymorphisms of glutathione S-transferases (GSTs), which detoxify reactive oxygen species, may be particularly susceptible to the effects of PM. Objectives: To investig....... The relationship of glutathione-S-transferases copy number variation and indoor air pollution to symptoms and markers of respiratory disease. Clin Respir J 2011; DOI:10.1111/j.1752-699X.2011.00258.x.......: To investigate whether deletions of GSTM1 and GSTT1 modify the potential effects of exposure to indoor sources of PM on symptoms and objective markers of respiratory disease. Methods: We conducted a population-based, cross-sectional study of 3471 persons aged 18-69 years. Information about exposure to indoor......: We found that none of the symptoms and objective markers of respiratory disease were significantly associated with the GST null polymorphisms. An increasing number of positive alleles of the GSTM1 polymorphism tended to be associated lower prevalence of wheeze, cough, and high forced expiratory...

  3. The politics of patient-centred care.

    Science.gov (United States)

    Kreindler, Sara A

    2015-10-01

    Despite widespread belief in the importance of patient-centred care, it remains difficult to create a system in which all groups work together for the good of the patient. Part of the problem may be that the issue of patient-centred care itself can be used to prosecute intergroup conflict. This qualitative study of texts examined the presence and nature of intergroup language within the discourse on patient-centred care. A systematic SCOPUS and Google search identified 85 peer-reviewed and grey literature reports that engaged with the concept of patient-centred care. Discourse analysis, informed by the social identity approach, examined how writers defined and portrayed various groups. Managers, physicians and nurses all used the discourse of patient-centred care to imply that their own group was patient centred while other group(s) were not. Patient organizations tended to downplay or even deny the role of managers and providers in promoting patient centredness, and some used the concept to advocate for controversial health policies. Intergroup themes were even more obvious in the rhetoric of political groups across the ideological spectrum. In contrast to accounts that juxtaposed in-groups and out-groups, those from reportedly patient-centred organizations defined a 'mosaic' in-group that encompassed managers, providers and patients. The seemingly benign concept of patient-centred care can easily become a weapon on an intergroup battlefield. Understanding this dimension may help organizations resolve the intergroup tensions that prevent collective achievement of a patient-centred system. © 2013 John Wiley & Sons Ltd.

  4. Communications strategy for the Chernobyl Centre

    International Nuclear Information System (INIS)

    Kurilchik, Mykola; Green, Len

    2000-01-01

    This Communications Strategy was developed for the International Chernobyl Centre (ICC) as part of a joint UK/Ukraine project, sponsored by the Department of Trade and Industry and NNC Limited. The Plan was developed during four weeks of workshop discussions in the UK between staff from the centre and experienced PR Professionals from NNC Limited. The requirements for a sustained communications activity at the ICC go much further than simply enhancing or promoting the Centre's scientific and technical activities. Raising sufficient awareness of the Centre among potential funding agents and commercial partners is critical to its future development as a major centre for international co-operation and research. It is only through establishing and developing effective communications that the Centre will become well enough known and understood both within the Ukraine, and internationally, to secure its long term future. However, as the workshop programme unfolded, it also became clear that communications was in itself a legitimate and necessary function of the Centre, and part of the foundations of its existence. The Centre has a fundamental role as an 'information exchange', collecting and communicating information from within the Ukraine to the rest of the world, and interpreting world interest and attitudes to the Ukraine Government and nuclear industry. As such compliments the efforts of individual power plant and corporate PR functions within the Ukraine nuclear energy sector

  5. Discussion on 'Centres of excellence' in Africa

    International Nuclear Information System (INIS)

    Riad, S.

    1999-01-01

    In Africa, Centres of Excellence should be oriented to build up scientific and technological capacity in the four topics of international Monitoring System related technologies, namely, seismic monitoring, hydro acoustic monitoring, infrasound monitoring and radionuclides monitoring. Training programs on these topics should be a major objective. A network of such centres should be established in a number of African countries. Centres should be equipped with means and materials for on-line course dispatch to interested training centres or research institutions. African centres should develop strong relationship among themselves through information and data exchange and sharing, harmonization of training programs. National data centres may be established as a component of the African Centre of Excellence. States Signatories may authorize the establishment of a specific fund to support the activities of the African center

  6. The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

    LENUS (Irish Health Repository)

    Flanagan, J M

    2010-02-01

    Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

  7. The Aube centre

    International Nuclear Information System (INIS)

    1996-07-01

    This educational booklet is devoted to a general presentation of the Aube radioactive wastes storage centre. After a short presentation of the Andra, the French national agency for the management of radioactive wastes, it gives some general information about radioactive wastes (origin, classification), containers (quality assurance and different types), wastes transportation (planning, safety), and about the Aube centre itself: description, treatment and conditioning of drums (compacting and injection), storage facilities, geological situation of the site, and environmental controls. (J.S.)

  8. Glutathione S-transferase gene polymorphisms in presbycusis.

    Science.gov (United States)

    Ateş, Nurcan Aras; Unal, Murat; Tamer, Lülüfer; Derici, Ebru; Karakaş, Sevim; Ercan, Bahadir; Pata, Yavuz Selim; Akbaş, Yücel; Vayisoğlu, Yusuf; Camdeviren, Handan

    2005-05-01

    Glutathione and glutathione-related antioxidant enzymes are involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species. Reactive oxygen species generation occurs in prolonged relative hypoperfusion conditions such as in aging. The etiology of presbycusis is much less certain; however, a complex genetic cause is most likely. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of (glutathione S-transferase (GST) M1, T1 and P1 genotypes may be associated with the risk of age-related hearing loss. We examined 68 adults with presbycusis and 69 healthy controls. DNA was extracted from whole blood, and the GSTM1, GSTT1 and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. Gene polymorphisms at GSTM1, GSTT1, and GSTP1 in subjects with presbycusis were not significantly different than in the controls (p > 0.05). Also, the combinations of different GSTM1, GSTT1, and GSTP1 genotypes were not an increased risk of presbycusis (p > 0.05). We could not demonstrate any significant association between the GSTM1, GSTT1, and GSTP1 polymorphism and age-related hearing loss in this population. This may be because of our sample size, and further studies need to investigate the exact role of GST gene polymorphisms in the etiopathogenesis of the presbycusis.

  9. Glutathione S-Transferase of Brown Planthoppers (Nilaparvata lugens) Is Essential for Their Adaptation to Gramine-Containing Host Plants

    OpenAIRE

    Sun, Xiao-Qin; Zhang, Mao-Xin; Yu, Jing-Ya; Jin, Yu; Ling, Bing; Du, Jin-Ping; Li, Gui-Hua; Qin, Qing-Ming; Cai, Qing-Nian

    2013-01-01

    Plants have evolved complex processes to ward off attacks by insects. In parallel, insects have evolved mechanisms to thwart these plant defenses. To gain insight into mechanisms that mediate this arms race between plants and herbivorous insects, we investigated the interactions between gramine, a toxin synthesized by plants of the family Gramineae, and glutathione S transferase (GST), an enzyme found in insects that is known to detoxify xenobiotics. Here, we demonstrate that rice (Oryza sati...

  10. Glutathione transferases are structural and functional outliers in the thioredoxin fold.

    Science.gov (United States)

    Atkinson, Holly J; Babbitt, Patricia C

    2009-11-24

    Glutathione transferases (GSTs) are ubiquitous scavengers of toxic compounds that fall, structurally and functionally, within the thioredoxin fold suprafamily. The fundamental catalytic capability of GSTs is catalysis of the nucleophilic addition or substitution of glutathione at electrophilic centers in a wide range of small electrophilic compounds. While specific GSTs have been studied in detail, little else is known about the structural and functional relationships between different groupings of GSTs. Through a global analysis of sequence and structural similarity, it was determined that variation in the binding of glutathione between the two major subgroups of cytosolic (soluble) GSTs results in a different mode of glutathione activation. Additionally, the convergent features of glutathione binding between cytosolic GSTs and mitochondrial GST kappa are described. The identification of these structural and functional themes helps to illuminate some of the fundamental contributions of the thioredoxin fold to catalysis in the GSTs and clarify how the thioredoxin fold can be modified to enable new functions.

  11. Centre for urban ecotechnology in ``Oeksnehallen``

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    The Lord Mayor`s Department of the municipality of Copenhagen, Denmark, has with support from this project made a proposal for the establishment of the Centre for Urban Ecotechnology in ``Oeksnehallen``, located in the Vesterbro area of the city. The centre should contribute to the dissemination of knowledge on ecological techniques (regarding passive solar energy etc.) to the inhabitants of Vesterbro and other citizens of Copenhagen, and also serve as a centre in an European context. The ecological demonstration centre will cover an area of two thousand square meters and will also include a cafe, a room for showing coloured slides, facilities for exhibitions created by the center and interested firms etc. The centre should play an important role as part of the ecological concept of urban renewal in Vesterbro. (author).

  12. Netherlands Reactor Centre

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Briefly reviews the last year's work of the twenty year old Netherlands Reactor Centre (RCN) in the fields of reactor safety, fissile material, nuclear fission, non-nuclear energy systems and overseas co-operation. The annual report thus summarised is the last one to appear under the name of RCN. The terms of reference of the organisation having been broadened to include research into energy supply in general, it is to be known in future as the Netherlands Energy Research Centre (ECN). (D.J.B.)

  13. Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example.

    Science.gov (United States)

    Xie, Yiyue; Dahlin, Jayme L; Oakley, Aaron J; Casarotto, Marco G; Board, Philip G; Baell, Jonathan B

    2018-05-10

    Early stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme glutathione transferase omega-1 (GSTO1-1) as an example of a relatively difficult target and review the associated literature involving small-molecule inhibitors. As part of this process we deliberately pay closer-than-usual attention to assay interference and hit quality aspects. We believe this Perspective will be a useful guide for future development of GSTO1-1 inhibitors, as well serving as a template for future review formats of new or difficult targets.

  14. Fuel cycle centres

    International Nuclear Information System (INIS)

    Hagen, M.

    1977-01-01

    The concept of co-locating and integrating fuel cycle facilities at one site is discussed. This concept offers considerable advantages, especially in minimizing the amount of radioactive material to be transported on public roads. Safeguards and physical protection as relating to such an integrated system of facilities are analysed in detail, also industrial and commercial questions. An overall risk-benefit evaluation turns out to be in favour of fuel cycle centres. These centres seem to be specifically attractive with regard to the back end of the fuel cycle, including on-site disposal of radioactive wastes. The respective German approach is presented as an example. Special emphasis is given to the site selection procedures in this case. Time scale and cost for the implementation of this concept are important factors to be looked at. Since participation of governmental institutions in these centres seems to be indispensable their respective roles as compared to industry must be clearly defined. The idea of adjusting fuel cycle centres to regional rather than national use might be an attractive option, depending on the specific parameters in the region, though results of existing multinational ventures are inconclusive in this respect. Major difficulties might be expected e.g. because of different national safety regulations and standards as well as commercial conditions among partner countries. Public acceptance in the host country seems to be another stumbling block for the realization of this type of multinational facilities

  15. Preparation of emergency care centre exercises

    International Nuclear Information System (INIS)

    Schnadt, H.; Miska, H.

    2011-01-01

    Setup and operation of emergency care centres (sometimes also addressed as emergency reception centres) are part of emergency response in the environs of nuclear power plants. The preparation of an exercise scenario for such a centre is very demanding on the responsible agency. Therefore, a computer code has been developed which helps to translate the exercise objectives into instructions for figurants which simulate the affected population. These instructions are intended to steer a determined flow of people through the emergency care centre by providing fictitious radiological readings and by injecting the demand for additional actions of response personnel by statements and questions. (orig.)

  16. The activity of glutathione S-transferase in hepatopancreas of Procambarus clarkii: seasonal variations and the influence of environmental pollutants.

    Science.gov (United States)

    Nies, E; Almar, M M; Hermenegildo, C; Monsalve, E; Romero, F J

    1991-01-01

    1. The glutathione S-transferase activity in hepatopancreas of the American red crayfish Procambarus clarkii after 15 days' acclimatization in tap water aquaria was measured in specimens collected monthly for a whole year, and shows seasonal variation. 2. Previous data on the environmental pollution of Lake Albufera suggest a possible correlation with the activity tested in the different seasons of the year considering the results of non-acclimatized animals.

  17. Contribution of liver mitochondrial membrane-bound glutathione transferase to mitochondrial permeability transition pores

    International Nuclear Information System (INIS)

    Hossain, Quazi Sohel; Ulziikhishig, Enkhbaatar; Lee, Kang Kwang; Yamamoto, Hideyuki; Aniya, Yoko

    2009-01-01

    We recently reported that the glutathione transferase in rat liver mitochondrial membranes (mtMGST1) is activated by S-glutathionylation and the activated mtMGST1 contributes to the mitochondrial permeability transition (MPT) pore and cytochrome c release from mitochondria [Lee, K.K., Shimoji, M., Quazi, S.H., Sunakawa, H., Aniya, Y., 2008. Novel function of glutathione transferase in rat liver mitochondrial membrane: role for cytochrome c release from mitochondria. Toxcol. Appl. Pharmacol. 232, 109-118]. In the present study we investigated the effect of reactive oxygen species (ROS), generator gallic acid (GA) and GST inhibitors on mtMGST1 and the MPT. When rat liver mitochondria were incubated with GA, mtMGST1 activity was increased to about 3 fold and the increase was inhibited with antioxidant enzymes and singlet oxygen quenchers including 1,4-diazabicyclo [2,2,2] octane (DABCO). GA-mediated mtMGST1 activation was prevented by GST inhibitors such as tannic acid, hematin, and cibacron blue and also by cyclosporin A (CsA). In addition, GA induced the mitochondrial swelling which was also inhibited by GST inhibitors, but not by MPT inhibitors CsA, ADP, and bongkrekic acid. GA also released cytochrome c from the mitochondria which was inhibited completely by DABCO, moderately by GST inhibitors, and somewhat by CsA. Ca 2+ -mediated mitochondrial swelling and cytochrome c release were inhibited by MPT inhibitors but not by GST inhibitors. When the outer mitochondrial membrane was isolated after treatment of mitochondria with GA, mtMGST1 activity was markedly increased and oligomer/aggregate of mtMGST1 was observed. These results indicate that mtMGST1 in the outer mitochondrial membrane is activated by GA through thiol oxidation leading to protein oligomerization/aggregation, which may contribute to the formation of ROS-mediated, CsA-insensitive MPT pore, suggesting a novel mechanism for regulation of the MPT by mtMGST1

  18. Council celebrates CERN Control Centre

    CERN Multimedia

    2006-01-01

    With the unveiling of its new sign, the CERN Control Centre was officially inaugurated on Thursday 16 March. To celebrate its startup, CERN Council members visited the sleek centre, a futuristic-looking room filled with a multitude of monitoring screens.

  19. The Juxtaposition of Ribose Hydroxyl Groups: The Root of Biological Catalysis and the RNA World?

    Science.gov (United States)

    Bernhardt, Harold S.

    2015-06-01

    We normally think of enzymes as being proteins; however, the RNA world hypothesis suggests that the earliest biological catalysts may have been composed of RNA. One of the oldest surviving RNA enzymes we are aware of is the peptidyl transferase centre (PTC) of the large ribosomal RNA, which joins amino acids together to form proteins. Recent evidence indicates that the enzymatic activity of the PTC is principally due to ribose 2 '-OHs. Many other reactions catalyzed by RNA and/or in which RNA is a substrate similarly utilize ribose 2 '-OHs, including phosphoryl transfer reactions that involve the cleavage and/or ligation of the ribose-phosphate backbone. It has recently been proposed by Yakhnin (2013) that phosphoryl transfer reactions were important in the prebiotic chemical evolution of RNA, by enabling macromolecules composed of polyols joined by phosphodiester linkages to undergo recombination reactions, with the reaction energy supplied by the phosphodiester bond itself. The almost unique juxtaposition of the ribose 2'-hydroxyl and 3'-oxygen in ribose-containing polymers such as RNA, which gives ribose the ability to catalyze such reactions, may have been an important factor in the selection of ribose as a component of the first biopolymer. In addition, the juxtaposition of hydroxyl groups in free ribose: (i) allows coordination of borate ions, which could have provided significant and preferential stabilization of ribose in a prebiotic environment; and (ii) enhances the rate of permeation by ribose into a variety of lipid membrane systems, possibly favouring its incorporation into early metabolic pathways and an ancestral ribose-phosphate polymer. Somewhat more speculatively, hydrogen bonds formed by juxtaposed ribose hydroxyl groups may have stabilized an ancestral ribose-phosphate polymer against degradation (Bernhardt and Sandwick 2014). I propose that the almost unique juxtaposition of ribose hydroxyl groups constitutes the root of both biological

  20. The Australian centre for RF bioeffects research (ACRBR) - an NHMRC centre of research excellence

    International Nuclear Information System (INIS)

    Wood, A.; Croft, R.; Abramson, M.; Anderson, V.; Cosic, I.; Finnie, J.; McKenzie, R.

    2004-01-01

    Full text: The Australian Centre for Radiofrequency Bioeffects Research (ACRBR) is a newly established multi-institutional research centre which seeks to research questions pertaining to possible health effects of exposure to radiofrequency devices, such as mobile phones and which is funded under the Australian National Health and Medical Research Council (NHMRC) Centres of Research Excellence funding program. The Centre of Research Excellence in Electromagnetic Energy is combining the efforts of engineers, epidemiologists, physicists, psychophysiologists and veterinary pathologists from RMIT University, the Institute of Medical and Veterinary Science in South Australia (IMVS), Monash University, Swinburne University of Technology and Telstra Research Laboratories (TRL). The centre is funded at $2.5 M over five years and will undertake a program of research to address the issue of exposure to radiofrequency (RF) devices and health. It will also train new scientists, keep the community informed of ongoing developments and help the development of government policies in this area of considerable public concern. The 5-year program has the following components: Neurobiology: One important area where there is a perceived research gap is in the area of potential neurological effects, which will hence be a major focus of this Centre. The proposed studies range from in vitro and in vivo research studies of RF effects on neuron and neural system functioning in rodents, to that of RF effects on simple neural function, cognition and subjective report in humans. The latter series of studies have been developed to account for the consensus view that more emphasis needs to be placed on possible differences in RF population sensitivity (e.g. youth versus aged, and ' electromagnetic hypersensitives'). Epidemiological studies are an important tool in studying the impact on public health from exposure of whole populations to modern radio technologies. Cancer outcomes in this area of

  1. Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase.

    Science.gov (United States)

    Bergstrand, H; Eriksson, T; Hallberg, A; Johansson, B; Karabelas, K; Michelsen, P; Nybom, A

    1992-12-01

    To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Training centres in Latin America

    International Nuclear Information System (INIS)

    1959-01-01

    Early 1958 the Brazilian representative on the Board of Governors of the International Atomic Energy Agency - supported by the Governors from Argentina and Guatemala -proposed that a study should be made of the possibility of setting up one or more atomic energy training centres in Latin America. On the Board's recommendation, the Director General of the Agency appointed a fact-finding team to make anon-the-spot study. In drafting this report the team was invited to consider the following points: (a) The need for establishing one or more regional training centres; (b) Existing facilities that are being or could be used for training, together with technical data concerning them; (c) The general scientific technological and industrial conditions of the countries visited insofar as they have a bearing on their training needs and capabilities. The authors of the report conclude that 'a training centre in radio-botany should provide vitally needed knowledge and vitally needed specialists to all the agricultural installations in Latin America. A training centre like this might provide an excellent model upon which to base training centres in other areas'. The report recommends that: 1. The Agency should meet the requests of Latin American universities by, for example, supplying equipment and sending experts; 2. At least one specialized training centre should be established as soon as possible. Taking as an example the field of radio-botany, such a centre would provide trained specialists in radio-botany to agricultural institutions throughout Latin America and also provide basic research results vital to agriculture. The cost of new facilities might be of the order of $7 500 000, with an annual budget of approximately $650 000. Staff required: 40 scientists and 175 employees; 3. Whenever it appears feasible to gather necessary staff of high creative ability and established productivity and when funds can be made available for facilities, equipment and operating costs, at

  3. Training centres in Latin America

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1959-04-15

    Early 1958 the Brazilian representative on the Board of Governors of the International Atomic Energy Agency - supported by the Governors from Argentina and Guatemala -proposed that a study should be made of the possibility of setting up one or more atomic energy training centres in Latin America. On the Board's recommendation, the Director General of the Agency appointed a fact-finding team to make anon-the-spot study. In drafting this report the team was invited to consider the following points: (a) The need for establishing one or more regional training centres; (b) Existing facilities that are being or could be used for training, together with technical data concerning them; (c) The general scientific technological and industrial conditions of the countries visited insofar as they have a bearing on their training needs and capabilities. The authors of the report conclude that 'a training centre in radio-botany should provide vitally needed knowledge and vitally needed specialists to all the agricultural installations in Latin America. A training centre like this might provide an excellent model upon which to base training centres in other areas'. The report recommends that: 1. The Agency should meet the requests of Latin American universities by, for example, supplying equipment and sending experts; 2. At least one specialized training centre should be established as soon as possible. Taking as an example the field of radio-botany, such a centre would provide trained specialists in radio-botany to agricultural institutions throughout Latin America and also provide basic research results vital to agriculture. The cost of new facilities might be of the order of $7 500 000, with an annual budget of approximately $650 000. Staff required: 40 scientists and 175 employees; 3. Whenever it appears feasible to gather necessary staff of high creative ability and established productivity and when funds can be made available for facilities, equipment and operating costs, at

  4. The EGF repeat-specific O-GlcNAc-transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila.

    Directory of Open Access Journals (Sweden)

    Reto Müller

    Full Text Available The O-GlcNAc transferase Eogt modifies EGF repeats in proteins that transit the secretory pathway, including Dumpy and Notch. In this paper, we show that the Notch ligands Delta and Serrate are also substrates of Eogt, that mutation of a putative UDP-GlcNAc binding DXD motif greatly reduces enzyme activity, and that Eogt and the cytoplasmic O-GlcNAc transferase Ogt have distinct substrates in Drosophila larvae. Loss of Eogt is larval lethal and disrupts Dumpy functions, but does not obviously perturb Notch signaling. To identify novel genetic interactions with eogt, we investigated dominant modification of wing blister formation caused by knock-down of eogt. Unexpectedly, heterozygosity for several members of the canonical Notch signaling pathway suppressed wing blister formation. And importantly, extensive genetic interactions with mutants in pyrimidine metabolism were identified. Removal of pyrimidine synthesis alleles suppressed wing blister formation, while removal of uracil catabolism alleles was synthetic lethal with eogt knock-down. Therefore, Eogt may regulate protein functions by O-GlcNAc modification of their EGF repeats, and cellular metabolism by affecting pyrimidine synthesis and catabolism. We propose that eogt knock-down in the wing leads to metabolic and signaling perturbations that increase cytosolic uracil levels, thereby causing wing blister formation.

  5. The Centres for Environment-friendly Energy Research (FME)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    High expectations for Norway's Centres for Environment-friendly Energy Research (FME).The FME centres address a broad range of areas, allcentral to developing the energy sector of the future. The activities of the eight centres established in 2009 focus on renewable energy, raising energy efficiency, energy planning, and carbon capture and storage (CCS). In 2011 three new FME centres were established which focus on social science-related energy research. The FME scheme is a direct follow-up of the broad-based political agreement on climate policy achieved in the Storting in January 2008, and of the national RandD Energi21 strategy submitted in February 2008 to the Ministry of Petroleum and Energy. In April 2008 the Research Council of Norway's Executive Board decided to launch a process to establish centres for environment-friendly energy research, and a funding announcement was issued that same year. In 2010 it was decided that additional FME centres would be established in the field of social science-related energy research. After a thorough assessment of each project (based on feasibility, scientific merit, potential to generate value creation and innovation, and composition of the consortium) eight applicants were selected to become FME centres in February 2009. A new call for proposals was issued in 2010, and three more centres were awarded FME status in February 2011. The objective of the FME scheme is to establish time-limited research centres which conduct concentrated, focused and long-term research of high international calibre in order to solve specific challenges in the energy sphere. The selected centres must exhibit higher goals, a longer-term perspective and a more concentrated focus than is required under other funding instruments for the same scientific area. The make-up of the centres is critical to achieving this objective. The centres bring together Norway's leading research institutions and key players in private enterprise, the

  6. A chloroplast-localized and auxin-induced glutathione S-transferase from phreatophyte Prosopis juliflora confer drought tolerance on tobacco.

    Science.gov (United States)

    George, Suja; Venkataraman, Gayatri; Parida, Ajay

    2010-03-01

    Plant growth and productivity are adversely affected by various abiotic stress factors. In our previous study, we used Prosopis juliflora, a drought-tolerant tree species of Fabaceae, as a model plant system for mining genes functioning in abiotic stress tolerance. Large-scale random EST sequencing from a cDNA library obtained from drought-stressed leaves of 2-month-old P. juliflora plants resulted in identification of three different auxin-inducible glutathione S-transferases. In this paper, we report the cellular localization and the ability to confer drought tolerance in transgenic tobacco of one of these GSTs (PjGSTU1). PjGSTU1 was overexpressed in Escherichia coli and GST and GPX activities in total protein samples were assayed and compared with controls. The results indicated that PjGSTU1 protein forms a functional homo-dimer in recombinant bacteria with glutathione transferase as well as glutathione peroxidase activities. PjGSTU1 transgenic tobacco lines survived better under conditions of 15% PEG stress compared with control un-transformed plants. In vivo localization studies for PjGSTU1 using GFP fusion revealed protein localization in chloroplasts of transgenic plants. The peroxidase activity of PjGSTU1 and its localization in the chloroplast indicates a possible role for PjGSTU1 in ROS removal. Copyright 2009 Elsevier GmbH. All rights reserved.

  7. Glutathione transferase-mediated benzimidazole-resistance in Fusarium graminearum.

    Science.gov (United States)

    Sevastos, A; Labrou, N E; Flouri, F; Malandrakis, A

    2017-09-01

    Fusarium graminearum laboratory mutants moderately (MR) and highly (HR) benzimidazole-resistant, carrying or not target-site mutations at the β 2 -tubulin gene were utilized in an attempt to elucidate the biochemical mechanism(s) underlying the unique BZM-resistance paradigm of this fungal plant pathogen. Relative expression analysis in the presence or absence of carbendazim (methyl-2-benzimidazole carbamate) using a quantitative Real Time qPCR (RT-qPCR) revealed differences between resistant and the wild-type parental strain although no differences in expression levels of either β 1 - or β 2 -tubulin homologue genes were able to fully account for two of the highly resistant phenotypes. Glutathione transferase (GST)-mediated detoxification was shown to be -at least partly- responsible for the elevated resistance levels of a HR isolate bearing the β 2 -tubulin Phe200Tyr resistance mutation compared with another MR isolate carrying the same mutation. This benzimidazole-resistance mechanism is reported for the first time in F. graminearum. No indications of detoxification involved in benzimidazole resistance were found for the rest of the isolates as revealed by GST and glutathione peroxidase (GPx) activities and bioassays using monoxygenase and hydrolase detoxification enzyme inhibiting synergists. Interestingly, besides the Phe200Tyr mutation-carrying HR isolate, the remaining highly-carbendazim resistant phenotypes could not be associated with any of the target site modification/overproduction, detoxification or reduced uptake-increased efflux mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The centre of mass of a triangular plate

    International Nuclear Information System (INIS)

    Sluesarenko, Viktor; Rojas, Roberto; Fuster, Gonzalo

    2008-01-01

    We present a derivation for the coordinates of the centre of mass-or centre of gravity-of a homogeneous triangular plate by using scaling and symmetry. We scale the triangular plate by a factor of 2 and divide its area into four plates identical to the original. By symmetry, we assert that the centre of mass of two identical masses lies at the midpoint of the line joining their centres of mass. By relating the centres of mass of the original to those of the scaled plates, we find the coordinates of the centre of mass as the solution of an algebraic equation

  9. The Bruce Energy Centre

    International Nuclear Information System (INIS)

    Jones, R.I.

    1982-06-01

    The Bruce Energy Centre Development Corporation is a joint venture of the Ontario Energy Corporation and 6 private companies formed to market surplus steam from the Bruce Nuclear Power Development. The corporation will also sell or lease land near Bruce NPD. The Bruce Energy Centre has an energy output of 900 BTU per day per dollar invested. Potential customers include greenhouse operators, aquaculturalists, food and beverage manufacturers, and traditional manufacturers

  10. Visits to Tier-1 Computing Centres

    CERN Multimedia

    Dario Barberis

    At the beginning of 2007 it became clear that an enhanced level of communication is needed between the ATLAS computing organisation and the Tier-1 centres. Most usual meetings are ATLAS-centric and cannot address the issues of each Tier-1; therefore we decided to organise a series of visits to the Tier-1 centres and focus on site issues. For us, ATLAS computing management, it is most useful to realize how each Tier-1 centre is organised, and its relation to the associated Tier-2s; indeed their presence at these visits is also very useful. We hope it is also useful for sites... at least, we are told so! The usual participation includes, from the ATLAS side: computing management, operations, data placement, resources, accounting and database deployment coordinators; and from the Tier-1 side: computer centre management, system managers, Grid infrastructure people, network, storage and database experts, local ATLAS liaison people and representatives of the associated Tier-2s. Visiting Tier-1 centres (1-4). ...

  11. Patient-centred outcomes research: perspectives of patient stakeholders.

    Science.gov (United States)

    Chhatre, Sumedha; Gallo, Joseph J; Wittink, Marsha; Schwartz, J Sanford; Jayadevappa, Ravishankar

    2017-11-01

    To elicit patient stakeholders' experience and perspectives about patient-centred care. Qualitative. A large urban healthcare system. Four patient stakeholders who are prostate cancer survivors. Experience and perspectives of patient stakeholders regarding patient-centred care and treatment decisions. Our patient stakeholders represented a diverse socio-demographic group. The patient stakeholders identified engagement and dialogue with physicians as crucial elements of patient-centred care model. The degree of patient-centred care was observed to be dependent on the situations. High severity conditions warranted a higher level of patient involvement, compared to mild conditions. They agreed that patient-centred care should not mean that patients can demand inappropriate treatments. An important attribute of patient-centred outcomes research model is the involvement of stakeholders. However, we have limited knowledge about the experience of patient stakeholders in patient-centred outcomes research. Our study indicates that patient stakeholders offer a unique perspective as researchers and policy-makers aim to precisely define patient-centred research and care.

  12. Smart work centres in rural areas

    DEFF Research Database (Denmark)

    Lorentzen, Anne Birte

    This paper discusses the establishment of telework centres as an element in local development strategies in rural areas, with a particular view to two new telework centres in region North Denmark. The paper argues that telework centres do not represent an easy solution to problems of local...... development and environmental sustainability, and further, that technology may not even be the most important feature needed to make them function as such....

  13. Glycoproteins and sialyl transferase of human B lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Lui, S.W.L.; Ng, M.H.

    1980-01-01

    We used two radiolabeling methods to study glycoproteins on the surface of lymphoblastoid cells. One of the methods affects tritiation of residues which are oxidized with galactose oxidase and the other causes tritiation of neuraminic acid residues. This approach was shown to allow a better resolution of cell surface glycoproteins than if either method were used alone. Glycoproteins of B 1 - 19 cells which harbor the Epstein-Barr virus genomes were compared with those of its parental cell line, BJAB, which does not harbor the viral genomes. These studies did not reveal a unique viral protein. A 28,000 mol. wt. glycoprotein was found to be the most prominent neuraminic acidlabeled product of B 1 - 19 cells and also of the two other cell lines, Raji and Ly38, which harbor the EBV genomes. A similar molecular weight species from BJAB cells identified by galactose oxidase labeling might be deficient in neuraminic acid residues as it was poorly labeled by the periodate oxidation method. The neuraminic acid content and level of sialyl transferase of BJAB cells were found to be lower than those of the other cell lines studied. (auth.)

  14. Echinococcus granulosus: Evidence of a heterodimeric glutathione transferase built up by phylogenetically distant subunits.

    Science.gov (United States)

    Arbildi, Paula; La-Rocca, Silvana; Lopez, Veronica; Da-Costa, Natalia; Fernandez, Veronica

    2017-01-01

    In the cestode parasite Echinococcus granulosus, three phylogenetically distant cytosolic glutathione transferases (GSTs) (EgGST1, 2 and 3) were identified. Interestingly, the C-terminal domains of EgGST3 and EgGST2 but not EgGST1, exhibit all amino acids involved in Sigma-class GST dimerization. Here, we provide evidence indicating that EgGST2 and EgGST3 naturally form a heterodimeric structure (EgGST2-3), and also we report the enzymatic activity of the recombinant heterodimer. EgGST2-3 might display novel properties able to influence the infection establishment. This is the first report of a stable heterodimeric GST built up by phylogenetically distant subunits. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. The ideal Atomic Centre

    International Nuclear Information System (INIS)

    Mas, R.

    1965-01-01

    The author presents considerations which should prove to be of interest to all those who have to design, to construct and to operate a nuclear research centre. A large number of the ideas presented can also be applied to non-nuclear scientific research centres. In his report the author reviews: various problems with which the constructor is faced: ground-plan, infrastructure, buildings and the large units of scientific equipment in the centre, and those problems facing the director: maintenance, production, supplies, security. The author stresses the relationship which ought to exist between the research workers and the management. With this aim in view he proposes the creation of National School for Administration in Research which would train administrative executives for public or private organisations; they would be specialised in the fields of fundamental or applied research. (author) [fr

  16. CENTRE FOR GEOMETRICAL METROLOGY

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    The objective of this Annual Report is to give a general introduction to CGM as well as to give an account of the tasks carried out using the facilities of CGM's Instrument Centre during 1998 and 1999.......The objective of this Annual Report is to give a general introduction to CGM as well as to give an account of the tasks carried out using the facilities of CGM's Instrument Centre during 1998 and 1999....

  17. The "magic" of tutorial centres in Hong Kong: An analysis of media marketing and pedagogy in a tutorial centre

    Science.gov (United States)

    Koh, Aaron

    2014-12-01

    Why do more than three-quarters of Hong Kong's senior secondary students flock to tutorial centres like moths to light? What is the "magic" that is driving the popularity of the tutorial centre enterprise? Indeed, looking at the ongoing boom of tutorial centres in Hong Kong (there are almost 1,000 of them), it is difficult not to ask these questions. This paper examines the phenomenon of tutorial centres in Hong Kong and seeks to understand what draws students to these centres. Combining theories of marketing semiotics and emotion studies, the author investigates the pivotal role of media marketing in generating the "magic" of tutorial centres, whose advertising strategy includes, for example, a display of billboard posters featuring stylishly-dressed "celebrity teachers". The author reviews some of the literature available on the subject of tutorial centres. In a case study approach, he then maps out the pedagogy he observed in an English tutorial class, seeking heuristic insights into the kind of teaching students in the study were looking for. He argues that part of the "magical" attraction of what are essentially "cram schools" is their formulaic pedagogy of teaching and reinforcing exam skills. Finally, the paper considers the social implications of the tutorial centre industry in terms of media marketing of education and unequal access to tutorial services.

  18. Norway's centres for environment-friendly energy research (CEERs)

    Energy Technology Data Exchange (ETDEWEB)

    2009-07-01

    In February 2009 Norway's Minister of Petroleum and Energy announced the establishment of eight new Centres for Environment-friendly Energy Research (CEERs). The centres form national teams within the areas of offshore wind energy, solar energy, energy efficiency, bio energy, energy planning and design, and carbon capture and storage. These centres are: BIGCCS Centre - International CCS Research Centre; Centre for Environmental Design of Renewable Energy (CEDREN); Bioenergy Innovation Centre (CenBio); Norwegian Centre for Offshore Wind Energy (NORCOW E); Norwegian Research Centre for Offshore Wind Technology (NOWITECH); The Norwegian Research Centre for Solar Cell Technology; SUbsurface CO{sub 2} storage - Critical Elements and Superior Strategy (SUCCESS) The Research Centre on Zero Emission Buildings - ZEB (AG)

  19. Introducing the PET Centre Prague

    International Nuclear Information System (INIS)

    Belohlavek, O.

    2001-01-01

    The PET Centre Prague (www.homolka.cz/nm) was established in 1999 as the outcome of a joint project of the public Na Homolce Hospital and the Nuclear Research Institute Rez, plc, the Czech radiopharmaceutical producer. Technical and financial assistance was provided by the International Atomic Energy Agency, which perceived the Centre as its model project that could serve as a guide for the development of PET centres in countries sharing a comparable level of development with the Czech Republic. The article maps the history of the project, its design, workplace lay-out and equipment, radiation protection arrangements and spectrum of the first approx. 3000 investigations. (author)

  20. Logistics centres development in Latvia

    Directory of Open Access Journals (Sweden)

    I. Kabashkin

    2007-12-01

    Full Text Available In the situation where a large increase in trade and freight transport volumes in the Baltic Sea region (BSR is expected and in which the BSR is facing a major economic restructuring, eff orts to achieve more integrated and sustainable transport and communication links within the BSR are needed. One of these eff orts is the development of logistics centres (LCs and their networking, which will continue to have an impact on improving communication links, spatial planning practices and approaches, logistics chain development and the promotion of sustainable transport modes. These factors will refl ect on logistics processes both in major gateway cities and in remote BSR areas. The importance of logistics systems as a whole is not seen clearly enough. Logistics actors see that logistics operations are not appreciated as much as other fi elds of activity. In addition, logistics centres and the importance of logistics activities to the business life of areas and the employment rate should be brought up better. In the paper main goal and tasks of national approach to LCs development are discussed. Strategic focus of new activities in this area is on the integration of various networks within and between logistics centres in order to improve and develop the quality of logistics networks as well as to spatially widen the networking activities. The key objectives are to integrate the links between logistics centres, ports and other logistics operators in a functional and sustainable way, to promote spatial integration by creating sustainable and integrated approaches to spatial planning of logistics centres and transport infrastructure, to improve ICT-based networking and communication practices of the fi elds of transport and logistics and to increase the competence of logistics centres and associated actors by organising educational and training events. The current activities include, for example, the creation of measures for transport networking and

  1. Trends in Data Centre Energy Consumption under the European Code of Conduct for Data Centre Energy Efficiency

    Directory of Open Access Journals (Sweden)

    Maria Avgerinou

    2017-09-01

    Full Text Available Climate change is recognised as one of the key challenges humankind is facing. The Information and Communication Technology (ICT sector including data centres generates up to 2% of the global CO2 emissions, a number on par to the aviation sector contribution, and data centres are estimated to have the fastest growing carbon footprint from across the whole ICT sector, mainly due to technological advances such as the cloud computing and the rapid growth of the use of Internet services. There are no recent estimations of the total energy consumption of the European data centre and of their energy efficiency. The aim of this paper is to evaluate, analyse and present the current trends in energy consumption and efficiency in data centres in the European Union using the data submitted by companies participating in the European Code of Conduct for Data Centre Energy Efficiency programme, a voluntary initiative created in 2008 in response to the increasing energy consumption in data centres and the need to reduce the related environmental, economic and energy supply security impacts. The analysis shows that the average Power Usage Effectiveness (PUE of the facilities participating in the programme is declining year after year. This confirms that voluntary approaches could be effective in addressing climate and energy issue.

  2. Nuclear translocation of glutathione transferase omega is a progression marker in Barrett's esophagus

    DEFF Research Database (Denmark)

    Piaggi, Simona; Marchi, Santino; Ciancia, Eugenio

    2009-01-01

    Barrett's esophagus (BE) represents a major risk factor for esophageal adenocarcinoma (AC). For this reason, patients with BE are subjected to a systematic endoscopic surveillance to detect initial evolution towards non-invasive neoplasia (NiN) and cancer, that eventually occurs only in a small......-S-transferase-omega 1 could be involved in the stress response of human cells playing a role in the cancer progression of Barrett's esophagus. Its immunohistochemical detection could represent a useful tool in the grading of Barrett's disease.......N in BE and to understand the mechanisms of the progression from BE to AC. We investigated the expression and subcellular localization of GSTO1 in biopsies from patients with BE and in human cancer cell lines subjected to heath shock treatment. A selective nuclear localisation of GSTO1 was found in 16/16 biopsies with low...

  3. Colour centres in germanosilicate glass and optical fibres

    International Nuclear Information System (INIS)

    Neustruev, V.B.

    1994-01-01

    This review presents the state of the art of the study of germanium-related colour centres in silica glass and silica-based fibres. Most attention is concentrated on the dominant colour centres such as the Ge-related oxygen-deficient centres and paramagnetic Ge(n) centres, all of them having ultraviolet absorption bands. The hypothetical models and formation mechanisms proposed so far for these colour centres are discussed in detail. The origins of the models and formation mechanisms and their weak and strong points are analysed. The origin of the less well studied Ge-related colour centres in the visible spectral range (GeH, GeX, drawing-dependent defects) is also discussed. (author)

  4. HISTORIC CENTRE(S OF BARCELONA: PRACTICAL AND SYMBOLIC ELEMENTS IN TRADITIONAL URBAN SPACE

    Directory of Open Access Journals (Sweden)

    Verónica Martínez Robles

    2007-09-01

    The model of compact city that Barcelona aims, has required the renewal of its historical areas, and in order to improve their level of centrality, taking into account, that in addition of its historical centre “Ciutat Vella”, Barcelona contains diverse traditional neighborhoods each of them having their own historical centre. The difference centre‐periphery should also be perceived among these other historical centers. Integration should not be confused with standardization, neither differentiation with segregation.

  5. Person-centred healthcare research: a personal influence

    Directory of Open Access Journals (Sweden)

    * Corresponding author: University of Windesheim, Zwolle, The Netherlands Email: am.vandenberg@windesheim.nl Submitted for publication: 3rd November 2017 Accepted for publication: 12th March 2018 Published: 16th May 2018 https://doi.org/10.19043/ipdj.81.011 Abstract Context: This critical reflection is about the positive effects for educational and research settings of participation in a two-day programme entitled ‘Using participatory action research and appreciative inquiry to research healthcare practice’. Aims: To reflect on the journey of positive developments in research and education that started with participation in this programme. Using Caring Conversations (Dewar, 2011 as a reflective framework of questions, this article discusses the journey in order to encourage others to consider the approach of appreciative inquiry to bring to life the concept of co-creation in research and education. Conclusions and implications for practice: Participation in this programme has led to the implementation of a variety of actions in educational and research settings. Central to all these actions is an appreciative approach to co-creation as a counterpart to today’s prevailing problem-based viewpoint. A possible factor behind these developments was the power of vulnerability experienced during the programme, a shared process of transformational learning. Implications for practice: This critical reflection: Provides an invitation to shift from a problem-based focus to a positive revolution Provides an appreciative reflective story about the power of vulnerability as an inspiration for others to move out of their comfort zone and seek to discover their own exceptionality Supports a shift from a facilitator-led to a co-creation approach in doing research and teaching with older adults Keywords: Emotional touchpoints, appreciative inquiry, Caring Conversations, practice development, co-creation, transformational learning theory   IDEAS AND INFLUENCES Person-centred healthcare research: a personal influence Hazel M. Chapman

    2018-05-01

    Full Text Available This commentary assesses the contribution made by the person-centred healthcare research of McCormack et al (2017 to research methodology and our ability to evaluate an organisation’s claims to be person-centred. It discusses the importance of person-centred ethical approaches within rigorous research methodologies.

  6. The CCCB is a cultural centre, not a tourist centre

    Directory of Open Access Journals (Sweden)

    Elena Xirau

    2004-04-01

    Full Text Available Last February, Barcelona's Centre of Contemporary Culture (CCCB celebrated its first ten years in existence. During this time, this institution has looked to be a showcase to the most modern and innovative cultural expressions focused on reflecting on the concept of the city. In this interview, Josep Ramoneda offers his personal view, as the CCCB's director. He talks of how this cultural project was born, of how the concept of the institution took shape in the CCCB, of its relations with Barcelona's Strategic Plan, of how the project has evolved, of the architectural remodelling of the Casa de la Caritat building for its conversion into a cultural centre, of the relations with other institutions and its future.

  7. Maize w3 disrupts homogentisate solanesyl transferase (ZmHst) and reveals a plastoquinone-9 independent path for phytoene desaturation and tocopherol accumulation in kernels

    Science.gov (United States)

    Maize white seedling 3 (w3) has been used to study carotenoid deficiency for almost 100 years, although its genetic basis remained unknown. We show here that w3 phenotype is caused by disruption of homogentisate solanesyl transferase (HST), which catalyzes the first committed step in plastoquinone-9...

  8. Presentation of TVO's visitor's centre

    International Nuclear Information System (INIS)

    Aemmaelae, V.M.

    1993-01-01

    There are four nuclear power plant units in Finland, two of which are PWR's owned by Imatran Voima Oy. The two BWR units are located at Olkiluoto and owned by Teollisuuden Voima Oy. This presentation tells about TVO's concept of informing the visitors at Olkiluoto. At the site there are located, in addition to the two nuclear power plant units, the intermediate storage for spent fuel, the repository for low and medium-active waste as well as the training centre. At the Olkiluoto Visitor's Centre all the activities of the company are presented using varied audio-visual aids. The centre has several exhibits and there are also different installations to show how the plant works. (author)

  9. Technical support and emergency centre

    International Nuclear Information System (INIS)

    Bohun, L.; Kapisovsk y, M.

    1997-01-01

    This paper presents technical support and emergency management center which will be on two places: Mochovce NPP Emergency Centre (Technical support center and Support working center) and Reserve Emergency Centre in Levice (Reserve emergency center and Environmental Evaluation Center). The main aims of the emergency management centers are: the management and coordination of all persons and organisations; provision of the all information needed to evaluation of the accident and its mitigation; continuous evaluation of the potential or real radiological consequences; taking measure for an early notification of the governmental bodies and the organizations, warning and protection of the public; and other aims. In the next part the data for technical support and emergency centre are discussed

  10. Patient-centred care: a review for rehabilitative audiologists.

    Science.gov (United States)

    Grenness, Caitlin; Hickson, Louise; Laplante-Lévesque, Ariane; Davidson, Bronwyn

    2014-02-01

    This discussion paper aims to synthesise the literature on patient-centred care from a range of health professions and to relate this to the field of rehabilitative audiology. Through review of the literature, this paper addresses five questions: What is patient-centred care? How is patient-centred care measured? What are the outcomes of patient-centred care? What are the factors contributing to patient-centred care? What are the implications for audiological rehabilitation? Literature review and synthesis. Publications were identified by structured searches in PubMed, Cinahl, Web of Knowledge, and PsychInfo, and by inspecting the reference lists of relevant articles. Few publications from within the audiology profession address this topic and consequently a review and synthesis of literature from other areas of health were used to answer the proposed questions. This paper concludes that patient-centred care is in line with the aims and scope of practice for audiological rehabilitation. However, there is emerging evidence that we still need to inform the conceptualisation of patient-centred audiological rehabilitation. A definition of patient-centred audiological rehabilitation is needed to facilitate studies into the nature and outcomes of it in audiological rehabilitation practice.

  11. The Aube centre. 1997 statement

    International Nuclear Information System (INIS)

    1998-09-01

    Since January 1992 the Aube centre ensures the storage of 90% of the short life radioactive wastes produced in France. This educational booklet describes the organization of the activities in the centre from the storage of wastes to the radioactivity surveillance of the environment (air, surface and ground waters, river sediments, plants and milk). (J.S.)

  12. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Merchant, Michael L. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Division of Nephrology, Department of Medicine, University of Louisville, Louisville, KY 40292 (United States); Prough, Russell A. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States); Williams, Jessica D. [University of Cincinnati College of Medicine, Internal Medicine, Cincinnati, OH 45267 (United States); Prabhu, Sumanth D. [Division of Cardiovascular Disease, University of Alabama-Birmingham, Birmingham, AL 35294 (United States); Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States)

    2015-06-01

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  13. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    International Nuclear Information System (INIS)

    Conklin, Daniel J.; Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid; Merchant, Michael L.; Prough, Russell A.; Williams, Jessica D.; Prabhu, Sumanth D.; Bhatnagar, Aruni

    2015-01-01

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  14. NCBI nr-aa BLAST: CBRC-SARA-01-0522 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-0522 ref|YP_001499570.1| Peptidyl-tRNA hydrolase [Rickettsia massiliae... MTU5] gb|ABV85023.1| Peptidyl-tRNA hydrolase [Rickettsia massiliae MTU5] YP_001499570.1 4.7 36% ...

  15. Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin.

    Science.gov (United States)

    Schlünzen, Frank; Pyetan, Erez; Fucini, Paola; Yonath, Ada; Harms, Jörg M

    2004-12-01

    Tiamulin, a prominent member of the pleuromutilin class of antibiotics, is a potent inhibitor of protein synthesis in bacteria. Up to now the effect of pleuromutilins on the ribosome has not been determined on a molecular level. The 3.5 A structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin provides for the first time a detailed picture of its interactions with the 23S rRNA, thus explaining the molecular mechanism of the antimicrobial activity of the pleuromutilin class of antibiotics. Our results show that tiamulin is located within the peptidyl transferase center (PTC) of the 50S ribosomal subunit with its tricyclic mutilin core positioned in a tight pocket at the A-tRNA binding site. Also, the extension, which protrudes from its mutilin core, partially overlaps with the P-tRNA binding site. Thereby, tiamulin directly inhibits peptide bond formation. Comparison of the tiamulin binding site with other PTC targeting drugs, like chloramphenicol, clindamycin and streptogramins, may facilitate the design of modified or hybridized drugs that extend the applicability of this class of antibiotics.

  16. Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3-epi-deoxynivalenol

    Directory of Open Access Journals (Sweden)

    Yousef I. Hassan

    2016-09-01

    Full Text Available Deoxynivalenol (DON is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC. In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding.

  17. Cofactors in the RNA World

    Science.gov (United States)

    Ditzler, Mark A.

    2014-01-01

    RNA world theories figure prominently in many scenarios for the origin and early evolution of life. These theories posit that RNA molecules played a much larger role in ancient biology than they do now, acting both as the dominant biocatalysts and as the repository of genetic information. Many features of modern RNA biology are potential examples of molecular fossils from an RNA world, such as the pervasive involvement of nucleotides in coenzymes, the existence of natural aptamers that bind these coenzymes, the existence of natural ribozymes, a biosynthetic pathway in which deoxynucleotides are produced from ribonucleotides, and the central role of ribosomal RNA in protein synthesis in the peptidyl transferase center of the ribosome. Here, we uses both a top-down approach that evaluates RNA function in modern biology and a bottom-up approach that examines the capacities of RNA independent of modern biology. These complementary approaches exploit multiple in vitro evolution techniques coupled with high-throughput sequencing and bioinformatics analysis. Together these complementary approaches advance our understanding of the most primitive organisms, their early evolution, and their eventual transition to modern biochemistry.

  18. Review of CERN Data Centre Infrastructure

    International Nuclear Information System (INIS)

    Andrade, P; Bell, T; Van Eldik, J; McCance, G; Panzer-Steindel, B; Coelho dos Santos, M; Traylen and, S; Schwickerath, U

    2012-01-01

    The CERN Data Centre is reviewing strategies for optimizing the use of the existing infrastructure and expanding to a new data centre by studying how other large sites are being operated. Over the past six months, CERN has been investigating modern and widely-used tools and procedures used for virtualisation, clouds and fabric management in order to reduce operational effort, increase agility and support unattended remote data centres. This paper gives the details on the project's motivations, current status and areas for future investigation.

  19. Review of CERN Data Centre Infrastructure

    CERN Document Server

    Andrade, P; van Eldik, J; McCance, G; Panzer-Steindel, B; Coelho dos Santos, M; Traylen, S; Schwickerath, U

    2012-01-01

    The CERN Data Centre is reviewing strategies for optimizing the use of the existing infrastructure and expanding to a new data centre by studying how other large sites are being operated. Over the past six months, CERN has been investigating modern and widely-used tools and procedures used for virtualisation, clouds and fabric management in order to reduce operational effort, increase agility and support unattended remote data centres. This paper gives the details on the project’s motivations, current status and areas for future investigation.

  20. Response of Glutathione and Glutathione S-transferase in Rice Seedlings Exposed to Cadmium Stress

    Directory of Open Access Journals (Sweden)

    Chun-hua ZHANG

    2008-03-01

    Full Text Available A hydroponic culture experiment was done to investigate the effect of Cd stress on glutathione content (GSH and glutathione S-transferase (GST, EC 2.5.1.18 activity in rice seedlings. The rice growth was severely inhibited when Cd level in the solution was higher than 10 mg/L. In rice shoots, GSH content and GST activity increased with the increasing Cd level, while in roots, GST was obviously inhibited by Cd treatments. Compared with shoots, the rice roots had higher GSH content and GST activity, indicating the ability of Cd detoxification was much higher in roots than in shoots. There was a significant correlation between Cd level and GSH content or GST activity, suggesting that both parameters may be used as biomarkers of Cd stress in rice.

  1. Comparison of planned menus and centre characteristics with foods and beverages served in New York City child-care centres.

    Science.gov (United States)

    Breck, Andrew; Dixon, L Beth; Kettel Khan, Laura

    2016-10-01

    The present study evaluated the extent to which child-care centre menus prepared in advance correspond with food and beverage items served to children. The authors identified centre and staff characteristics that were associated with matches between menus and what was served. Menus were collected from ninety-five centres in New York City (NYC). Direct observation of foods and beverages served to children were conducted during 524 meal and snack times at these centres between April and June 2010, as part of a larger study designed to determine compliance of child-care centres with city health department regulations for nutrition. Child-care centres were located in low-income neighbourhoods in NYC. Overall, 87 % of the foods and beverages listed on the menus or allowed as substitutions were served. Menu items matched with foods and beverages served for all major food groups by >60 %. Sweets and water had lower match percentages (40 and 32 %, respectively), but water was served 68 % of the time when it was not listed on the menu. The staff person making the food and purchasing decisions predicted the match between the planned or substituted items on the menus and the foods and beverages served. In the present study, child-care centre menus included most foods and beverages served to children. Menus planned in advance have potential to be used to inform parents about which child-care centre to send their child or what foods and beverages their enrolled children will be offered throughout the day.

  2. Comparison of planned menus and centre characteristics with foods and beverages served in New York City child-care centres

    Science.gov (United States)

    Breck, Andrew; Dixon, L Beth; Khan, Laura Kettel

    2016-01-01

    Objective The present study evaluated the extent to which child-care centre menus prepared in advance correspond with food and beverage items served to children. The authors identified centre and staff characteristics that were associated with matches between menus and what was served. Design Menus were collected from ninety-five centres in New York City (NYC). Direct observation of foods and beverages served to children were conducted during 524 meal and snack times at these centres between April and June 2010, as part of a larger study designed to determine compliance of child-care centres with city health department regulations for nutrition. Setting Child-care centres were located in low-income neighbourhoods in NYC. Results Overall, 87% of the foods and beverages listed on the menus or allowed as substitutions were served. Menu items matched with foods and beverages served for all major food groups by > 60%. Sweets and water had lower match percentages (40 and 32%, respectively), but water was served 68% of the time when it was not listed on the menu. The staff person making the food and purchasing decisions predicted the match between the planned or substituted items on the menus and the foods and beverages served. Conclusions In the present study, child-care centre menus included most foods and beverages served to children. Menus planned in advance have potential to be used to inform parents about which child-care centre to send their child or what foods and beverages their enrolled children will be offered throughout the day. PMID:27280341

  3. Inhibition of the recombinant cattle tick Rhipicephalus (Boophilus) annulatus glutathione S-transferase.

    Science.gov (United States)

    Guneidy, Rasha A; Shahein, Yasser E; Abouelella, Amira M K; Zaki, Eman R; Hamed, Ragaa R

    2014-09-01

    Rhipicephalus (Boophilus) annulatus is a bloodsucking ectoparasite that causes severe production losses in the cattle industry. This study aims to evaluate the in vitro effects of tannic acid, hematin (GST inhibitors) and different plant extracts (rich in tannic acid) on the activity of the recombinant glutathione S-transferase enzyme of the Egyptian cattle tick R. annulatus (rRaGST), in order to confirm their ability to inhibit the parasitic essential detoxification enzyme glutathione S-transferase. Extraction with 70% ethanol of Hibiscus cannabinus (kenaf flowers), Punica granatum (red and white pomegranate peel), Musa acuminata (banana peel) (Musaceae), Medicago sativa (alfalfa seeds), Tamarindus indicus (seed) and Cuminum cyminum (cumin seed) were used to assess: (i) inhibitory capacities of rRaGST and (ii) their phenolic and flavonoid contents. Ethanol extraction of red pomegranate peel contained the highest content of phenolic compounds (29.95mg gallic acid/g dry tissue) compared to the other studied plant extracts. The highest inhibition activities of rRaGST were obtained with kenaf and red pomegranate peel (P. granatum) extracts with IC50 values of 0.123 and 0.136mg dry tissue/ml, respectively. Tannic acid was the more effective inhibitor of rRaGST with an IC50 value equal to 4.57μM compared to delphinidine-HCl (IC50=14.9±3.1μM). Gossypol had a weak inhibitory effect (IC50=43.7μM), and caffeic acid had almost no effect on tick GST activity. The IC50 values qualify ethacrynic acid as a potent inhibitor of rRaGST activity (IC50=0.034μM). Cibacron blue and hematin showed a considerable inhibition effect on rRaGST activity, and their IC50 values were 0.13μM and 7.5μM, respectively. The activity of rRaGST was highest for CDNB (30.2μmol/min/mg protein). The enzyme had also a peroxidatic activity (the specific activity equals 26.5μmol/min/mg protein). Both tannic acid and hematin inhibited rRaGST activity non-competitively with respect to GSH and

  4. A reference regional nuclear fuel centre

    International Nuclear Information System (INIS)

    1978-01-01

    A nuclear fuel centre groups the facilities for spent fuel reprocessing, plutonium fuel fabrication, waste conditioning, and interim storage on a single site. The technical aspects of safety and protection, and the socio-economic consequences of two types of centre have been studied. The reference centre has an initial reprocessing capacity of 1500 tonnes. This capacity is quadrupled by the construction of two new units in 15 years. The other centre considered is a quarter of this size. A description is given of the processes used, the personal and capital requirements for construction and operation of the plant, the transport of radioactive waste and products, and the quantities involved. The local radiological impact is low and could be further reduced to a level well below that of natural radioactivity. The resulting increase in economic activity, employment, income redistribution and the new infrastructure requirements are estimated for a rural or semi-rural region. Measures to prevent tension are proposed. The impact of the host country's balance of payments, finances, employment situation and technological knowhow is evaluated. The original centre is compared with equivalent facilities scattered geographically

  5. The Aube storage centre: Annual report 2010

    International Nuclear Information System (INIS)

    2011-01-01

    After a presentation of the Aube storage centre, a storage centre for low and intermediate activity nuclear wastes, this report gives an overview of measures related to nuclear security, to radioprotection and to nuclear safety. It indicates the incidents and accidents which occurred in 2010, describes how the centre's wastes are managed, and indicates the actions performed in terms of public information

  6. Solution Structure of Archaeoglobus fulgidis Peptidyl-tRNA Hydrolase(Pth2) Provides Evidence for an Extensive Conserved Family of Pth2 Enzymes in Archaea, Bacteria and Eukaryotes.

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Robert; Mirkovic, Nebojsa; Goldsmith-Fischman, Sharon; Acton, Thomas; Chiang, Yiwen; Huang, Yuanpeng; Ma, LiChung; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Rost, Burkhard; Honig, Barry; Murray, Diana; Montelione, Gaetano

    2005-11-01

    The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123-residue (13.6 kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four a-helices and a mixed b-sheet consisting of four parallel and anti-parallel b-strands, where the a-helices sandwich the b-sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii and Sulfolobus solfataricus, reveals that AF2095 is a peptidyl-tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Database but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active-site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.

  7. CANDU 9 Control Centre Mockup

    International Nuclear Information System (INIS)

    Webster, A.; Macbeth, M.J.

    1996-01-01

    This paper provides a summary of the design process being followed, the benefits of applying a systematic design using human factors engineering, presents an overview of the CANDU 9 control centre mockup facility, illustrates the control centre mockup with photographs of the 3D CADD model and the full scale mockup, and provides an update on the current status of the project. (author)

  8. Leveraging management information in improving call centre productivity

    Directory of Open Access Journals (Sweden)

    Manthisana Mosese

    2016-04-01

    Objectives: This research explored the use of management information and its impact on two fundamental functions namely, improving productivity without compromising the quality of service, in the call centre of a well-known South African fashion retailer, Edcon. Following the implementation of the call centre technology project the research set out to determine how Edcon can transform their call centre to improve productivity and customer service through effective utilisation of their management information. Method: Internal documents and reports were analysed to provide the basis of evaluation between the measures of productivity prior to and post the implementation of a technology project at Edcon’s call centre. Semi-structured in-depth and group interviews were conducted to establish the importance and use of management information in improving productivity and customer service. Results: The results indicated that the availability of management information has indeed contributed to improved efficiency at the Edcon call centre. Although literature claims that there is a correlation between a call centre technology upgrade and improvement in performance, evident in the return on investment being realised within a year or two of implementation, it fell beyond the scope of this study to investigate the return on investment for Edcon’s call centre. Conclusion: Although Edcon has begun realising benefits in improved productivity in their call centre from their available management information, information will continue to play a crucial role in supporting management with informed decisions that will improve the call centre operations. [pdf to follow

  9. Mucin-type O-glycosylation is controlled by short- and long-range glycopeptide substrate recognition that varies among members of the polypeptide GalNAc transferase family

    DEFF Research Database (Denmark)

    Revoredo, Leslie; Wang, Shengjun; Bennett, Eric Paul

    2016-01-01

    A large family of UDP-GalNAc:polypeptide GalNAc transferases (ppGalNAc-Ts) initiates and defines sites of mucin-type Ser/Thr-O-GalNAc glycosylation. Family members have been classified into peptide- and glycopeptide-preferring subfamilies, although both families possess variable activities agains...

  10. Centre for Building Simulation. Basis for establishing a centre; Center for Bygningssimulering - Idegrundlag for etablering af center

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, Joergen Erik; Karlshoej, J.; Bacher, P.; Johnsen, K.; Olesen, B.W.; Rode, C.; Heller, A.

    2012-12-15

    The purpose of the project was to create the basis for the establishment of a Centre for Building Simulation focusing on the use of advanced building energy simulations to obtain electricity and heat savings. The project of trying to make a Centre for Building Simulation in Denmark was based on interviews with future users and partners with an interest in further development of Denmark's leading position in this field. Friday 29th October, 2010, a ''Workshop on the establishment of the Centre for Building Simulation'' was organized at DTU. Approximately 90 national and international participants were present. The workshop structure and results are described in enclosure 1. The primary purpose of the workshop was to establish consensus on the needs of architects and consultants in Denmark in relation to building simulation, and create the concept for a Danish Centre for Building Simulation. As a result of the workshop the idea grew that the centre will combine research and development activities of the Danish building simulation and develops future intelligent simulation tools with a focus on the use of advanced building energy simulations to achieve sustainable construction. These programs need to interact closely with Building Information Modelling, BIM, where the construction process is connected to a digital building model. In addition, various financing options were considered for the operation of the centre with an initial time horizon of 5-10 years. Based on results from the workshop, interviews with future users and partners, a large application was written to the Danish National Research Council, 7th application round - Centre of Excellence, 29 November 2011 (enclosure 3) entitled ''Centre for Intelligent Building Information Modelling iBIM''. The work on the application resulted in a great deal of knowledge gathered and adapted during the whole process of preparing the application. Unfortunately, the application

  11. The Imperial College Thermophysical Properties Data Centre

    Science.gov (United States)

    Angus, S.; Cole, W. A.; Craven, R.; de Reuck, K. M.; Trengove, R. D.; Wakeham, W. A.

    1986-07-01

    The IUPAC Thermodynamic Tables Project Centre in London has at its disposal considerable expertise on the production and utilization of high-accuracy equations of state which represent the thermodynamic properties of substances. For some years they have been content to propagate this information by the traditional method of book production, but the increasing use of the computer in industry for process design has shown that an additional method was needed. The setting up of the IUPAC Transport Properties Project Centre, also at Imperial College, whose products would also be in demand by industry, afforded the occasion for a new look at the problem. The solution has been to set up the Imperial College Thermophysical Properties Data Centre, which embraces the two IUPAC Project Centres, and for it to establish a link with the existing Physical Properties Data Service of the Institution of Chemical Engineers, thus providing for the dissemination of the available information without involving the Centres in problems such as those of marketing and advertising. This paper outlines the activities of the Centres and discusses the problems in bringing their products to the attention of industry in suitable form.

  12. EVALUATION OF ENVIRONMENTAL EDUCATION CENTRES- A ...

    African Journals Online (AJOL)

    centres in South Africa revealed that some field .... psychomotor goals suitable for each age group? * Did the officer have a proper ..... education centres, spending two to four weeks at a ... you must be willing to suspend judgement, to hold in ...

  13. Differential transcription of cytochrome P450s and glutathione S transferases in DDT-susceptible and resistant Drosophila melanogaster strains in response to DDT and oxidative stress

    Science.gov (United States)

    Metabolic DDT resistance in Drosophila melanogaster has previously been associated with constitutive over-transcription of cytochrome P450s. Increased P450 activity has also been associated with increased oxidative stress. In contrast, over-transcription of glutathione S transferases (GSTs) has been...

  14. Formaldehyde in the Galactic Centre

    International Nuclear Information System (INIS)

    Cohen, R.J.; Few, R.W.

    1981-01-01

    Formaldehyde 6-cm absorption in the direction of the Galactic Centre has been surveyed using the Jodrell Bank MK II radio telescope (beam-width 10 x 9 arcmin). The observations sample the region - 2 0 = 0 and - 0 0 .5 = 0 .5, with a velocity range of 620 km s -1 , a velocity resolution of 2.1 km s -1 and an rms noise level of approximately 0.03 K. The data are presented as contour maps showing line temperature as a function of latitude and velocity (b-V maps) and as a function of longitude and velocity (l-V maps). Similar maps of the line-to-continuum ratio are also presented. The radial distribution of formaldehyde (H 2 CO) in the Galactic Centre region is derived using two different kinematic models which give similar results. Formaldehyde is strongly concentrated in the Galactic Centre in a layer of latitude extent approximately 0 0 .5 and longitude extent approximately 4 0 which contains one quarter of all the H 2 CO in the Galaxy. The distribution is centred on l approximately 1 0 . The individual H 2 CO features are described in detail. (author)

  15. Regional Centres for Space Science and Technology Education and ICG Information Centres affiliated to the United Nations

    Science.gov (United States)

    Gadimova, S.; Haubold, H. J.

    2009-06-01

    Based on resolutions of the United Nations General Assembly, Regional Centres for Space Science and Technology Education were established in India, Morocco, Nigeria, Brazil and Mexico. Simultaneously, education curricula were developed for the core disciplines of remote sensing, satellite communications, satellite meteorology, and space and atmospheric science. This paper provides a brief summary on the status of the operation of the regional centres with a view to use them as information centres of the International Committee on Global Navigation Satellite Systems (ICG), and draws attention to their educational activities.

  16. The Structural Integrity Centre

    International Nuclear Information System (INIS)

    Tomkins, B.

    1987-01-01

    The paper concerns the development and work of the Structural Integrity Centre (SIC) at Risley Nuclear Laboratories, United Kingdom. The centre was set up to provide authoritative advice to plant designers and operators on the integrity and life assessment of structures and components across the reactor projects in the United Kingdom. A description is given of the structure and role of the SIC, as well as the Structural Integrity Assessment work. The assessment methods are described for thermally loaded structures and welded structures. Finally, defect significance assessment and environmental effects are outlined. (U.K.)

  17. How European centres diagnose, treat, and prevent CIED infections

    DEFF Research Database (Denmark)

    Bongiorni, Maria Grazia; Marinskis, Germanas; Lip, Gregory Y H

    2012-01-01

    in most centres and is substantially under 2% in the majority of centres interviewed. However, there are still differences in terms of prophylactic antibiotic therapy: 8.9% of the centres administer oxacillin as preoperative treatment, 4.4% of them do not give any antibiotic therapy, all centres use some...

  18. THE ELUSIVENESS OF LEARNER-CENTRED TEACHING

    Directory of Open Access Journals (Sweden)

    Ervin Kovačević

    2016-03-01

    Full Text Available This research will explore teaching styles of university professors. Teaching style is an umbrella term for teaching decisions made during the entire teaching process – planning, delivery, and evaluation. Contemporary university teachers are advised to adopt the learner-centred teaching style which is assumed to produce remarkable possibilities. In the Fall Semester 2015 fifty-two respondents in different faculties of International University of Sarajevo were surveyed using The Principles of Adult Learning Scale inventory designed by Gary J. Conti. Inventory scores were calculated according to guidelines suggested by the author of the inventory. The scores revealed that majority of respondents strongly supported teacher-centred rather than learner-centred styles of instruction. Scores were analysed on gender lines and across three different faculties, namely: Arts and Social Sciences; Business and Administration; Engineering and Natural Sciences. In all five groups none of the seven teaching style indicators was found to conform with the learner-centred teaching criteria. There was no statistically significant difference between the two genders’ preference for a teaching style. And there was no statistically significant difference between teaching style preference across the three different faculties.The results of this research imply that the learner-centred style of instruction is not frequently implemented. Secondly, the results indicate that the requirements necessary for proper application of the learner-centred teaching style are not easy to meet in current written and unwritten norms. Finally, the results show that traditional teaching styles, which have been preserved in different scientific fields, still predominate in universities.

  19. Identification and suppression of the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase in Zea mays L.

    Science.gov (United States)

    Marita, Jane M; Hatfield, Ronald D; Rancour, David M; Frost, Kenneth E

    2014-06-01

    Grasses, such as Zea mays L. (maize), contain relatively high levels of p-coumarates (pCA) within their cell walls. Incorporation of pCA into cell walls is believed to be due to a hydroxycinnamyl transferase that couples pCA to monolignols. To understand the role of pCA in maize development, the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase (pCAT) was isolated and purified from maize stems. Purified pCAT was subjected to partial trypsin digestion, and peptides were sequenced by tandem mass spectrometry. TBLASTN analysis of the acquired peptide sequences identified a single full-length maize cDNA clone encoding all the peptide sequences obtained from the purified enzyme. The cDNA clone was obtained and used to generate an RNAi construct for suppressing pCAT expression in maize. Here we describe the effects of suppression of pCAT in maize. Primary screening of transgenic maize seedling leaves using a new rapid analytical platform was used to identify plants with decreased amounts of pCA. Using this screening method, mature leaves from fully developed plants were analyzed, confirming reduced pCA levels throughout plant development. Complete analysis of isolated cell walls from mature transgenic stems and leaves revealed that lignin levels did not change, but pCA levels decreased and the lignin composition was altered. Transgenic plants with the lowest levels of pCA had decreased levels of syringyl units in the lignin. Thus, altering the levels of pCAT expression in maize leads to altered lignin composition, but does not appear to alter the total amount of lignin present in the cell walls. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  20. Scavenger hunt in the CERN Computing Centre

    CERN Multimedia

    CERN Bulletin

    2013-01-01

    Hidden among the racks of servers and disks in the CERN Computing Centre, you’ll find Hawaiian dancers, space aliens, gorillas… all LEGO® figurines! These characters were placed about the Centre for the arrival of Google’s Street View team for the world to discover.   PLEASE NOTE THAT THE COMPETITION IS OVER. ONLY FOR REFERENCE, HERE IS THE ORIGINAL ARTICLE. We’re pleased to announce our first global scavenger hunt! Spot three LEGO® figurines using Google’s Street View and you’ll be entered to win a gift of your choice from our CERN Gift Guide. A LEGO® figurine in the CERN Computing Centre, as seen on Google Street View. Here are the details: Find at least three LEGO® figurines hidden around the CERN Computing Centre using Google Street View.   Take screencaps of the figurines and e-mail the pictures to TreasureHunt-ComputingCentre@cern.ch. This email is no longer active.   The...

  1. The role of the sexual assault centre.

    LENUS (Irish Health Repository)

    Eogan, Maeve

    2013-02-01

    Sexual Assault Centres provide multidisciplinary care for men and women who have experienced sexual crime. These centres enable provision of medical, forensic, psychological support and follow-up care, even if patients chose not to report the incident to the police service. Sexual Support Centres need to provide a ring-fenced, forensically clean environment. They need to be appropriately staffed and available 24 hours a day, 7 days a week to allow prompt provision of medical and supportive care and collection of forensic evidence. Sexual Assault Centres work best within the context of a core agreed model of care, which includes defined multi-agency guidelines and care pathways, close links with forensic science and police services, and designated and sustainable funding arrangements. Additionally, Sexual Assault Centres also participate in patient, staff and community education and risk reduction. Furthermore, they contribute to the development, evaluation and implementation of national strategies on domestic, sexual and gender-based violence.

  2. Visitor centres at nuclear facility sites

    International Nuclear Information System (INIS)

    1993-01-01

    Communications strategies in the nuclear field are often based on the creation of visitor centres at nuclear facility sites. Today, the design, as well as the realization and management of such centres has become a specialized function, and its role is very complementary to the nuclear operator's. It also uses the latest technology in the field of audio-visual, experiment and interactivity. This publication contains the proceedings of an international seminar organized by the OECD Nuclear Energy Agency on the role of visitor centres at nuclear facility sites. It includes the main papers presented at this Seminar

  3. Student-Centred and Teacher-Centred Learning Environment in Pre-Vocational Secondary Education: Psychological Needs, and Motivation

    Science.gov (United States)

    Smit, Karin; de Brabander, Cornelis J.; Martens, Rob L.

    2014-01-01

    In this study the perception of psychological needs and motivation in a student-centred and a teacher-centred learning environment are compared, using Self Determination Theory as a framework. The self-report Intrinsic Motivation Inventory was completed by 230 students (mean age 16.1 years) in pre-vocational secondary education. School records on…

  4. Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria.

    Science.gov (United States)

    Oshodi, Y; Ojewunmi, O; Oshodi, T A; Ijarogbe, G T; Ogun, O C; Aina, O F; Lesi, Fea

    2017-09-01

    The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.

  5. Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

    Science.gov (United States)

    Kung, P C; Long, J C; McCaffrey, R P; Ratliff, R L; Harrison, T A; Baltimore, D

    1978-05-01

    Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

  6. The role of glutathione transferases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ćorić Vesna

    2016-01-01

    Full Text Available Mounting evidence suggest that members of the subfamily of cytosolic glutathione S-transferases (GSTs possess roles far beyond the classical glutathione-dependent enzymatic conjugation of electrophilic metabolites and xenobiotics. Namely, monomeric forms of certain GSTs are capable of forming protein: protein interactions with protein kinases and regulate cell apoptotic pathways. Due to this dual functionality of cytosolic GSTs, they might be implicated in both the development and the progression of renal cell carcinoma (RCC. Prominent genetic heterogeneity, resulting from the gene deletions, as well as from SNPs in the coding and non-coding regions of GST genes, might affect GST isoenzyme profiles in renal parenchyma and therefore serve as a valuable indicator for predicting the risk of cancer development. Namely, GSTs are involved in the biotransformation of several compounds recognized as risk factors for RCC. The most potent carcinogen of polycyclic aromatic hydrocarbon diol epoxides, present in cigarette smoke, is of benzo(apyrene (BPDE, detoxified by GSTs. So far, the relationship between GST genotype and BPDE-DNA adduct formation, in determining the risk for RCC, has not been evaluated in patients with RCC. Although the association between certain individual and combined GST genotypes and RCC risk has been debated in a the literature, the data on the prognostic value of GST polymorphism in patients with RCC are scarce, probably due to the fact that the molecular mechanism supporting the role of GSTs in RCC progression has not been clarified as yet.

  7. Isolation and purification of glutathione S-transferases from Brachionus plicatilis and B. calyciflorus (Rotifera).

    Science.gov (United States)

    Bowman, B P; Snell, T W; Cochrane, B J

    1990-01-01

    1. The enzyme glutathione S-transferase (GST), a critical element in xenobiotic metabolism, was isolated from the marine rotifer Brachionus plicatilis and its freshwater congener B. calyciflorus. 2. In B. plicatilis, GST comprised 4.2% of cytosolic protein and was present as three separate isozymes with mol. wts 30,000, 31,400 and 33,700. Specific activity of crude homogenates was 56 nmol min-1 mg-1 protein, while that of affinity chromatography purified GST was 1850. 3. In B. calyciflorus, GST was present as two isozymes with mol. wts of 26,300 and 28,500, representing 1.0% of cytosolic protein. Crude GST specific activity was 1750 nmol min-1 mg-1 protein and purified was 72,400. 4. Rotifer GSTs are unusual because they are monomers whereas all other animals thus far investigated posses dimeric GSTs.

  8. The centre of the action

    CERN Multimedia

    2008-01-01

    The CERN Control Centre (CCC) has all the ingredients of an action movie control room: hundreds of screens, technicians buzzing in and out, huge floor-to-ceiling windows revealing the looming vista of a mountain range, flashing lights, microphones… This is the place where not just the LHC, but the whole of CERN’s accelerator complex and technical support is based - truly the centre of the action at CERN.

  9. Defining and describing birth centres in the Netherlands - a component study of the Dutch Birth Centre Study.

    NARCIS (Netherlands)

    Hermus, M.A.A.; Boesveld, I.C.; Hilzert, M.; Franx, A.; Graaf, J.P. de; Steegers, E.A.P.; Wiegers, T.A.; Pal-de Bruin, K.M. van der

    2017-01-01

    Background: During the last decade, a rapid increase of birth locations for low-risk births, other than conventional obstetric units, has been seen in the Netherlands. Internationally some of such locations are called birth centres. The varying international definitions for birth centres are not

  10. Defining and describing birth centres in the Netherlands - a component study of the Dutch Birth Centre Study

    NARCIS (Netherlands)

    Hermus, Marieke A. A.; Boesveld, I. C.; Hitzert, Marrit M; Franx, A.; de Graaf, J. P.; Steegers, E. A P; Wiegers, Therese A.; van der Pal-de Bruin, Karin M.

    2017-01-01

    Background: During the last decade, a rapid increase of birth locations for low-risk births, other than conventional obstetric units, has been seen in the Netherlands. Internationally some of such locations are called birth centres. The varying international definitions for birth centres are not

  11. International Development Research Centre Act Loi sur le Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 juin 2009 ... research includes any scientific or technical inquiry or experimentation that is .... data centres and facilities for research and other activ- ities;. (b) initiate and ..... Loi sur la pension de la fonction publique ne s'applique pas aux ...

  12. Thermoluminescence of Z1 centres in Sr-doped KCl

    International Nuclear Information System (INIS)

    Kamavisdar, V.S.; Moholkar, S.C.; Deshmukh, B.T.

    1980-01-01

    It is well known for alkali halides doped with divalent metal impurities that exposure to high energetic radiation and subsequent F band bleaching leads to the formation of Z 1 centres. Optical absorption measurements have shown that a low concentration of Z 1 centres is produced along with F centres during irradiation without any optical bleaching. Now the question is whether Z 1 centres are really formed along with F centres during irradiation. The aim of the present paper was to study the formation of a small amount of Z 1 centres during irradiation with the help of optical absorption and thermoluminescence measurements. The crystals of KCl:Sr were exposed to γ-rays for different doses. The TL curve for the crystal exposed to a minimum dose of γ-rays shows a TL peak at 457 K and a weak shoulder in the region 400 K to 408 K. The TL curve of the crystal exposed to maximum dose of rays shows the peak at 408 K with a greater intensity. Upon F band bleaching 408 K peak increases in intensity and optical absorption is also broadened. It is shown that the peak at 457 K is due to F centres and the peak at 408 K is due to Z 1 centres. These results clearly show that a small anount of Z 1 centres is really formed along with F centres during irradiation. (author)

  13. Elderly Care Centre

    Science.gov (United States)

    Wagiman, Aliani; Haja Bava Mohidin, Hazrina; Ismail, Alice Sabrina

    2016-02-01

    The demand for elderly centre has increased tremendously abreast with the world demographic change as the number of senior citizens rose in the 21st century. This has become one of the most crucial problems of today's era. As the world progress into modernity, more and more people are occupied with daily work causing the senior citizens to lose the care that they actually need. This paper seeks to elucidate the best possible design of an elderly care centre with new approach in order to provide the best service for them by analysing their needs and suitable activities that could elevate their quality of life. All these findings will then be incorporated into design solutions so as to enhance the living environment for the elderly especially in Malaysian context.

  14. Colour centre-free perovskite single crystals

    International Nuclear Information System (INIS)

    Petit, Pierre-Olivier; Petit, Johan; Goldner, Philippe; Viana, Bruno

    2009-01-01

    Yb 3+ :YAlO 3 (YAP) and Yb 3+ :GdAlO 3 (GAP) are interesting 1 μm high-power laser media thanks to their very good thermo-mechanical properties. However, as-grown perovskite single crystals exhibit colour centres. Parasitic thermal load generated by these centres is deleterious for high-power laser action and can lead to crystal damages. Moreover these defects decrease Yb 3+ lifetime. They are related to trapped holes on the oxygen network. In the present work, several schemes to remove colour centres are presented. Attention is focused on cerium codoping, thermal annealing under reducing atmosphere and growth of non-stoechiometric compounds.

  15. Elm Farm Organic Research Centre December 2006

    OpenAIRE

    Sanders, Richard; Whiltley, Andrew; Haigh, Zoe; Clarke, Sarah; Hitchings, Roger; O'Brien, Josie

    2006-01-01

    The Organic Research Centre. Elm Farm Research Centre Bulletin with Technical Updates from The Organic Advisory Service is a regular publication from The Organic Research Centre. The current issue covers: Report from 2006 Cirencester Conference; Quest for more home produced organic food; in a world where bread matters; Improving wheat with plenty of parents; Unlocking the secrets of the ancient (cereal varieties); Brain food- a good read; Not to late to protect the future: The organic...

  16. Documentation Centre of the Association of African Universities.

    Science.gov (United States)

    Chateh, Peter

    This report presents the results of a study of the Documentation Centre of the Association of African Universities (AAU) undertaken to work out proposals for the rational organization of the Centre, and to explore the possibility of computerizing the Centre and linking it with other centers which provide automated documentation services. The…

  17. Higgs Reconstructed at CERN’s Computer Centre

    CERN Multimedia

    2012-01-01

    Thanks to the enormous computing capacity of the CERN Computer Centre, which hosts about 12,000 servers with 16,000 CPUs (i.e. 64,000 computing cores) and 64,000 hard-disks distributed over 1,100 racks and storing another 22 PB (PetaByte, i.e. 22 million billion bytes) of LHC data during 2011, CERN computing specialists have managed for the first time to reconstruct the “Higgs” (see photo below in which the newly installed racks are highlighted).   In fact, as clear physics evidence of the Higgs is still pending and expected to be established in 2012, the CERN Computer Centre operators have instead rearranged their computer racks in the Computer Centre (Building 513) to spell the word “Higgs”. Bruce Peppa, group leader of the IT/CC group who manages the Computer Centre, said “As many people have noticed, for a few months serious construction work has been going on in the annex to the CERN Computer Centre. With the installation of more servers ...

  18. Centre for urban ecotechnology in ''Oeksnehallen''. [Copenhagen, Denmark

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    The Lord Mayor's Department of the municipality of Copenhagen, Denmark, has with support from this project made a proposal for the establishment of the Centre for Urban Ecotechnology in ''Oeksnehallen'', located in the Vesterbro area of the city. The centre should contribute to the dissemination of knowledge on ecological techniques (regarding passive solar energy etc.) to the inhabitants of Vesterbro and other citizens of Copenhagen, and also serve as a centre in an European context. The ecological demonstration centre will cover an area of two thousand square meters and will also include a cafe, a room for showing coloured slides, facilities for exhibitions created by the center and interested firms etc. The centre should play an important role as part of the ecological concept of urban renewal in Vesterbro. (author).

  19. Purification, molecular cloning and heterologous expression of a glutathione S-transferase involved in insecticide resistance from the rice brown planthopper, Nilaparvata lugens.

    OpenAIRE

    Vontas, John G; Small, Graham J; Nikou, Dimitra C; Ranson, Hilary; Hemingway, Janet

    2002-01-01

    A novel glutathione S-transferase (GST)-based pyrethroid resistance mechanism was recently identified in Nilaparvata lugens [Vontas, Small and Hemingway (2001) Biochem. J. 357, 65-72]. To determine the nature of GSTs involved in conferring this resistance, the GSTs from resistant and susceptible strains of N. lugens were partially purified by anion exchange and affinity chromatography. The majority of peroxidase activity, previously correlated with resistance, was confined to the fraction tha...

  20. Teaching and training programmes in nuclear medicine for medical and paramedical personnel at the Radiation Medicine Centre, Bhabha Atomic Research Centre

    International Nuclear Information System (INIS)

    Sharma, S.M.; Raikar, U.R.

    1986-01-01

    Prior to 1976, the Radiation Medicine Centre had conducted 12 short courses of five weeks' duration on medical uses of radioisotopes. A total of 162 medical and scientific personnel attended the courses from various parts of India. Owing to the rapid advances made in nuclear medicine these courses were becoming inadequate, and in 1973 the Centre introduced one-year full time training courses for doctors and science graduates, peparing them for examinations for the Diploma in Radiation Medicine (DRM) and the Diploma in Medical Radioisotope Techniques (DMRIT) of the University of Bombay. By March 1984, 64 doctors and 53 technologists had obtained the DRM and DMRIT. A recent survey indicated that 70% of the DRM physicians and 68% of the DMRIT technologists are employed in nuclear medicine departments. Besides the formal one-year training courses, the Centre has conducted advanced courses of two weeks' duration on scintigraphy and thyroid function tests. The Radiation Medicine Centre has been the regional reference centre in nuclear medicine for the World Health Organization and International Atomic Energy Agency for more than ten years. The Centre has trained sponsored personnel from other countries of the region. The Centre has also organized seven symposia, workshops and seminars, four of them in collaboration with WHO and one with the IAEA. (author)

  1. Centre for nuclear engineering University of Toronto annual report 1984

    International Nuclear Information System (INIS)

    1984-12-01

    The annual report of the Centre for Nuclear Engineering, University of Toronto covers the following subjects: message from the Dean; Chairman's message; origins of the centre; formation of the centre; new nuclear appointments; and activities of the centre, 1984

  2. Centre of the Cell: Science Comes to Life.

    Science.gov (United States)

    Balkwill, Frances; Chambers, Katie

    2015-01-01

    Centre of the Cell is a unique biomedical science education centre, a widening participation and outreach project in London's East End. This article describes Centre of the Cell's first five years of operation, the evolution of the project in response to audience demand, and the impact of siting a major public engagement project within a research laboratory.

  3. The nuclear research centre at Bariloche, Argentina

    International Nuclear Information System (INIS)

    Abriata, J.P.

    2001-01-01

    The nuclear research centre at Bariloche (CAB) is one of the four centres under the Atomic Energy Commission of Argentina (CNEA). The research programme of CAB addresses various issues like nuclear reactor development, nuclear fuel and fuel cycle, applications of radioisotopes and radiation, and waste management. There is also a basic nuclear science component. The human resource development in the areas of physics and nuclear engineering is done in an associated Balseiro Institute which has undergraduate and graduate programmes as well as doctoral and postdoctoral research. The Centre interacts well with the society and provides services in the nuclear area. It has a close interaction with the nuclear sector of Argentina as also with many international organisations. Regulatory control over the Centre is carried out by the Nuclear Regulatory Authority of Argentina. (author)

  4. Potential of Natural Ventilation in Shopping Centres

    DEFF Research Database (Denmark)

    Diederichsen, Alice; Friis, Kristina; Brohus, Henrik

    2008-01-01

    The indoor environmental quality (IEQ) is a fundamental requirement for a well performing shopping centre. This paper contains a pilot study of the potential of using hybrid ventilation (a combination of automatically controlled natural and mechanical ventilation - respectively NV and MV) in shop......The indoor environmental quality (IEQ) is a fundamental requirement for a well performing shopping centre. This paper contains a pilot study of the potential of using hybrid ventilation (a combination of automatically controlled natural and mechanical ventilation - respectively NV and MV......) in shopping centres with focus on both the achieved IEQ and energy consumptions for air movement. By thermal building simulations it is found that there exists an interesting potential for hybrid ventilation of shopping centres, which can lead to great savings in the electrical energy consumptions...

  5. User-Centred BCI Videogame Design

    OpenAIRE

    Loup-Escande , Emilie; Lotte , Fabien; Loup , Guillaume; Lécuyer , Anatole

    2015-01-01

    International audience; This chapter aims to offer a user-centred methodological framework to guide the design and evaluation of Brain-Computer Interface videogames. This framework is based on the contributions of ergonomics to ensure these games are well suited for their users (i.e., players). It provides methods, criteria and metrics to complete the different phases required by ae human-centred design process. This aims to understand the context of use, specify the user needs and evaluate t...

  6. The Belgian nuclear research centre

    International Nuclear Information System (INIS)

    Moons, F.

    2001-01-01

    The Belgian Nuclear Research Centre is almost exclusively devoted to nuclear R and D and services and is able to generate 50% of its resources (out of 75 million Euro) by contract work and services. The main areas of research include nuclear reactor safety, radioactive waste management, radiation protection and safeguards. The high flux reactor BR2 is extensively used to test fuel and structural materials. PWR-plant BR3 is devoted to the scientific analysis of decommissioning problems. The Centre has a strong programme on the applications of radioisotopes and radiation in medicine and industry. The centre has plans to develop an accelerator driven spallation neutron source for various applications. It has initiated programmes to disseminate correct information on issues of nuclear energy production and non-energy nuclear applications to different target groups. It has strong linkages with the IAEA, OECD-NEA and the Euratom. (author)

  7. Institutional Support : Centre for Research and Technology ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    year-old science and technology research centre at Maseno University in western Kenya. The Centre focuses on science and technology research to influence both national policies and development practices at the community level. Currently ...

  8. Identification of an enhancer element of class Pi glutathione S-transferase gene required for expression by a co-planar polychlorinated biphenyl.

    OpenAIRE

    Matsumoto, M; Imagawa, M; Aoki, Y

    1999-01-01

    3,3',4,4',5-Pentachlorobiphenyl (PenCB), one of the most toxic co-planar polychlorinated biphenyl congeners, specifically induces class Pi glutathione S-transferase (GSTP1) as well as cytochrome P-450 1A1 in primary cultured rat liver parenchymal cells [Aoki, Matsumoto and Suzuki (1993) FEBS Lett. 333, 114-118]. However, the 5'-flanking sequence of the GSTP1 gene does not contain a xenobiotic responsive element, to which arylhydrocarbon receptor binds. Using a chloramphenicol acetyltransferas...

  9. An ethylene-responsive enhancer element is involved in the senescence-related expression of the carnation glutathione-S-transferase (GST1) gene.

    OpenAIRE

    Itzhaki, H; Maxson, J M; Woodson, W R

    1994-01-01

    The increased production of ethylene during carnation petal senescence regulates the transcription of the GST1 gene encoding a subunit of glutathione-S-transferase. We have investigated the molecular basis for this ethylene-responsive transcription by examining the cis elements and trans-acting factors involved in the expression of the GST1 gene. Transient expression assays following delivery of GST1 5' flanking DNA fused to a beta-glucuronidase receptor gene were used to functionally define ...

  10. Waste management in primary healthcare centres of Iran.

    Science.gov (United States)

    Mesdaghinia, Alireza; Naddafi, Kazem; Mahvi, Amir Hossein; Saeedi, Reza

    2009-06-01

    The waste management practices in primary healthcare centres of Iran were investigated in the present study. A total of 120 primary healthcare centres located across the country were selected using the cluster sampling method and the current situation of healthcare waste management was determined through field investigation. The quantities of solid waste and wastewater generation per outpatient were found to be 60 g outpatient(-1) day(-1) and 26 L outpatient(-1) day(-1), respectively. In all of the facilities, sharp objects were separated almost completely, but separation of other types of hazardous healthcare solid waste was only done in 25% of the centres. The separated hazardous solid waste materials were treated by incineration, temporary incineration and open burning methods in 32.5, 8.3 and 42.5% of the healthcare centres, respectively. In 16.7% of the centres the hazardous solid wastes were disposed of without any treatment. These results indicate that the management of waste materials in primary healthcare centres in Iran faced some problems. Staff training and awareness, separation of healthcare solid waste, establishment of the autoclave method for healthcare solid waste treatment and construction of septic tanks and disinfection units in the centres that were without access to a sewer system are the major measures that are suggested for improvement of the waste management practices.

  11. The Manche Storage Centre: 2009 annual report

    International Nuclear Information System (INIS)

    2010-01-01

    After a brief presentation of the ANDRA (the French national agency for the management of radioactive wastes), this report presents the CSM installations (CSM stands for Centre de Stockage de la Manche, the Manche storage centre), recalls results and actions in the field of nuclear safety and in the field of radioprotection. It indicates incidents and accidents which occurred in the installations, presents data about the Centre's releases. It presents the waste management and evokes other pollution. It indicates the various actions undertaken for information transparency

  12. Use of serum gamma glutamyl transferase as a biomarker of stress and metabolic dysfunctions in Rathi cattle of arid tract in India

    Directory of Open Access Journals (Sweden)

    Kataria N.

    2012-08-01

    Full Text Available The investigation was carried out to determine serum gamma glutamyl transferase enzyme as a biomarker of stress and metabolic dysfunctions in Rathi cattle of arid tract in India. Blood samples were collected to harvest serum from healthy male and female, drought affected, ketotic cows, recently aborted cows, cows with diarrhoea, cows with traumatic pericarditis, calves with urinary calculi, cows affected with urea poisoning and cows affected with acidosis. The mean values of γ glutamyl transferase showed significant variations (p≤0.05 according to sex and age in the healthy group of animals. The normal range in healthy animals was from 12 to 34 UL-1. In affected group an average 23.69 times rise in the value was observed from that of healthy group. Cows affected with urea poisoning and acidosis were having highest mean values whereas drought affected animals were having least value. It was concluded that present study attempted to provide a new insight about an old enzyme. As the number of animals in the present study was statistically sufficient therefore the mean value of healthy group can be used as reference value for γ GT in Rathi cattle and other cattle breeds which can help to interpret the variations of serum γ GT in various metabolic diseases of cattle.

  13. Gestion du Centre | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Comité de gestion du Centre (CGC) est composé des membres de la haute direction du CRDI, notamment les directeurs de nos quatre bureaux régionaux et de nos principaux secteurs de programme. Le CGC travaille en collaboration avec le président afin de soutenir la recherche pour le développement, lui fournissant ...

  14. The Role of Parents' Educational Level and Centre Type in Parent Satisfaction with Early Childhood Care Centres: A Study in Greece

    Science.gov (United States)

    Kelesidou, Sofia; Chatzikou, Maria; Tsiamagka, Evmorfia; Koutra, Evangelia; Abakoumkin, Georgios; Tseliou, Eleftheria

    2017-01-01

    This research examines specific facets of parent satisfaction with childcare centres, namely satisfaction with parent-centre communication and the educational services they provide, as well as respective parent beliefs. These were investigated in relation to centre type (private vs public) and parents' education. Parents of different educational…

  15. Addiction research centres and the nurturing of creativity The Norwegian Centre for Addiction Research (SERAF).

    Science.gov (United States)

    Bramness, Jørgen G; Clausen, Thomas; Duckert, Fanny; Ravndal, Edle; Waal, Helge

    2011-08-01

    The Norwegian Centre for Addiction Research (SERAF) at the University of Oslo is a newly established, clinical addiction research centre. It is located at the Oslo University Hospital and has a major focus on opioid dependency, investigating Norwegian opioid maintenance treatment (OMT), with special interest in OMT during pregnancy, mortality, morbidity and criminality before, during and after OMT and alternatives to OMT, such as the use of naltrexone implants. The well-developed health registries of Norway are core assets that also allow the opportunity for other types of substance abuse research. This research includes health services, abuse of prescription drugs and drugs of abuse in connection with traffic. The centre also focuses upon comorbidity, investigating the usefulness and limitations of psychometric instruments, drug abuse in different psychiatric treatment settings and internet-based interventions for hazardous alcohol consumption. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

  16. International Network of Nuclear Reaction Data Centres

    International Nuclear Information System (INIS)

    Otsuka, Naohiko; Dunaeva, Svetlana

    2010-11-01

    The activities of fourteen nuclear data centres are summarized, and their cooperation under the auspices of the International Atomic Energy Agency is described. Each of the centres provides coverage for different geographical zones and/or specific types of nuclear data, thus together providing a complete service for users worldwide. The International Network of Nuclear Reaction Data Centres (NRDC) was established with the objective of providing nuclear physics databases that are required for nuclear technology (encompassing energy and non-energy applications) by coordinating the collection, compilation and dissemination of nuclear data on an international scale. (author)

  17. Japanese maintenance centres strive for greater realism

    International Nuclear Information System (INIS)

    Nedderman, J.

    1987-01-01

    Japanese utilities have devoted considerable efforts to ensuring that realistic plant conditions are simulated at their maintenance centres. In some centres, eg that of Kansai Electric Power Co, realism extends to difficult access, limited lighting and restricted ventilation. (author)

  18. The WHO Collaborating Centre for Research and Control of Schistosomiasis at Niamey, Niger

    Directory of Open Access Journals (Sweden)

    Chippaux J-P

    1997-01-01

    Full Text Available The Centre de Recherche sur les Méningites et les Schistosomes (CERMES is a research institute depending on the Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies - a West African Organization for Public Health - devoted to the studies on schistosomiasis and meningitis. The staff includes 32 persons with 11 scientists and one financial officer. The activities of the CERMES involving schistosomiasis concern three research units: (a ecology of human and animal schistosomiasis transmission; the CERMES defined the different patterns of schistosomiasis transmission in Niger (involving African dry savana; in this field, we have shown, (i the existence of important variability in conditions of transmission of S. haematobium and, (ii natural hybridization between parasitic species of the ruminants (S. bovis and S. curassoni and genetic interaction between human and animal parasites; (b definition of morbidity indicators usable for rapid assessment methods, for appraisal of the severity of the disease and for the evaluation of the efficiency of control methods; we have established the correlation between ultrasonographic data and some cheap and simple field indicators; (c immune response and protective immunity induced by recombinant glutathion S-transferase (Sm28, Sb28 and Sh28 in homologous and heterologous animal models including goats, sheep and non human primates (Erythrocebus patas. In Niger, we participate in all control programs against schistosomiasis to define control strategies, to supervise operations and to participate in their evaluation with external experts. International collaborations constitute a frame including four laboratories in Africa and six laboratories in developed countries (Europe and USA

  19. Phylogenetic characterization of Clonorchis sinensis proteins homologous to the sigma-class glutathione transferase and their differential expression profiles.

    Science.gov (United States)

    Bae, Young-An; Kim, Jeong-Geun; Kong, Yoon

    2016-01-01

    Glutathione transferase (GST) is one of the major antioxidant proteins with diverse supplemental activities including peroxidase, isomerase, and thiol transferase. GSTs are classified into multiple classes on the basis of their primary structures and substrate/inhibitor specificity. However, the evolutionary routes and physiological environments specific to each of the closely related bioactive enzymes remain elusive. The sigma-like GSTs exhibit amino acid conservation patterns similar to the prostaglandin D synthases (PGDSs). In this study, we analyzed the phylogenetic position of the GSTs of the biocarcinogenic liver fluke, Clonorchis sinensis. We also observed induction profile of the GSTs in association with the parasite's maturation and in response to exogenous oxidative stresses, with special attention to sigma-class GSTs and PGDSs. The C. sinensis genome encoded 12 GST protein species, which were separately assigned to cytosolic (two omega-, one zeta-, two mu-, and five sigma-class), mitochondrial (one kappa-class), and microsomal (one membrane-associated proteins in eicosanoid and glutathione metabolism-like protein) GST families. Multiple sigma GST (or PGDS) orthologs were also detected in Opisthorchis viverrini. Other trematode species possessed only a single sigma-like GST gene. A phylogenetic analysis demonstrated that one of the sigma GST lineages duplicated in the common ancestor of trematodes were specifically expanded in the opisthorchiids, but deleted in other trematodes. The induction profiles of these sigma GST genes along with the development and aging of C. sinensis, and against various exogenous chemical stimuli strongly suggest that the paralogous sigma GST genes might be undergone specialized evolution to cope with the diverse hostile biochemical environments within the mammalian hepatobiliary ductal system. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Energy efficiency in U.K. shopping centres

    Science.gov (United States)

    Mangiarotti, Michela

    Energy efficiency in shopping centres means providing comfortable internal environment and services to the occupants with minimum energy use in a cost-effective and environmentally sensitive manner. This research considers the interaction of three factors affecting the energy efficiency of shopping centres: i) performance of the building fabric and services ii) management of the building in terms of operation, control, maintenance and replacement of the building fabric and services, and company's energy policy iii) occupants' expectation for comfort and awareness of energy efficiency. The aim of the investigation is to determine the role of the above factors in the energy consumption and carbon emissions of shopping centres and the scope for reducing this energy usage by changing one or all the three factors. The study also attempts to prioritize the changes in the above factors that are more cost-effective at reducing that energy consumption and identify the benefits and main economic and legal drivers for energy efficiency in shopping centres. To achieve these targets, three case studies have been analysed. Using energy data from bills, the performance of the selected case studies has been assessed to establish trends and current energy consumption and carbon emissions of shopping centres and their related causes. A regression analysis has attempted to break down the energy consumption of the landlords' area by end-use to identify the main sources of energy usage and consequently introduce cost-effective measures for saving energy. A monitoring and occupants' survey in both landlords' and tenants' areas have been carried out at the same time to compare the objective data of the environmental conditions with the subjective impressions of shoppers and shopkeepers. In particular, the monitoring aimed at assessing the internal environment to identify possible causes of discomfort and opportunities for introducing energy saving measures. The survey looked at

  1. Addiction research centres and the nurturing of creativity: National Drug Dependence Treatment Centre, India--a profile.

    Science.gov (United States)

    Ray, Rajat; Dhawan, Anju; Chopra, Anita

    2013-10-01

    The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post-graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre-clinical studies. Capacity-building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  2. An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease.

    Science.gov (United States)

    Wiemels, Richard E; Cech, Stephanie M; Meyer, Nikki M; Burke, Caleb A; Weiss, Andy; Parks, Anastacia R; Shaw, Lindsey N; Carroll, Ronan K

    2017-01-01

    Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus IMPORTANCE: Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently

  3. Interaction of centres on nucleate boiling

    International Nuclear Information System (INIS)

    Chekanov, V.V.

    1977-01-01

    An experimental set-up is described which enables to analyse the growth of a bubble on a heater, the frequency of succession of the bubbles, etc., by the change in the electric signal from a photomultiplier, onto whose photocathode the bubble is projected. The change in the first moments of the statistical distribution of the corresponding parameters (growth time, frequency of succession, and so on) is adopted as the measure of the external effect on the vapour formation centre. It is shown that for single-bubble boiling the greatest effect is exerted by the acoustic waves produced by the bubble in the growth period; during developed boiling one observes mutual suppression of centres spaced at a distance of the order of the detachment diameter. As the heat flux increases, the correlation of the motion of the interface over the heater surface increases as well. When the correlation radius becomes equal to the centre-to-centre distance, the first crisis sets in. It is suggested that heaters with a variable coefficient of temperature conductance along the heat-releasing surface must withstand high subcritical heat fluxes

  4. Proposal for an ecoradiological centre model

    International Nuclear Information System (INIS)

    Perovic, S.M.; Zunic, Z.; Demajo, M.; Konjevic, N.

    1998-01-01

    The problem of establishing an optimal Ecoradiological Centre Model is studied in some detail for the town of Kotor which is under the protection of the World Cultural and Natural Heritage. The proposed structure of the Centre is analyzed from the view of Engineering, Education and Scientific parameters. This Model is suitable for implementation as a network Centre Model for the state of Montenegro. Further, the modelling strategy of the ecoradiological condition control of natural, construction, bio and technological systems is elaborated. The proposal includes the ecoradiological monitoring, radioactive and electromagnetic radiation processing and protection for different natural zones as well as their different geostructures, aerial and hydrogeological conditions. The programme also includes all housing objects (hotels, flats, houses, office premises etc.). Here will also be presented the radiation protection and recommendations for the implementation of Title VII of the European Basic Safety Standards Directive (BSS), concerning significant increase in exposure due to natural radiation sources. Also, the proposal of Local Radiation Protection for the town of Kotor is presented. Our proposal for an Ecoradiological Centre Model presented here is in a form of a pilot programme, applicable also for other towns and states. (author)

  5. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

    DEFF Research Database (Denmark)

    Lira-Navarrete, Erandi; de Las Rivas, Matilde; Compañón, Ismael

    2015-01-01

    the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy......Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present...... and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity...

  6. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  7. Official Centre Hospitality

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sylvain Dufour

    Approved by the Management Executive Committee. - 1 -. Version 3.1.0 effective 2017-06-28. Official Centre Hospitality. 1. Objective. 2. Application. 3. Definitions. 4. Roles and Responsibilities. 5. Authorization. 6. Consultants and Contractors. 7. Reimbursement. 1. Objective. To define the circumstances under which ...

  8. Role of centre vortices in dynamical mass generation

    International Nuclear Information System (INIS)

    Leinweber, Derek B.; Bowman, Patrick O.; Heller, Urs M.; Kusterer, Daniel-Jens; Langfeld, Kurt; Williams, Anthony G.

    2006-01-01

    The mass and renormalization functions of the nonperturbative quark propagator are studied in SU(3) gauge field theory with a Symanzik-improved gluon action and the AsqTad fermion action. Centre vortices in the gauge field are identified by fixing to maximal centre gauge. The role of centre vortices in dynamical mass generation is explored by removing centre vortices from the gauge fields and studying the associated changes in the quark propagator. We find that dynamical mass generation survives in the vortex-removed SU(3) gauge field theory despite the vanishing of the string tension and suppression of the gluon propagator in the infrared suggesting the possibility of decoupling dynamical mass generation from confinement

  9. Reducing cooling energy consumption in data centres and critical facilities

    Science.gov (United States)

    Cross, Gareth

    Given the rise of our everyday reliance on computers in all walks of life, from checking the train times to paying our credit card bills online, the need for computational power is ever increasing. Other than the ever-increasing performance of home Personal Computers (PC's) this reliance has given rise to a new phenomenon in the last 10 years ago. The data centre. Data centres contain vast arrays of IT cabinets loaded with servers that perform millions of computational equations every second. It is these data centres that allow us to continue with our reliance on the internet and the PC. As more and more data centres become necessary due to the increase in computing processing power required for the everyday activities we all take for granted so the energy consumed by these data centres rises. Not only are more and more data centres being constructed daily, but operators are also looking at ways to squeeze more processing from their existing data centres. This in turn leads to greater heat outputs and therefore requires more cooling. Cooling data centres requires a sizeable energy input, indeed to many megawatts per data centre site. Given the large amounts of money dependant on the successful operation of data centres, in particular for data centres operated by financial institutions, the onus is predominantly on ensuring the data centres operate with no technical glitches rather than in an energy conscious fashion. This report aims to investigate the ways and means of reducing energy consumption within data centres without compromising the technology the data centres are designed to house. As well as discussing the individual merits of the technologies and their implementation technical calculations will be undertaken where necessary to determine the levels of energy saving, if any, from each proposal. To enable comparison between each proposal any design calculations within this report will be undertaken against a notional data facility. This data facility will

  10. Australian International Food Security Research Centre | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Australian International Food Security Research Centre. Australian International Food Security Research Centre. http://aciar.gov.au/AIFSC. Cultivate Africa's Future. The Cultivate Africa's Future research partnership is designed to support applied research to combat hunger in sub-Saharan Africa by harnessing the potential ...

  11. Building an applied activation analysis centre

    International Nuclear Information System (INIS)

    Bartosek, J.; Kasparec, I.; Masek, J.

    1972-01-01

    Requirements are defined and all available background material is reported and discussed for the building up of a centre of applied activation analysis in Czechoslovakia. A detailed analysis of potential users and the centre's envisaged availability is also presented as part of the submitted study. A brief economic analysis is annexed. The study covers the situation up to the end of 1972. (J.K.)

  12. Nuclear Power Plant Temelin Technical Support Centre

    International Nuclear Information System (INIS)

    Krizek, K.

    2000-01-01

    The erection of the Technical Support Centre for the Nuclear Power Plant Temelin has been a relatively sophisticated and costly issue. It was by proper use of the existing systems, as e.g. I and C, ISE and other systems, that a robust system has been created that is able to meet any requirements laid on the performance of the Technical Support Centre. The decision of the utility CEZ, a.s. that made it possible to establish the Technical Support Centre at the Nuclear Power Plant Temelin has been a right step which shows the level of safety culture within the utility. (author)

  13. EPR of VHal centres in SrS

    International Nuclear Information System (INIS)

    Seeman, V.; Danilkin, M.; Must, M.; Ots, A.; Paernoja, E.; Pung, L.; Tarkpea, K.

    2006-01-01

    V Hal centres were studied by EPR in SrS doped with halogens after X-raying the samples at 77 K. V Hal centre arises when a hole is captured by sulphide-ion next to a cation vacancy with a halogen ion substituting the opposite sulphide-ion. EPR parameters and thermal decay characteristics are measured for V Cl , V Br , and V I centres. The efficiency of different halogens to produce and stabilise cation vacancies is shown to vary for different alkaline earth sulphides. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  14. Associating science and development - the Trieste Centre

    International Nuclear Information System (INIS)

    Hamende, A.

    1982-01-01

    The International Centre for Theoretical Physics, located in Trieste, Italy, is supported by income from the Italian Government, from UNESCO and from the IAEA. The Centre organizes research sessions, workshops and extended courses on advanced topics in the physical and mathematical sciences and encourages scientists, especially from developing countries, to visit the ICTP for extended periods. With the aim of facilitating the transfer of knowledge to scientists from developing countries, the Centre's current scientific programme is divided up into five major disciplines: physics and energy; physics and frontiers of knowledge; physics and technology; physics and the environment and natural resources; applicable mathematics

  15. Conceptual design and equipment of visitor centres

    International Nuclear Information System (INIS)

    Huettinger, K.

    1993-01-01

    Discussing the needs to be met by a visitor centre, the author develops the strategies to be adopted and defines the items to be included in the information program. The procedure in preparing the layout and design are explained and the media available to provide various levels of information are listed. Principles of selecting and mixing the media are discussed and the functions of the various sections of the centre described. Also included are examples of the costs and time requirements for the establishment of a typical centre. The importance of regular maintenance and updating is emphasized. (author)

  16. Tele-centres as a way of achieving universal access

    DEFF Research Database (Denmark)

    Falch, Morten; Anyimadu, Amos

    2003-01-01

    The success of tele-centres in Ghana is discussed. The tele-centres offer a low cost opportunity to empower local communities in developed and developing countries to meet the challenges of the information society. The tele-centres can also contribute more directly to the supply of non-commercial...

  17. Need and feasibility of telemedicine in non-urban day care centres.

    Science.gov (United States)

    Setia, Monika; DelliFraine, Jami L

    2010-01-01

    There appear to have been no studies of telemedicine in rural day care centres. We have assessed the feasibility of using telemedicine in eight rural day care centres in Pennsylvania, from the day care centres' perspective. The average number of children in these centres was 76 (range 20-150). The centres sent an average of 4.7 children home each month because of illness. Using telephone and face-to-face interviews, we assessed their perceived need for and familiarity with telemedicine, as well as their openness and preparedness for implementing telemedicine. Most day care centres reported a need for telemedicine and were open to learning how to use it. Some centres were concerned about adequate space for the equipment, but overall, the centres felt that their resources were adequate. Telemedicine in rural day care centres appears to be feasible, and would have the potential to save time and money for parents, as well as perhaps improving health care for children in rural areas.

  18. Treatment of effluent at the Saclay Centre d'Etudes Nucleaires (1960); Le traitement des effluents du Centre d'Etudes Nucleaires de Saclay (1960)

    Energy Technology Data Exchange (ETDEWEB)

    Wormser, G [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1960-07-01

    The Centre d'Etudes Nucleaires at Saclay possesses several installations from which liquid radioactive effluent is rejected, and it has thus been found necessary to construct a station for the purification of radioactive liquids and to settle various chemical, analytical and technological problems. This report describes, in the following order: - the disposal possibilities at the Centre d'Etudes Nucleaires, Saclay, - the effluents produced at the centre, - the set-up for collecting effluent, - treatment of the effluent, - results of these treatments. (author) [French] La presence, au Centre d'Etudes Nucleaires de Saclay, de plusieurs installations susceptibles de rejeter des effluents liquides radioactifs a necessite la construction d'une station d'epuration d'eaux radioactives et la mise au point de differents problemes chimiques, analytiques et technologiques. Dans ce rapport, nous exposerons successivement: - les possibilites de rejet du Centre d'Etudes Nucleaires de Saclay, - les effluents du centre, - le dispositif de collecte des effluents, - le traitement de ces effluents, - les resultats de ces traitements. (auteur)

  19. Psycho-oncological care in certified cancer centres--a nationwide analysis in Germany.

    Science.gov (United States)

    Singer, Susanne; Dieng, Sebastian; Wesselmann, Simone

    2013-06-01

    Over the last few years, a nationwide voluntary certification system for cancer centres has been established in Germany. To qualify for certification, cancer centres must provide psycho-oncological care to every patient who needs it. The aim of this study was to find out how many patients have been treated by a psycho-oncologist in the certified centres. All cancer centres in Germany that were re-certified in 2010 provided data documenting how many patients with primary cancer received at least 30 min of psycho-oncological consultation in 2009. Data from n = 456 certified cancer centres were available. In the centres, a total of 36,165 patients were seen by a psycho-oncologist for at least 30 min, representing 37.3% of all patients in the centres. The highest percentage of patients who received psycho-oncological care was found in breast cancer centres (66.7%), and the lowest in prostate cancer centres (6.8%). Half of the patients (50.0%) in gynaecological cancer centres, 37.7% in colon cancer centres and 25.4% in lung cancer centres received psycho-oncological care. Compared with non-certified centres, the proportion of patients receiving psycho-oncological care in certified cancer centres has increased. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Medical applications of accelerators at Tata Memorial Centre

    International Nuclear Information System (INIS)

    Dinshaw, K.A.

    2003-01-01

    The Tata Memorial Centre constitutes the national comprehensive cancer centre for the prevention, diagnosis, treatment and research on cancer. It is well equipped with sophisticated state-of-the-art equipment capable of delivering External Beam Radiotherapy (Ebert) and Brachytherapy. Nearly 400 patients receive Ebert daily at the institute from a team of highly skilled and dedicated radiation oncologists, medical physicists and technologists, making it one of the busiest centres in the country

  1. Occupational deprivation in an asylum centre:

    DEFF Research Database (Denmark)

    Morville, Anne-Le; Erlandsson, Lena-Karin

    2013-01-01

    This article presents a study of three asylum-seeking men from Iran and Afghanistan. It aimed to explore how and if they experienced occupations as occupations in a Danish asylum centre and how their life experience shaped their choice and value of current occupations. In-depth narrative interviews...... explored the participants’ occupational history and its influence on their occupations in the asylum centre. A thematic analysis showed that the participants had been subjected to occupational disruption and deprivation by politically oppressive systems even before their flight. Their occupations...... in Denmark were to a certain extent influenced by their earlier occupations and the current occupational deprivation they all experienced was due to limited possibilities in the centre. Although they tried their best to fill their days and create structure, there was a loss of valued occupations...

  2. Phi Class of Glutathione S-transferase Gene Superfamily Widely Exists in Nonplant Taxonomic Groups.

    Science.gov (United States)

    Munyampundu, Jean-Pierre; Xu, You-Ping; Cai, Xin-Zhong

    2016-01-01

    Glutathione S-transferases (GSTs) constitute a superfamily of enzymes involved in detoxification of noxious compounds and protection against oxidative damage. GST class Phi (GSTF), one of the important classes of plant GSTs, has long been considered as plant specific but was recently found in basidiomycete fungi. However, the range of nonplant taxonomic groups containing GSTFs remains unknown. In this study, the distribution and phylogenetic relationships of nonplant GSTFs were investigated. We identified GSTFs in ascomycete fungi, myxobacteria, and protists Naegleria gruberi and Aureococcus anophagefferens. GSTF occurrence in these bacteria and protists correlated with their genome sizes and habitats. While this link was missing across ascomycetes, the distribution and abundance of GSTFs among ascomycete genomes could be associated with their lifestyles to some extent. Sequence comparison, gene structure, and phylogenetic analyses indicated divergence among nonplant GSTFs, suggesting polyphyletic origins during evolution. Furthermore, in silico prediction of functional partners suggested functional diversification among nonplant GSTFs.

  3. Electrochemical DNA biosensor based on grafting-to mode of terminal deoxynucleoside transferase-mediated extension.

    Science.gov (United States)

    Chen, Jinyuan; Liu, Zhoujie; Peng, Huaping; Zheng, Yanjie; Lin, Zhen; Liu, Ailin; Chen, Wei; Lin, Xinhua

    2017-12-15

    Previously reported electrochemical DNA biosensors based on in-situ polymerization approach reveal that terminal deoxynucleoside transferase (TdTase) has good amplifying performance and promising application in the design of electrochemical DNA biosensor. However, this method, in which the background is significantly affected by the amount of TdTase, suffers from being easy to produce false positive result and poor stability. Herein, we firstly present a novel electrochemical DNA biosensor based on grafting-to mode of TdTase-mediated extension, in which DNA targets are polymerized in homogeneous solution and then hybridized with DNA probes on BSA-based DNA carrier platform. It is surprising to find that the background in the grafting-to mode of TdTase-based electrochemical DNA biosensor have little interference from the employed TdTase. Most importantly, the proposed electrochemical DNA biosensor shows greatly improved detection performance over the in-situ polymerization approach-based electrochemical DNA biosensor. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Optimal catchment area and primary PCI centre volume revisited

    DEFF Research Database (Denmark)

    Schoos, Mikkel Malby; Pedersen, Frants; Holmvang, Lene

    2015-01-01

    AIMS: The currently stated optimal catchment population for a pPCI centre is 300,000-1,100,000, resulting in 200-800 procedures/year. pPCI centres are increasing in number even within small geographic areas. We describe the organisation and quality of care after merging two high-volume centres...

  5. Relation of serum γ-glutamyl transferase activity with copper in an adult population.

    Science.gov (United States)

    Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

    2017-10-26

    The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, pcopper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, pcopper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

  6. Empowerment, patient centred care and self-management.

    Science.gov (United States)

    Pulvirenti, Mariastella; McMillan, John; Lawn, Sharon

    2014-06-01

    Patient or person centred care is widely accepted as the philosophy and practice that underpins quality care. An examination of the Australian National Chronic Disease Strategy and literature in the field highlights assumptions about the self-manager as patient and a focus on clinical settings. This paper considers patient or person centred care in the light of empowerment as it is understood in the health promotion charters first established in Alma Ata in 1977. We argue that patient or person centred care can be reconfigured within a social justice and rights framework and that doing so supports the creation of conditions for well-being in the broader context, one that impacts strongly on individuals. These arguments have broader implications for the practice of patient centred care as it occurs between patient and health professional and for creating shared responsibility for management of the self. It also has implications for those who manage their health outside of the health sector. © 2011 John Wiley & Sons Ltd.

  7. Track detection on the cells exposed to high Linear Energy Transfer heavy-ions by Cr-39 plastic and terminal deoxynucleotidyl transferase(Td T)

    International Nuclear Information System (INIS)

    Mehnati, P.; Keshtkar, A.; Mesbahi, A.; Sasaki, H.

    2006-01-01

    The fatal effect of ionizing radiation on cells depends on Linear Energy Transfer level. The distribution of ionizing radiation is sparse and homogeneous for low Linear Energy Transfer radiations such as X or y, but it is dense and concentrated for high Linear Energy Transfer radiation such as heavy-ions radiation. Materials and Methods: Chinese hamster ovary cells (CHO-K1) were exposed to 4 Gy Fe-ion 2000 keV/μm. The Cr-39 is a special and sensitive plastic used to verify exact position of heavy-ions traversal. Terminal deoxynucleotidyl transferase is an enzyme labeled with [3 H ] d ATP for detection of cellular DNA damage by autoradiography assay. Results: The track of heavy ions traversals presented by pit size was almost similar for all different doses of radiation. No pits to show the track of traversal were found in 20% of the cell nuclei of the irradiation. Apparently these fractions of cells wave not hit by heavy ions. Conclusion: This study indicated the possible usefulness of both the Cr-39 plastics and DNA labeling with Terminal deoxynucleotidyl transferase method for evaluating the biological effect of heavy-ions in comparison with low Linear Energy Transfer ionizing radiation

  8. Fabrication of single optical centres in diamond-a review

    International Nuclear Information System (INIS)

    Orwa, J.O.; Greentree, A.D.; Aharonovich, I.; Alves, A.D.C.; Van Donkelaar, J.; Stacey, A.; Prawer, S.

    2010-01-01

    Colour centres in diamond are rapidly becoming one of the leading platforms for solid-state quantum information processing applications. This is due in large part to the remarkable properties of the nitrogen-vacancy colour centre. From initial demonstrations of room-temperature single photon generation and spin single spin readout and quantum control, diamond nanocrystals are also finding application in magnetometry and biosensing. This review discusses the state of the art in the creation of isolated and small ensembles of optically active diamond defect centres, including nitrogen and nickel-related centres.

  9. Family-Centred Care in Paediatric and Neonatal Nursing- A Literature Review

    Directory of Open Access Journals (Sweden)

    L.K. Irlam

    2002-09-01

    Full Text Available A literature review of family-centred care in paediatric and neonatal nursing was undertaken as part of a research project. This research intended to ascertain the knowledge and attitudes of paediatric and neonatal qualified nurses and nurse educators towards family-centred care as it pertains to infants and children in hospitals in the Gauteng Province. A definition of family-centred care is difficult to formulate mainly due to the lack of consensus about its meaning. Additionally, the diverse societal contexts within which family-centred care is applied further complicate its definition. Internationally in developed countries, family-centred care is viewed as care, which is parent-led in consultation with the nurse practitioner. A family-centred care model for the South African context needs to be developed with the focus on parent participation, a precursor of family-centred care. This article traces the early developments in parental care for hospitalised children with specific reference to the USA, the UK and South Africa. Precursor concepts in family-centred care are described followed by a cursory overview of the reality of family-centred care, its cultural dimensions and matters of family strengths and choices in family-centred care.

  10. Multi-technology control centre to integrate 460 MW renewables

    International Nuclear Information System (INIS)

    2016-01-01

    The new RWE Innogy Aersa Control Centre that has been certified to act as an interface with CECRE (the Renewable Energy Control Centre) since February 2015, connects RWE’s 20 renewable energy facilities with REE, the Spanish Electricity Grid. As a result, it ensures that wind farms, in addition to hydropower and solar plants, can inject the energy generated by its 460 MW installed safely and with no penalties. Green Eagle Solutions, a provider of software solutions for renewable energy companies, has collaborated with RWE in the development of this Control Centre, meeting the high standards of quality and safety required by RWE. This centre uses CompactSCADA® technology to integrate power generation facilities that need to be integrated in a Control Centre to communicate with REE’s CECRE. (Author)

  11. The Future of Leisure Time Centres in Decin

    OpenAIRE

    Hochwalderová, Světluše

    2014-01-01

    This Bachelor thesis deals with the issue of extracurricular education in Decin. The goal of the thesis is to find out whether the conditions for providing extracurricular education in leisure time centres and basic schools can influence the future of leisure time centres. Another goal of the thesis is to map and analyse the offer ot extracurricular activities in leisrue time centres and basic schools. The theoretical part is based on literature, laws, regulations and available resources. The...

  12. The DIY Digital Medical Centre.

    Science.gov (United States)

    Timmis, James Kenneth; Timmis, Kenneth

    2017-09-01

    Healthcare systems worldwide are confronted with major economic, organizational and logistical challenges. Historic evolution of health care has led to significant healthcare sector fragmentation, resulting in systemic inefficiencies and suboptimal resource exploitation. To attain a sustainable healthcare model, fundamental, system-wide improvements that effectively network, and ensure fulfilment of potential synergies between sectors, and include and facilitate coherent strategic planning and organisation of healthcare infrastructure are needed. Critically, they must be specifically designed to sustainably achieve peak performance within the current policy environment for cost-control, and efficiency and quality improvement for service delivery. We propose creation of a new healthcare cluster, to be embedded in existing healthcare systems. It consists of (i) local 24/7 walk-in virtually autonomous do-it-yourself Digital Medical Centres performing routine diagnosis, monitoring, prevention, treatment and standardized documentation and health outcome assessment/reporting, which are online interfaced with (ii) regional 24/7 eClinician Centres providing on-demand clinical supervision/assistance to Digital Medical Centre patients. Both of these are, in turn, online interfaced with (iii) the National Clinical Informatics Centre, which houses the national patient data centre (cloud) and data analysis units that conduct patient- and population-level, personalized and predictive(-medicine) intervention optimization analyses. The National Clinical Informatics Centre also interfaces with biomedical research and prioritizes and accelerates the translation of new discoveries into clinical practice. The associated Health Policy Innovation and Evaluation Centre rapidly integrates new findings with health policy/regulatory discussions. This new cluster would synergistically link all health system components in a circular format, enable not only access by all arms of the health

  13. The negatively charged nitrogen-vacancy centre in diamond: the electronic solution

    International Nuclear Information System (INIS)

    Doherty, M W; Hollenberg, L C L; Manson, N B; Delaney, P

    2011-01-01

    The negatively charged nitrogen-vacancy centre is a unique defect in diamond that possesses properties highly suited to many applications, including quantum information processing, quantum metrology and biolabelling. Although the unique properties of the centre have been extensively documented and utilized, a detailed understanding of the physics of the centre has not yet been achieved. Indeed, there persist a number of points of contention regarding the electronic structure of the centre, such as the ordering of the dark intermediate singlet states. Without a detailed model of the centre's electronic structure, the understanding of the system's unique dynamical properties cannot effectively progress. In this work, the molecular model of the defect centre is fully developed to provide a self-consistent model of the complete electronic structure of the centre. The application of the model to describe the effects of electric, magnetic and strain interactions, as well as the variation of the centre's fine structure with temperature, provides an invaluable tool to those studying the centre and a means of designing future empirical and ab initio studies of this important defect.

  14. Attitude of Farmers towards Kisan Call Centres

    Directory of Open Access Journals (Sweden)

    Shely Mary Koshy

    2017-09-01

    Full Text Available The present study was conducted to measure the attitude of farmers in Kerala, India towards Kisan Call Centre (KCC. Kisan Call Centre provides free agricultural advisory services to every citizen involved in agriculture through a toll free number. One hundred and fifty farmers who have utilized the Kisan Call Centre service were selected from the database of KCC. The results showed that the respondents had moderately favourable attitude towards KCC followed by highly favourable attitude. The variables digital divide, temporal awareness on KCC, satisfaction towards KCC and utilization of KCC were found to have a positive correlation with the attitude of respondents towards KCC.

  15. Nano-engineered pinning centres in YBCO superconducting films

    Energy Technology Data Exchange (ETDEWEB)

    Crisan, A., E-mail: adrian.crisan@infim.ro [National Institute for Materials Physics Bucharest, 105 bis Atomistilor Str., 077125 Magurele (Romania); School of Metallurgy and Materials, University of Birmingham, Edgbaston, B15 2TT Birmingham (United Kingdom); Dang, V.S. [School of Metallurgy and Materials, University of Birmingham, Edgbaston, B15 2TT Birmingham (United Kingdom); Nano and Energy Center, VNU Hanoi University of Science, 334 Nguyen Trai, Thanh Xuan, Hanoi (Viet Nam); Mikheenko, P. [School of Metallurgy and Materials, University of Birmingham, Edgbaston, B15 2TT Birmingham (United Kingdom); Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway)

    2017-02-15

    Highlights: • Power applications of YBCO films/coated conductors in technological relevant magnetic fields requires nano-engineered pinning centre. • Three approaches have been proposed: substrate decoration, quasi-multilayers, and targets with secondary phase nano-inclusions. • Combination of all three approaches greatly increased critical current in YBCO films. • Bulk pinning force, pinning potential, and critical current density are estimated and discussed in relation with the type and strength of pinning centres related to the defects evidenced by Transmission Electron Microscopy. - Abstract: For practical applications of superconducting materials in applied magnetic fields, artificial pinning centres in addition to natural ones are required to oppose the Lorentz force. These pinning centres are actually various types of defects in the superconductor matrix. The pinning centres can be categorised on their dimension (volume, surface or point) and on their character (normal cores or Δκ cores). Different samples have been produced by Pulsed Laser Deposition, with various thicknesses, temperatures and nanostructured additions to the superconducting matrix. They have been characterized by SQUID Magnetic Properties Measurement System and Physical Properties Measurement System, as well as by Transmission Electron Microscopy (TEM). Correlations between pinning architecture, TEM images, and critical currents at various fields and field orientations will be shown for a large number of YBa{sub 2}Cu{sub 3}O{sub x} films with various types and architectures of artificial pinning centres.

  16. The EPFL Plasma Physics Research Centre

    International Nuclear Information System (INIS)

    2001-01-01

    The Plasma Physics Research Centre (CRPP) is a non-departmental unit of the EPFL, and currently employs about 130 people, about 105 on the EPFL site and the rest at the Paul Scherrer Institute, PSI, in Villigen, Switzerland. The CRPP is a National Competence Centre in the field of Plasma Physics. In addition to plasma physics teaching, its missions are primarily the pursuit of scientific research in the field of controlled fusion within the framework of the EURATOM-Swiss Confederation Association and the development of its expertise as well as technology transfer in the field of materials research. As the body responsible for all scientific work on controlled fusion in Switzerland, the CRPP plays a national role of international significance. This document of 6 pages presents the explanation of the Plasma Physics Research Centre' activities (CRPP). (author)

  17. Tax haven or international financial centre? The case of Kenya

    OpenAIRE

    Waris, Attiya

    2014-01-01

    International financial centres are geared to provide optimal conditions for the financial services industry. They encourage activities that can improve a country’s economy, but they may also facilitate money laundering, tax evasion, tax avoidance, and other harmful practices. The Nairobi International Financial Centre and similar centres in Africa can foster development, but also pose significant challenges. Legal and regulatory arrangements determine what types of capital a financial centr...

  18. Historical centres: changing definitions

    Directory of Open Access Journals (Sweden)

    Roberta Lazzarotti

    2014-02-01

    Full Text Available Since the end of the Second World War, the architectural and planning culture has been showing a fluctuating attention to the theme of historical centres and their enhancement. First of all this uneven progress explains the difficulty to reach a homogeneous definition and this is still lacking. During a long phase of this period, the historical parts of the town were considered as objects to be preserved in an integral way, as urban monuments. This is mostly due to the high symbolic value of these settlements, that represent fundamental landmarks. Identity building and empowerment of local communities are indispensable conditions for any development programme, especially in the case of centres or other historic environments at risk of abandonment. The progressive evolution of this concept brings awareness of the impossibility of separating – either in analytical or in planning terms ­ historical centres from their urban and territorial contexts, which are linked by mutual, deep relationships. This article attempts to retrace the steps signaled by the publication of international documents and conventions, from the Charter of Gubbio (1960 to the Charter of Krakow and the European Landscape Convention (2000; they obviously represent particular points of view, not exhaustive of the richness of the positions in the debate, but extremely significant in terms of diffusion and consensus.

  19. Crystalline roof glazing - Westside shopping centre, Berne; Kristalline Dachverglasungen

    Energy Technology Data Exchange (ETDEWEB)

    Enkerli, W.

    2009-07-01

    This illustrated article takes a look at the new shopping and leisure centre on the western outskirts of Berne, Switzerland. In particular, the roof of this unusual building over the motorway with its sloping walls and zig-zag design is looked at. The centre's shopping mall, adventure baths and spa, a multiplex cinema, an old peoples' home and a hotel are briefly discussed, as is the embedding of the centre in its suburban environment. The roof construction with its crystalline skylights is examined and discussed in detail. The centre's building technical services are also briefly commented on.

  20. White-centred retinal haemorrhages (Roth spots).

    OpenAIRE

    Ling, R.; James, B.

    1998-01-01

    Roth spots (white-centred retinal haemorrhages) were classically described as septic emboli lodged in the retina of patients with subacute bacterial endocarditis. Indeed many have considered Roth spots pathognomonic for this condition. More recent histological evidence suggests, however, that they are not foci of bacterial abscess. Instead, they are nonspecific and may be found in many other diseases. A review of the histology and the pathogenesis of these white-centred haemorrhages will be p...

  1. Scheduling participants of Assessment Centres

    DEFF Research Database (Denmark)

    Lysgaard, Jens; Løber, Janni

      Assessment Centres are used as a tool for psychologists and coaches to observe a number of dimensions in a person's behaviour and test his/her potential within a number of chosen focus areas. This is done in an intense course, with a number of different exercises which expose each participant...... Centres usually last two days and involve 3-6 psychologists or trained coaches as assessors. An entire course is composed of a number of rounds, with each round having its individual duration. In each round, the participants are divided into a number of groups with prespecifed pairing of group sizes...

  2. Synergistic and independent actions of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wang

    2015-04-01

    Full Text Available All types of small RNAs in plants, piwi-interacting RNAs (piRNAs in animals and a subset of siRNAs in Drosophila and C. elegans are subject to HEN1 mediated 3' terminal 2'-O-methylation. This modification plays a pivotal role in protecting small RNAs from 3' uridylation, trimming and degradation. In Arabidopsis, HESO1 is a major enzyme that uridylates small RNAs to trigger their degradation. However, U-tail is still present in null hen1 heso1 mutants, suggesting the existence of (an enzymatic activities redundant with HESO1. Here, we report that UTP: RNA uridylyltransferase (URT1 is a functional paralog of HESO1. URT1 interacts with AGO1 and plays a predominant role in miRNA uridylation when HESO1 is absent. Uridylation of miRNA is globally abolished in a hen1 heso1 urt1 triple mutant, accompanied by an extensive increase of 3'-to-5' trimming. In contrast, disruption of URT1 appears not to affect the heterochromatic siRNA uridylation. This indicates the involvement of additional nucleotidyl transferases in the siRNA pathway. Analysis of miRNA tailings in the hen1 heso1 urt1 triple mutant also reveals the existence of previously unknown enzymatic activities that can add non-uridine nucleotides. Importantly, we show HESO1 may also act redundantly with URT1 in miRNA uridylation when HEN1 is fully competent. Taken together, our data not only reveal a synergistic action of HESO1 and URT1 in the 3' uridylation of miRNAs, but also independent activities of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs and an antagonistic relationship between uridylation and trimming. Our results may provide further insight into the mechanisms of small RNA 3' end modification and stability control.

  3. New Cyber Policy Centres for the Global South | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    13 avr. 2018 ... The Cyber Policy Centres initiative was established in 2017 to strengthen independent policy research institutions in sub-Saharan Africa, Asia, and Latin America by providing support and mentorship to build research and policy capacity in the key areas of digital rights, cybersecurity, and innovation policy.

  4. Adjoint administratif (h/f) - Politiques et planification | CRDI - Centre ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    à‑d. les informer au sujet des programmes et des procédures du Centre, des systèmes et des programmes informatiques, organiser des rendez-vous avec des membres clés du personnel du Centre, réacheminer les questions aux personnes-ressources compétentes au Centre, et organiser la création de comptes de ...

  5. The negatively charged nitrogen-vacancy centre in diamond: the electronic solution

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, M W; Hollenberg, L C L [School of Physics, University of Melbourne, Melbourne, Victoria 3010 (Australia); Manson, N B [Laser Physics Centre, Research School of Physics and Engineering, Australian National University, Canberra, Australian Capital Territory 0200 (Australia); Delaney, P, E-mail: marcuswd@unimelb.edu.au [School of Mathematics and Physics, Queen' s University Belfast, Belfast BT7 1NN (United Kingdom)

    2011-02-15

    The negatively charged nitrogen-vacancy centre is a unique defect in diamond that possesses properties highly suited to many applications, including quantum information processing, quantum metrology and biolabelling. Although the unique properties of the centre have been extensively documented and utilized, a detailed understanding of the physics of the centre has not yet been achieved. Indeed, there persist a number of points of contention regarding the electronic structure of the centre, such as the ordering of the dark intermediate singlet states. Without a detailed model of the centre's electronic structure, the understanding of the system's unique dynamical properties cannot effectively progress. In this work, the molecular model of the defect centre is fully developed to provide a self-consistent model of the complete electronic structure of the centre. The application of the model to describe the effects of electric, magnetic and strain interactions, as well as the variation of the centre's fine structure with temperature, provides an invaluable tool to those studying the centre and a means of designing future empirical and ab initio studies of this important defect.

  6. Posttranscriptional modifications in the A-loop of 23S rRNAs from selected archaea and eubacteria.

    Science.gov (United States)

    Hansen, M A; Kirpekar, F; Ritterbusch, W; Vester, B

    2002-02-01

    Posttranscriptional modifications were mapped in helices 90-92 of 23S rRNA from the following phylogenetically diverse organisms: Haloarcula marismortui, Sulfolobus acidocaldarius, Bacillus subtilis, and Bacillus stearothermophilus. Helix 92 is a component of the ribosomal A-site, which contacts the aminoacyl-tRNA during protein synthesis, implying that posttranscriptional modifications in helices 90-92 may be important for ribosome function. RNA fragments were isolated from 23S rRNA by site-directed RNase H digestion. A novel method of mapping modifications by analysis of short, nucleotide-specific, RNase digestion fragments with Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) was utilized. The MALDI-MS data were complemented by two primer extension techniques using reverse transcriptase. One technique utilizes decreasing concentrations of deoxynucleotide triphosphates to map 2'-O-ribose methylations. In the other, the rRNA is chemically modified, followed by mild alkaline hydrolysis to map pseudouridines (psis). A total of 10 posttranscriptionally methylated nucleotides and 6 psis were detected in the five organisms. Eight of the methylated nucleotides and one psi have not been reported previously. The distribution of modified nucleotides and their locations on the surface of the ribosomal peptidyl transferase cleft suggests functional importance.

  7. Origins and Early Evolution of the tRNA Molecule

    Directory of Open Access Journals (Sweden)

    Koji Tamura

    2015-12-01

    Full Text Available Modern transfer RNAs (tRNAs are composed of ~76 nucleotides and play an important role as “adaptor” molecules that mediate the translation of information from messenger RNAs (mRNAs. Many studies suggest that the contemporary full-length tRNA was formed by the ligation of half-sized hairpin-like RNAs. A minihelix (a coaxial stack of the acceptor stem on the T-stem of tRNA can function both in aminoacylation by aminoacyl tRNA synthetases and in peptide bond formation on the ribosome, indicating that it may be a vestige of the ancestral tRNA. The universal CCA-3′ terminus of tRNA is also a typical characteristic of the molecule. “Why CCA?” is the fundamental unanswered question, but several findings give a comprehensive picture of its origin. Here, the origins and early evolution of tRNA are discussed in terms of various perspectives, including nucleotide ligation, chiral selectivity of amino acids, genetic code evolution, and the organization of the ribosomal peptidyl transferase center (PTC. The proto-tRNA molecules may have evolved not only as adaptors but also as contributors to the composition of the ribosome.

  8. Reaction of some macrolide antibiotics with the ribosome. Labeling of the binding site components

    International Nuclear Information System (INIS)

    Tejedor, F.; Ballesta, J.P.

    1986-01-01

    Radioactive carbomycin A, niddamycin, tylosin, and spiramycin, but not erythromycin, can be covalently bound to Escherichia coli ribosomes by incubation at 37 degrees C. The incorporation of radioactivity into the particles is inhibited by SH- and activated double bond containing compounds but not by amino groups, suggesting that the reactions may take place by addition to the double bond present in the reactive antibiotics. This thermic reaction must be different from the photoreaction described for some of these macrolides [Tejedor, F., and Ballesta, J. P. G. (1985) Biochemistry 24, 467-472] since tylosin, which is not photoincorporated, is thermically bound to ribosomes. Most of the radioactivity is incorporated into the ribosomal proteins. Two-dimensional gel electrophoresis of proteins labeled by carbomycin A, niddamycin, and tylosin indicates that about 40% of the radioactivity is bound to protein L27; the rest is distributed among several other proteins such as L8, L2, and S12, to differing extents depending on the drug used. These results indicate, in accordance with previous data, that protein L27 plays an important role in the macrolide binding site, confirming that these drugs bind near the peptidyl transferase center of the ribosome

  9. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis.

    Science.gov (United States)

    Anderson, N M; Li, D; Peng, H L; Laroche, F J F; Mansour, M R; Gjini, E; Aioub, M; Helman, D J; Roderick, J E; Cheng, T; Harrold, I; Samaha, Y; Meng, L; Amsterdam, A; Neuberg, D S; Denton, T T; Sanda, T; Kelliher, M A; Singh, A; Look, A T; Feng, H

    2016-06-01

    Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development. DLST is the E2 transferase of the α-ketoglutarate (α-KG) dehydrogenase complex (KGDHC), which converts α-KG to succinyl-CoA in the TCA cycle. RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of α-KG and a decrease of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy.

  10. Information Centre Radioactivity Switzerland; Beratungsstelle Radioaktivitaet Schweiz

    Energy Technology Data Exchange (ETDEWEB)

    Mosimann, N.; Balsiger, B.; Burger, M. [Bundesamt fuer Bevoelkerungsschutz (Switzerland). LABOR SPIEZ

    2016-07-01

    The Information Centre Radioactivity Switzerland is meant to assess the radiological condition and serves for psychological-medical care of affected members of the Swiss public following an event of increased radioactivity in the environment. The Centre is structured in a modular way consisting of the following modules: ''Entry Measurement'': The visitors are registered and measured for contamination, ''Decontamination'': Contaminated visitors are decontaminated, ''Additional Measurements'': If required, thyroid and whole body measurements are performed, ''Information'': The visitors are informed about radioactivity, radiation protection, the current situation and their individual next steps, ''Exit'': Administrative release from the Information Centre.

  11. Automatic centring and bonding of lenses

    Science.gov (United States)

    Krey, Stefan; Heinisch, J.; Dumitrescu, E.

    2007-05-01

    We present an automatic bonding station which is able to center and bond individual lenses or doublets to a barrel with sub micron centring accuracy. The complete manufacturing cycle includes the glue dispensing and UV curing. During the process the state of centring is continuously controlled by the vision software, and the final result is recorded to a file for process statistics. Simple pass or fail results are displayed to the operator at the end of the process.

  12. The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

    DEFF Research Database (Denmark)

    Gerken, Thomas A; Revoredo, Leslie; Thome, Joseph J C

    2013-01-01

    and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities...... relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides...

  13. F-centre luminescence in nanocrystalline CeO2

    International Nuclear Information System (INIS)

    Aškrabić, S; Dohčević-Mitrović, Z D; Araújo, V D; Ionita, G; De Lima, M M Jr; Cantarero, A

    2013-01-01

    Nanocrystalline CeO 2 powders were synthesized by two cost-effective methods: the self-propagating room temperature (SPRT) method and the precipitation method. Differently prepared samples exhibited different temperature-dependent photoluminescence (PL) in the ultraviolet and visible regions. The PL signals originated from different kinds of oxygen-deficient defect centres with or without trapped electrons (F 0 , F + or F ++ centres). The temperature-dependent PL spectra were measured using different excitation lines, below (457, 488 and 514 nm) or comparable (325 nm) to the ceria optical band gap energy, in order to investigate the positions of intragap localized defect states. Evidence for the presence of F + centres was supported by the signals observed in electron paramagnetic resonance (EPR) measurements. Based on PL and EPR measurements it was shown that F + centres dominate in the CeO 2 sample synthesized by the SPRT method, whereas F 0 centres are the major defects in the CeO 2 sample synthesized by the precipitation method. The luminescence from F ++ states, as shallow trap states, was registered in both samples. Energy level positions of these defect states in the ceria band gap were proposed. (paper)

  14. F-centre luminescence in nanocrystalline CeO2

    Science.gov (United States)

    Aškrabić, S.; Dohčević-Mitrović, Z. D.; Araújo, V. D.; Ionita, G.; de Lima, M. M., Jr.; Cantarero, A.

    2013-12-01

    Nanocrystalline CeO2 powders were synthesized by two cost-effective methods: the self-propagating room temperature (SPRT) method and the precipitation method. Differently prepared samples exhibited different temperature-dependent photoluminescence (PL) in the ultraviolet and visible regions. The PL signals originated from different kinds of oxygen-deficient defect centres with or without trapped electrons (F0, F+ or F++ centres). The temperature-dependent PL spectra were measured using different excitation lines, below (457, 488 and 514 nm) or comparable (325 nm) to the ceria optical band gap energy, in order to investigate the positions of intragap localized defect states. Evidence for the presence of F+ centres was supported by the signals observed in electron paramagnetic resonance (EPR) measurements. Based on PL and EPR measurements it was shown that F+ centres dominate in the CeO2 sample synthesized by the SPRT method, whereas F0 centres are the major defects in the CeO2 sample synthesized by the precipitation method. The luminescence from F++ states, as shallow trap states, was registered in both samples. Energy level positions of these defect states in the ceria band gap were proposed.

  15. The CERN Control Centre is up and running!

    CERN Multimedia

    2006-01-01

    The CERN Control Centre (CCC) that combines all the control rooms for the accelerators, the cryogenic system and the technical infrastructure came into operation on 1st February. This is not a mock-up but the real thing! The CERN Control Centre has been built and put into operation in only 15 months.On 1st February, at 2.00 p.m., Patrick Villeton Pachot started the first Technical Infrastructure shift at the brand new CERN Control Centre. From now on, when you dial 72201 to report a leak or an electrical fault, your call will ring out in the brand new CERN Control Centre. The much anticipated CCC came on line on 1st February, exactly as planned. The 2.00 p.m. shift by the operators of the former Technical Control Room (TCR), now renamed TI for Technical Infrastructure, marked the start of operations at the Centre. The PCR, MCR, TCR and QCR are no more, and all the individual control rooms have been merged into one. And what a control room it is! True to the streamlined image announced when the project was f...

  16. Assessment of ART centres in India: client perspectives.

    Science.gov (United States)

    Sogarwal, Ruchi; Bachani, Damodar

    2009-05-01

    Drug adherence and quality of antiretroviral therapy (ART) services are the keys for the successful ART programme. Hence, an attempt has been made to assess ART centres in India from client perspectives that are receiving services from the centres. Data were gathered through exit interviews with 1366 clients from 27 ART centres that were selected on the basis of drug adherence and client load. Analyses revealed that more than 80 per cent of the clients reported overall satisfaction with the services availed from the centre and 60 per cent reported that the quality of life has improved to a great extent after getting ART. Most of the clients strongly demanded to open ART centre in each district for better access as that will increase drug adherence and eventually control the HIV progression. It has been found that as many as 14% of respondents, ever been on ART, reported non-adherence and 70% of them cited distance and economic factors as the reasons for non-adherence. Study concludes that while majority of the clients were satisfied with ART services, shortage of staff, high level of non-drug adherence, long distances and poor referring system are the weak areas requiring attention.

  17. Rapid health assessments of evacuation centres in areas affected by Typhoon Haiyan

    Directory of Open Access Journals (Sweden)

    Ruth Alma Ramos

    2015-11-01

    Full Text Available Introduction: Typhoon Haiyan caused thousands of deaths and catastrophic destruction, leaving many homeless in Region 8 of the Philippines. A team from the Philippine Field Epidemiology Training Program conducted a rapid health assessment survey of evacuation centres severely affected by Haiyan. Methods: A descriptive study was conducted whereby a convenience sample of evacuation centres were assessed on the number of toilets per evacuee, sanitation, drinking-water, food supply source and medical services. Results: Of the 20 evacuation centres assessed, none had a designated manager. Most were located in schools (70% with the estimated number of evacuees ranging from 15 to 5000 per centre. Only four (20% met the World Health Organization standard for number of toilets per evacuee; none of the large evacuation centres had even half the recommended number of toilets. All of the evacuation centres had available drinking-water. None of the evacuation centres had garbage collection, vector control activities or standby medical teams. Fourteen (70% evacuation centres had onsite vaccination activities for measles, tetanus and polio virus. Many evacuation centres were overcrowded. Conclusion: Evacuation centres are needed in almost every disaster. They should be safely located and equipped with the required amenities. In disaster-prone areas such as the Philippines, schools and community centres should not be designated as evacuation centres unless they are equipped with adequate sanitation services.

  18. Psychiatric rehabilitation in community-based day centres: motivation and satisfaction.

    Science.gov (United States)

    Eklund, Mona; Tjörnstrand, Carina

    2013-11-01

    This study investigated attendees' motivation and motives for participation in day centres and their satisfaction with the rehabilitation, while also addressing the influence of day centre orientation (work- or meeting-place orientation), gender and age. Ninety-three Swedish day centre attendees participated in a cross-sectional study and completed questionnaires about motivation, motives, and satisfaction with the rehabilitation. Data were analysed with non-parametric statistics. The participants were highly motivated for going to the day centre and set clear goals for their rehabilitation. Female gender, but not age, was associated with stronger motivation. The strongest motives for going to the day centre were getting structure to the day and socializing. Attendees at work-oriented day centres more often expressed that they went there to get structure to the day and gain social status. Satisfaction with the rehabilitation was high, and the most common wishes for further opportunities concerned earning money and learning new things. The rehabilitation largely seemed to meet the attendees' needs, but the findings indicated that further developments were desired, such as participation in work on the open market and more work-like occupations in the day centre, accompanied by some kind of remuneration.

  19. Using customer contact centres as relationship marketing instruments

    NARCIS (Netherlands)

    van der Aa, Zanna; Bloemer, Josée; Henseler, Jörg

    2015-01-01

    This article investigates whether, to what extent and how customer contact centres influence customer–firm relationships through customer contact centre quality. The proposed model compiles direct and indirect effects of this form of quality on focal relationship marketing constructs, including

  20. Nuclear research centres - The Egyptian experiment

    International Nuclear Information System (INIS)

    Abdelrazek, I.D.

    2001-01-01

    The Atomic Energy Authority of Egypt has four research centres located at two sites. Its research reactors are devoted to the production of isotopes, neutron beam experiments, activation analysis and materials research. The accelerators are devoted to the production of short lived isotopes for medical applications and materials R and D. Irradiation technology is used for sterilization of medical supplies and food preservation. High level of expertise in those centres is also useful for other developmental activities in Egypt. (author)

  1. Joint Research Centre. Ispra establishment-Italy

    International Nuclear Information System (INIS)

    Angelini, Antonio

    1976-01-01

    A comprehensive review of the work carried out during 1974 and 1975 in the Ispra establishment of the Joint Research Centre is presented. A description of the activity carried out within the context of the running programmes is given. Some of the most relevant scientific and technical achievement are described from the viewpoints of the Scientific Departments of the Centre. The technical and administrative support activities are also presented. A list of publications issued by the Ispra Scientific staff is given

  2. White-centred retinal haemorrhages (Roth spots).

    Science.gov (United States)

    Ling, R; James, B

    1998-10-01

    Roth spots (white-centred retinal haemorrhages) were classically described as septic emboli lodged in the retina of patients with subacute bacterial endocarditis. Indeed many have considered Roth spots pathognomonic for this condition. More recent histological evidence suggests, however, that they are not foci of bacterial abscess. Instead, they are nonspecific and may be found in many other diseases. A review of the histology and the pathogenesis of these white-centred haemorrhages will be provided, along with the work-up of the differential diagnosis.

  3. Family-centred care delivery

    Science.gov (United States)

    Mayo-Bruinsma, Liesha; Hogg, William; Taljaard, Monica; Dahrouge, Simone

    2013-01-01

    Abstract Objective To determine whether models of primary care service delivery differ in their provision of family-centred care (FCC) and to identify practice characteristics associated with FCC. Design Cross-sectional study. Setting Primary care practices in Ontario (ie, 35 salaried community health centres, 35 fee-for-service practices, 32 capitation-based health service organizations, and 35 blended remuneration family health networks) that belong to 4 models of primary care service delivery. Participants A total of 137 practices, 363 providers, and 5144 patients. Main outcome measures Measures of FCC in patient and provider surveys were based on the Primary Care Assessment Tool. Statistical analyses were conducted using linear mixed regression models and generalized estimating equations. Results Patient-reported FCC scores were high and did not vary significantly by primary care model. Larger panel size in a practice was associated with lower odds of patients reporting FCC. Provider-reported FCC scores were significantly higher in community health centres than in family health networks (P = .035). A larger number of nurse practitioners and clinical services on-site were both associated with higher FCC scores, while scores decreased as the number of family physicians in a practice increased and if practices were more rural. Conclusion Based on provider and patient reports, primary care reform strategies that encourage larger practices and more patients per family physician might compromise the provision of FCC, while strategies that encourage multidisciplinary practices and a range of services might increase FCC. PMID:24235195

  4. Terminal deoxynucleotidyl transferase activity in the regenerating thymus of X-irradiated mice

    International Nuclear Information System (INIS)

    Daculsi, R.; Astier, T.; Legrand, E.; Duplan, J.F.

    1982-01-01

    The distribution of terminal deoyxnucleotidyl transferase (TdT) enzyme activity (EU per 10 8 cells) between peaks I and II was followed for a period of 42 days in regenerating thymus of lethally irradiated (9 Gy) C3H mice restored with 10 6 (C3H x AKR) F1 bone marrow cells. The detection of Thy-1.1 and Thy-1.2 surface antigens allowed for the discrimination between host and donor cells, and the main subpopulations of thymic cells were characterized by their sensitivity to H-2sup(k) antiserum and to dexamethazone. Two peaks of TdT activity could be detected on phosphocellulose chromatographic separation. The distribution of TdT activity between these two peaks was followed during the two periods of thymic endo- and exoregeneration. Peak I TdT activity was closely correlated with the variation in the percentage of the high H-2 population. Peak II activity was mostly related to low H-2 cells. The per cell content of both peak I and peak II activities exceeded the norm in rapidly expanding populations. Finally between days 10 and 14 the TdT activity of the endoregenerating population was apparently not different from that of the exoregenerating population between days 14 and 22. (Auth.)

  5. Electrically active sodium-related defect centres in silicon

    DEFF Research Database (Denmark)

    Dahl, Espen; Madsbøll, J.; Søiland, A.-K.

    2013-01-01

    Electrically active defect centres related to sodium in silicon have been examined with deep level transient spectroscopy, and their recombination potential analysed with the microwave photoconductive decay technique. In order to investigate the entire silicon band gap for defect centres, both p-...

  6. SSC RIAR is the largest centre of research reactors

    International Nuclear Information System (INIS)

    Kalygin, V.V.

    1997-01-01

    The State Scientific Centre (SSC) ''Research Institute of Atomic Reactors'' (RIAR) is situated 100 km to the south-east from Moscow, in Dimitrovgrad, the Volga Region of the Russian Federation. SSC RIAR is the largest centre of research reactors in Russia. At present there are 5 types of reactor facilities in operation, including two NPP. One of the main tasks the Centre is the investigations on safety increase for power reactors. Broad international connections are available at the Institute. On the basis of the SSC RIAR during 3 years work has been done on the development of the branch training centre (TC) for the training of operation personnel of research and pilot reactors in Russia. (author). 3 tabs

  7. SSC RIAR is the largest centre of research reactors

    Energy Technology Data Exchange (ETDEWEB)

    Kalygin, V V [State Scientific Centre, Research Inst. of Atomic Reactors (Russian Federation)

    1997-10-01

    The State Scientific Centre (SSC) ``Research Institute of Atomic Reactors`` (RIAR) is situated 100 km to the south-east from Moscow, in Dimitrovgrad, the Volga Region of the Russian Federation. SSC RIAR is the largest centre of research reactors in Russia. At present there are 5 types of reactor facilities in operation, including two NPP. One of the main tasks the Centre is the investigations on safety increase for power reactors. Broad international connections are available at the Institute. On the basis of the SSC RIAR during 3 years work has been done on the development of the branch training centre (TC) for the training of operation personnel of research and pilot reactors in Russia. (author). 3 tabs.

  8. Unified storage systems for distributed Tier-2 centres

    International Nuclear Information System (INIS)

    Cowan, G A; Stewart, G A; Elwell, A

    2008-01-01

    The start of data taking at the Large Hadron Collider will herald a new era in data volumes and distributed processing in particle physics. Data volumes of hundreds of Terabytes will be shipped to Tier-2 centres for analysis by the LHC experiments using the Worldwide LHC Computing Grid (WLCG). In many countries Tier-2 centres are distributed between a number of institutes, e.g., the geographically spread Tier-2s of GridPP in the UK. This presents a number of challenges for experiments to utilise these centres efficaciously, as CPU and storage resources may be subdivided and exposed in smaller units than the experiment would ideally want to work with. In addition, unhelpful mismatches between storage and CPU at the individual centres may be seen, which make efficient exploitation of a Tier-2's resources difficult. One method of addressing this is to unify the storage across a distributed Tier-2, presenting the centres' aggregated storage as a single system. This greatly simplifies data management for the VO, which then can access a greater amount of data across the Tier-2. However, such an approach will lead to scenarios where analysis jobs on one site's batch system must access data hosted on another site. We investigate this situation using the Glasgow and Edinburgh clusters, which are part of the ScotGrid distributed Tier-2. In particular we look at how to mitigate the problems associated with 'distant' data access and discuss the security implications of having LAN access protocols traverse the WAN between centres

  9. The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

    Science.gov (United States)

    Levine, Zebulon G; Walker, Suzanne

    2016-06-02

    O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

  10. Operational experience of UNESCO centres for psychosocial rehabilitation

    International Nuclear Information System (INIS)

    Garnets, O.

    2003-01-01

    Community Centres of social and psychological rehabilitation for the population suffered from Chernobyl catastrophe have been created in Ukraine, Russia and Belarus. Objectives assigned to the Community Centres for psychosocial rehabilitation on the affected population were as follows: improving mental health of all age and social groups in the community; encouraging interactions within the community; empowering community members to take control over their lives; developing social responsibility; promoting problem-solving skills. The Community Centres network has developed psychosocial assistance models relevant to post-catastrophe period (aggravated by social and economic crisis) that might be applied to different types of crises in communities

  11. Characterization of glutathione S-transferase and its immunodiagnostic potential for detecting Taenia multiceps.

    Science.gov (United States)

    Sun, Ying; Wang, Yu; Huang, Xing; Gu, Xiaobing; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

    2017-08-15

    Taenia multiceps is a widespread zoonotic tapeworm parasite which infects cloven-hoofed animals around the world. Animal infection with Coenurus cerebralis, the coenurus larvae of T. multiceps (Tm), is often fatal, which is a major cause of economic losses in stockbreeding. This study amplified the glutathione S-transferase (GST) gene from the total RNA of C. cerebralis. The resulting protein, Tm-GST, consisted of 201 amino acids, and had a predicted molecular mass of 23.1kDa. Its amino acid sequence shares 77.61% similarity with Echinococcus granulosus GST. Recombinant Tm-GST (rTm-GST) was expressed in Escherichia coli. The protein reacted with serum from goats infected with T. multiceps. Immunofluorescence signals indicated that Tm-GST was largely localized in the parenchymatous area of adult T. multiceps; in addition, it was also apparent in the coenurus. An enzyme-linked immunosorbent assay based on rTm-GST showed specificity of 92.8% (13/14) and sensitivity of 90% (18/20) in detecting anti-GST antibodies in serum from naturally infected animals. This study suggests that Tm-GST has the potential to be used as a diagnostic antigen for Coenurosis. Copyright © 2017. Published by Elsevier B.V.

  12. In-vitro effect of flavonoids from Solidago canadensis extract on glutathione S-transferase.

    Science.gov (United States)

    Apáti, Pál; Houghton, Peter J; Kite, Geoffrey; Steventon, Glyn B; Kéry, Agnes

    2006-02-01

    Solidago canadensis is typical of a flavonoid-rich herb and the effect of an aqueous ethanol extract on glutathione-S-transferase (GST) activity using HepG2 cells was compared with those of the flavonol quercetin and its glycosides quercitrin and rutin, found as major constituents. The composition of the extract was determined by HPLC and rutin was found to be the major flavonoidal component of the extract. Total GST activity was assessed using 1-chloro-2,4-dinitrobenzene as a substrate. The glycosides rutin and quercitrin gave dose-dependent increases in GST activity, with a 50% and 24.5% increase at 250 mM, respectively, while the aglycone quercetin inhibited the enzyme by 30% at 250 mM. The total extract of the herb gave an overall dose-dependent increase, the fractions corresponding to the flavonoids showed activating effects while those containing caffeic acid derivatives were inhibitory. The activity observed corresponds to that reported for similar compounds in-vivo using rats, thus the HepG2 cell line could serve as a more satisfactory method of assessing the effects of extracts and compounds on GST.

  13. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    Science.gov (United States)

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-10-11

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

  14. Tests for qualitative treatment-by-centre interaction using a 'pushback' procedure.

    Science.gov (United States)

    Ciminera, J L; Heyse, J F; Nguyen, H H; Tukey, J W

    1993-06-15

    In multicentre clinical trials using a common protocol, the centres are usually regarded as being a fixed factor, thus allowing any treatment-by-centre interaction to be omitted from the error term for the effect of treatment. However, we feel it necessary to use the treatment-by-centre interaction as the error term if there is substantial evidence that the interaction with centres is qualitative instead of quantitative. To make allowance for the estimated uncertainties of the centre means, we propose choosing a reference value (for example, the median of the ordered array of centre means) and converting the individual centre results into standardized deviations from the reference value. The deviations are then reordered, and the results 'pushed back' by amounts appropriate for the corresponding order statistics in a sample from the relevant distribution. The pushed-back standardized deviations are then restored to the original scale. The appearance of opposite signs among the destandardized values for the various centres is then taken as 'substantial evidence' of qualitative interaction. Procedures are presented using, in any combination: (i) Gaussian, or Student's t-distribution; (ii) order-statistic medians or outward 90 per cent points of the corresponding order statistic distributions; (iii) pooling or grouping and pooling the internally estimated standard deviations of the centre means. The use of the least conservative combination--Student's t, outward 90 per cent points, grouping and pooling--is recommended.

  15. Environmental gamma radiation levels around various DAE research centres

    International Nuclear Information System (INIS)

    Takale, R.A.; Swarnakar, M.; Shetty, P.G.; Sahu, S.K.; Pandit, G.G.

    2014-01-01

    This paper presents the gamma radiation levels of four research centres viz. Bhabha Atomic Research Centre (BARC), Trombay; Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam; Variable Energy Cyclotron Centre (VECC), Kolkata; Raja Ramanna Centre for Advanced Technology (RRCAT), Indore; and an industry Board of Radiation and Isotope Technology (BRIT), Vashi. BARC is India's premier nuclear research facility and is a multi-disciplinary research centre with extensive infrastructure for advanced research and development (R and D). IGCAR, Kalpakkam is engaged in scientific research and advanced engineering programme towards the development of Fast Breeder Reactor technology. VECC Kolkata is dedicated to carry out frontier R and D in the fields of Accelerator Science and Technology, Nuclear Science (Theoretical and Experimental), and Material Science etc. RRCAT, Indore has rapidly grown into a premier institute for R and D in lasers, accelerators and their applications. BRIT, Vashi unit is involved in production, development, and supply of radioisotope based products and provision of isotope applications, radiation processing, radio analytical services etc. With an objective to keep a watch on the prevailing environmental background gamma radiation level around all the DAE installations, routine monitoring programme are being carried out using the Thermo Luminescent Dosimeters (TLDs). TLDs provide the simple, inexpensive and precise measurement of small, integrated, external gamma radiation dose rate. The general practice of this programme is to observe the outdoor gamma radiation levels. This paper summarizes the methodology and gamma radiation levels of four research centres viz. BARC, IGCAR, VECC, RRCAT and an industry BRIT, Vashi

  16. The oral food desensitization in the Italian allergy centres.

    Science.gov (United States)

    Meglio, P; Caminiti, L; Pajno, G B; Dello Iacono, I; Tripodi, S; Verga, M C; Martelli, A

    2015-05-01

    Attempts aimed at inducing food tolerance through oral food desensitization (OFD) for the treatment of IgE-mediated food allergies are increasing. In Italy, a number of allergy centres offer this procedure. To collect information on how these centres are organized, how patients are selected, the methods used to administer OFD and how adverse reactions are managed. A questionnaire was e-mailed to all the Italian allergy centres offering OFD. The survey shows a high degree of variability between centres. A correct diagnosis of food allergy is crucial for selecting patients for OFD. In the Italian allergy centres, oral food challenges are mostly open label (84%), but in 16% of cases they are single-blind (8%) or double-blind (8%). A high proportion of allergy centres (83%) offer OFD to children presenting forms of anaphylaxis triggered by traces--or very low doses--of food allergen. The majority of allergy centres (76%) enroll patients over 3 years of age, with 44% enrolling patients above the age of 5. Not-controlled asthma, unreliability of parents in the management of OFD and/or risk of adverse events, are the main reasons for exclusion from the procedure. Although OFD may sometimes be successful and may be considered a valid alternative to an elimination diet, further randomized controlled trials are needed, in order to clarify some controversial points, such as the characteristics of the child undergoing OFD, and the methods of food preparation and administration. Moreover, further studies should further investigate OFD safety, efficacy and costs.

  17. Spatial aspects of planning logistical centres: The case of the economic centre Feniks in the Posavje Region

    Directory of Open Access Journals (Sweden)

    Jure Zavrtanik

    2009-01-01

    Full Text Available Spatial planning of logistics centres follows specific spatial and infrastructural requirements, conditioned by desired traffic flux and scope. Spatial and environmental limitations of the usual freight handling sites are forcing logistical activities to search for areas that can ensure undisturbed expansion and practically unlimited traffic flows. The consequence of this trend is suburbanisation coupled with all the spatial and environmental effects. Within this framework, set against the awareness of the uniqueness of any particular site, the article points out the significance of a comprehensive and timely spatial and environmental planning of logistical centres. Therefore clear spatial objectives, transparent analytical starting blocks and adequate planning regulation prove to be the imperative in the spatial planning of logistical centres and formulation of the spatial concept. Simultaneously, and with respect to the complexity of spatial developments, the significance of territorial cohesion is emphasised, which is manifested as territorial identity, territorial quality and territorial efficiency.

  18. The CSN's Information Centre: a necessary venture

    International Nuclear Information System (INIS)

    Calvo, A.

    1999-01-01

    Every year, around 10,000 pupils will visit the CSN's Information Centre, an exposition area which was created with the intention of explaining simply but strictly, what radiations are, for what they are used, what risks they hold and how they are controlled. Opened in October, 1998, encouraged by Parliamentary urging, the Centre is a path to CSN Information for citizens to use. (Author)

  19. Optimizing Data Centre Energy and Environmental Costs

    Science.gov (United States)

    Aikema, David Hendrik

    Data centres use an estimated 2% of US electrical power which accounts for much of their total cost of ownership. This consumption continues to grow, further straining power grids attempting to integrate more renewable energy. This dissertation focuses on assessing and reducing data centre environmental and financial costs. Emissions of projects undertaken to lower the data centre environmental footprints can be assessed and the emission reduction projects compared using an ISO-14064-2-compliant greenhouse gas reduction protocol outlined herein. I was closely involved with the development of the protocol. Full lifecycle analysis and verifying that projects exceed business-as-usual expectations are addressed, and a test project is described. Consuming power when it is low cost or when renewable energy is available can be used to reduce the financial and environmental costs of computing. Adaptation based on the power price showed 10--50% potential savings in typical cases, and local renewable energy use could be increased by 10--80%. Allowing a fraction of high-priority tasks to proceed unimpeded still allows significant savings. Power grid operators use mechanisms called ancillary services to address variation and system failures, paying organizations to alter power consumption on request. By bidding to offer these services, data centres may be able to lower their energy costs while reducing their environmental impact. If providing contingency reserves which require only infrequent action, savings of up to 12% were seen in simulations. Greater power cost savings are possible for those ceding more control to the power grid operator. Coordinating multiple data centres adds overhead, and altering at which data centre requests are processed based on changes in the financial or environmental costs of power is likely to increase this overhead. Tests of virtual machine migrations showed that in some cases there was no visible increase in power use while in others power use

  20. Institutional Support: Centre for Economic and Social Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Institutional Support: Centre for Economic and Social Research, Education and Documentation (Burkina Faso). The Centre d'études de documentation et de ... innovations to improve lives and livelihoods. Five world-class research teams are working to develop vaccines for neglected livestock diseases in the Global South.

  1. Cooling solutions in an operational data centre: A case study

    International Nuclear Information System (INIS)

    Fakhim, B.; Behnia, M.; Armfield, S.W.; Srinarayana, N.

    2011-01-01

    The rapid growth in data centres - large computing infrastructures containing vast quantities of data processing and storage equipment - has resulted in their consumption of up to 100 times more energy per square metre than office accommodation. The decrease in processing server sizes and the more efficient use of space and server processing are challenging data centre facilities to provide more power and cooling, significantly increasing energy demands. Energy consumption of data centres can be severely and unnecessarily high due to inadequate localised cooling and densely packed server rack layouts. However, as heat dissipation in data centres rises by orders of magnitude, inefficiencies such as air recirculation causing hot spots and flow short-circuiting will have a significant impact on the thermal manageability and energy efficiency of the cooling infrastructure. Therefore, an efficient thermal management of high-powered electronic equipment is a significant challenge for cooling of data centres. To highlight the importance of some of these issues, in this project, an operational data centre has been studied. Field measurements of temperature have been performed. Numerical analysis of flow and temperature fields is conducted in order to evaluate the thermal behaviour of the data centre. A number of undesirable hot spots have been identified. To rectify the problem, a few practical design and remedial solutions to improve the cooling effectiveness have been proposed and examined to allow a reduced air-conditioning power requirement. The findings lead to a better understanding of the cooling issues and the respective proposed solutions allow an improved design for future data centres. - Highlights: → Study of flow and temperature distribution in an operational data centre. → Both field measurements and numerical simulations are conducted. → Numerical simulations are validated by field measurements. → Various modifications to improve the thermal

  2. Politique sociale en Afrique de l'Ouest et du Centre | CRDI - Centre ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Initiative Think tank - Fondation Hewlett. Le CRDI et la Fondation William et Flora Hewlett unissent leurs efforts dans le cadre d'une nouvelle initiative destinée à renforcer les groupes de réflexion et centres de recherche sur les... Voir davantageInitiative Think tank - Fondation Hewlett ...

  3. ATLAS Visitors Centre

    CERN Multimedia

    claudia Marcelloni

    2009-01-01

    ATLAS Visitors Centre has opened its shiny new doors to the public. Officially launched on Monday February 23rd, 2009, the permanent exhibition at Point 1 was conceived as a tour resource for ATLAS guides, and as a way to preserve the public’s opportunity to get a close-up look at the experiment in action when the cavern is sealed.

  4. The storage of nuclear wastes; General problematic of radioactive waste management; The currently operated ANDRA's storage centres in France; The Aube storage centre (CSA) and the industrial centre for gathering, warehousing and storage (Cires); The Cigeo project - Industrial centre of radioactive waste storage in deep geological layers; From R and D to innovation within the ANDRA

    International Nuclear Information System (INIS)

    Abadie, Pierre-Marie; Tallec, Michele; Legee, Frederic; Krieguer, Jean-Marie; Plas, Frederic

    2016-01-01

    This publication proposes a set of four articles which address various aspects related to the storage of nuclear wastes. The authors respectively propose an overview of the general problematic of nuclear waste management, a detailed description of existing storage sites which are currently operated by the ANDRA with a focus on the Aube storage centre or CSA, and on the industrial centre for gathering, warehousing and storage or Cires (The currently operated ANDRA's storage centres in France - The Aube Storage Centre or CSA, and the Industrial Centre for Regrouping, Warehousing and Storage or CIRES), a comprehensive overview of the current status of the Cigeo project which could become one of the most important technological works in France (The Cigeo project - Industrial centre of radioactive waste storage in deep geological layers), and a presentation showing how the ANDRA is involved in R and D activities and innovation (From R and D to innovation within the ANDRA)

  5. Danish Anaesthesia Allergy Centre - preliminary results

    DEFF Research Database (Denmark)

    Garvey, L H; Roed-Petersen, J; Menné, T

    2001-01-01

    BACKGROUND: Anaphylactoid reactions in anaesthesia are rare and should ideally be investigated in specialist centres. At Gentofte University Hospital, we established such a centre in 1998 as a joint venture between the Departments of Anaesthesiology and Dermatology. We present the methodology...... for chlorhexidine. Only one patient has tested positive to a neuromuscular blocking drug (NMBD) so far. DISCUSSION: Our preliminary results appear to differ in two ways from results usually found in this field. Firstly, only one patient has tested positive for a NMBD and secondly, we have had four patients...

  6. Pickering education centre aids nuclear acceptance

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Activities at the new education centre at Pickering are described. The opening of the Nuclear Communications Centre, in 1978, resulting from a search for an effective means of maintaining public acceptance of Ontario Hydro's extensive nuclear power programme. Activities include participation in the interactive computer games, guided tours of educational exhibits including a model of Pickering A generating station, and displays depicting the Candu fuel cycle, outdoor exhibits of renewable energy sources, and tours of the plant. Outside activities include lectures to schools and citizen, business, or professional groups. (U.K.)

  7. Design Considerations for an Intensive Autism Treatment Centre

    Science.gov (United States)

    Deochand, Neil; Conway, Alissa A.; Fuqua, R. Wayne

    2015-01-01

    Individuals with autistic spectrum disorder (ASD) who display severe and challenging behaviour sometimes require centre-based intensive applied behaviour analysis (ABA) therapy to meet their health, safety and educational needs. Unfortunately, despite the need for centre-based treatment, there is a paucity of empirical research on building and…

  8. Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations

    NARCIS (Netherlands)

    Fukao, T.; Mitchell, G. A.; Song, X. Q.; Nakamura, H.; Kassovska-Bratinova, S.; Orii, K. E.; Wraith, J. E.; Besley, G.; Wanders, R. J.; Niezen-Koning, K. E.; Berry, G. T.; Palmieri, M.; Kondo, N.

    2000-01-01

    The activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT; EC 2.8.3.5) is the main determinant of the ketolytic capacity of tissues. Hereditary SCOT deficiency causes episodic ketoacidosis. Here we describe the human SCOT gene, which spans more than 100 kb and contains 17

  9. Person-centred care in nursing documentation.

    LENUS (Irish Health Repository)

    Broderick, Margaret C

    2012-12-07

    BACKGROUND: Documentation is an essential part of nursing. It provides evidence that care has been carried out and contains important information to enhance the quality and continuity of care. Person-centred care (PCC) is an approach to care that is underpinned by mutual respect and the development of a therapeutic relationship between the patient and nurse. It is a core principle in standards for residential care settings for older people and is beneficial for both patients and staff (International Practice Development in Nursing and Healthcare, Chichester, Blackwell, 2008 and The Implementation of a Model of Person-Centred Practice in Older Person Settings, Dublin, Health Service Executive, 2010a). However, the literature suggests a lack of person-centredness within nursing documentation (International Journal of Older People Nursing 2, 2007, 263 and The Implementation of a Model of Person-Centred Practice in Older Person Settings, Dublin, Health Service Executive, 2010a). AIMS AND OBJECTIVES: To explore nursing documentation in long-term care, to determine whether it reflected a person-centred approach to care and to describe aspects of PCC as they appeared in nursing records. METHOD: A qualitative descriptive study using the PCN framework (Person-centred Nursing; Theory and Practice, Oxford, Wiley-Blackwell, 2010) as the context through which nursing assessments and care plans were explored. RESULTS: Findings indicated that many nursing records were incomplete, and information regarding psychosocial aspects of care was infrequent. There was evidence that nurses engaged with residents and worked with their beliefs and values. However, nursing documentation was not completed in consultation with the patient, and there was little to suggest that patients were involved in decisions relating to their care. IMPLICATIONS FOR PRACTICE: The structure of nursing documentation can be a major obstacle to the recording of PCC and appropriate care planning. Documentation

  10. Clarifying the role of mean centring in multicollinearity of interaction effects.

    Science.gov (United States)

    Shieh, Gwowen

    2011-11-01

    Moderated multiple regression (MMR) is frequently employed to analyse interaction effects between continuous predictor variables. The procedure of mean centring is commonly recommended to mitigate the potential threat of multicollinearity between predictor variables and the constructed cross-product term. Also, centring does typically provide more straightforward interpretation of the lower-order terms. This paper attempts to clarify two methodological issues of potential confusion. First, the positive and negative effects of mean centring on multicollinearity diagnostics are explored. It is illustrated that the mean centring method is, depending on the characteristics of the data, capable of either increasing or decreasing various measures of multicollinearity. Second, the exact reason why mean centring does not affect the detection of interaction effects is given. The explication shows the symmetrical influence of mean centring on the corrected sum of squares and variance inflation factor of the product variable while maintaining the equivalence between the two residual sums of squares for the regression of the product term on the two predictor variables. Thus the resulting test statistic remains unchanged regardless of the obvious modification of multicollinearity with mean centring. These findings provide a clear understanding and demonstration on the diverse impact of mean centring in MMR applications. ©2011 The British Psychological Society.

  11. Ordinance on the Finnish Centre of Radiation and Nuclear Safety

    International Nuclear Information System (INIS)

    1990-01-01

    This Ordinance was adopted in implementation of the 1983 Act setting up the Finnish Centre for Radiation and Nuclear Safety and the 1987 Nuclear Energy Act and entered into force on 1 November 1990. The Ordinance specifies the tasks of the Centre, as provided under both Acts, and gives it several supplementary responsibilities. In addition to its overall competence in respect of radiation safety, the Centre will carry out research into and supervise the health effects of radiation and maintain a laboratory for national measurements in that field. The Ordinance also sets out the Centre's organisation chart and the staff duties [fr

  12. TTI Phase 2 Institutional Support: Economic Policy Research Centre ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    TTI Phase 2 Institutional Support: Economic Policy Research Centre ... the Economic Policy Research Centre's (EPRC) role as a credible public policy institution in ... IWRA/IDRC webinar on climate change and adaptive water management.

  13. Training of selected categories of personnel in VUJE branch training centre

    International Nuclear Information System (INIS)

    Jacko, J. et al.

    1983-01-01

    The educational and research activity is described of the training centre which trains personnel for nuclear power plants in Czechoslovakia. Educational work includes training of personnel, the development of instructional and training aids, the assignment of tutors, curriculum development and the organization of final examinations. The results of the centre's educational work for the years 1979 to 1982 are tabulated. The research work of the centre is aimed at improving and increasing the effectiveness of the educational and training process. The spaces and equipment of the centre are described as are personnel conditions, the approach of trainees to education and the attitude of managerial staff to the centre's activities. (J.P.)

  14. Wind energy centre at Gujarat State, India. Business plan

    International Nuclear Information System (INIS)

    Van Hulle, F.; Jansen, J.C.; Prasad, N.S.; Suresh, R.

    1997-07-01

    The report describes the business plan for the establishment of a Wind Energy Centre in Gujarat. This Wind Energy Center has to provide a reliable delivery of a range of development and technical quality assurance services to the wind energy industry in northern India on the basis of sustained operations and recovery of all operating costs and - contingent on the way the Centre is financed - at least part of the initial investment costs. Core activities of the Wind Energy Centre are: Research and development supporting activities for the wind energy sector; Testing and certification of wind energy equipment; Consultancy, monitoring and information services; and Training courses on wind energy technology and implementation. The wind energy centre aims with its services at a number of customers: the manufacturing industry, wind farm developers and governmental authorities. An exploration of the market for the services of the envisaged wind energy centre shows that the concept is financially viable. A set of assumptions has been made about the growth rate of the installed wind power capacity in Northern India and about the number of wind turbine manufacturing companies in the target area of the centre. From these assumptions the total number of new wind turbine types coming on the Indian market annually is derived for a period of ten years. These figures have served as a basis for the determination of the required manpower and facilities of the centre for design and development support activities, feasibility and siting studies, testing and certification. Furthermore a projection has been made for providing expert manpower capacity for carrying out R and D, consultancy and other services. 14 tabs., 1 ref

  15. Family-centred care of children in hospital - a concept analysis

    DEFF Research Database (Denmark)

    Mikkelsen, Gitte; Frederiksen, Kirsten

    2011-01-01

    from 1951 to 2009 resulted in a sample of 25 research articles. Review methods.  A theoretical concept analysis influenced by Risjord's distinction between theoretical and colloquial analyses and based on the principles developed by Morse, Hupcey and Penrod was used to examine the structure...... of professionals and families, mostly represented by mothers. Few attempts have been made to operationalize the concept. Conclusion.  Family-centred care is a partially mature and highly abstract concept. Developing a theory of family-centred care could position the concept in a theoretical context and should also......mikkelsen g. & frederiksen k. (2011) Family-centred care of children in hospital - a concept analysis. Journal of Advanced Nursing67(5), 1152-1162. ABSTRACT: Aim.  This paper reports a concept analysis of family-centred nursing care of hospitalized children. Background.  Family-centred care...

  16. Centre for Political and

    African Journals Online (AJOL)

    user

    and definitions will be published and the data translated into the official ... The Centre provides a terminological and subject-related service to lecturers and ... postgraduate students in international politics, political studies and .... obtain financial contributions (cf. .... making of authoritative and enforceable rules (laws) for.

  17. Implementing Responsibility Centre Budgeting

    Science.gov (United States)

    Vonasek, Joseph

    2011-01-01

    Recently, institutes of higher education (universities) have shown a renewed interest in organisational structures and operating methodologies that generate productivity and innovation; responsibility centre budgeting (RCB) is one such process. This paper describes the underlying principles constituting RCB, its origin and structural elements, and…

  18. The Karlsruhe Nuclear Research Centre is being re-equipped

    International Nuclear Information System (INIS)

    Boehm, H.; Koerting, K.; Huncke, W.; Knapp, W.

    1986-01-01

    The Nuclear Research Centre in Karlsruhe was established over 25 years ago for the express purpose of studying nuclear engineering and its peaceful use. This goal has been achieved - what now. For some time a change has been taking place at the Research Centre: in the direction of man and environmental engineering. 'Bild der Wwissenschaft' has talked to Professor Horst Boehm, the chairman of the Nuclear Centre, about this change and the new areas of research to be concentrated on. (orig.) [de

  19. India | Page 52 | IDRC - International Development Research Centre

    International Development Research Centre (IDRC) Digital Library (Canada)

    Language French. Read more about Startup : Philippine Community eCentres Network. Language English. Read more about Mise sur pied d'un réseau philippin de télécentres communautaires. Language French. Read more about Compétences, gouvernance et nanotechnologies : pleins feux sur l'Inde. Language French.

  20. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling

    International Nuclear Information System (INIS)

    Singhal, Sharad S.; Singh, Sharda P.; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-01-01

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes — higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. - Highlights: • GSTs are the major

  1. A new visitor centre for CMS

    CERN Document Server

    2001-01-01

    At the inauguration of the new CMS visitor centre. The CMS experiment inaugurated a new visitor centre at its Cessy site on 14 June. This will allow the thousands of people who come to CERN each year to follow the construction of one the Laboratory's flagship experiments first-hand. CERN receives over 20,000 visitors each year. Until recently, many of them were taken on a guided tour of one of the LEP experiments. With the closure of LEP, however, trips underground are no longer possible, and the Visits' Service has put in place a number of other itineraries (Bulletin 46/2000). Since the CMS detector will be almost entirely constructed in a surface hall, it is now taking a big share of the limelight. The CMS visitor centre has been built on a platform overlooking CMS construction. It contains a set of clear descriptive posters describing the experiment, along with a video projection showing animations and movies about CMS construction. In the coming weeks, a display of CMS detector elements will be added, as...

  2. The CERN Control Centre is up and running!

    CERN Multimedia

    Maximilien Brice

    2006-01-01

    The CERN Control Centre (CCC) that combines all the control rooms for the accelerators, the cryogenic system and the technical infrastructure came into operation on 1st February. On 1st February, at 2.00 p.m., Patrick Villeton Pachot started the first Technical Infrastructure shift at the brand new CERN Control Centre.

  3. Centre for Educational Technology: The Neglected Basic in ...

    African Journals Online (AJOL)

    In view of the significance of centre for educational technology as the basis for teacher training programme in the colleges of education, precise understanding of the purpose of establishing the centre and its functions needs to be brought to the knowledge of the concern group. Therefore, this paper discusses the functions ...

  4. Aspects of Structure and Dynamics at a Refugee Centre in Denmark

    DEFF Research Database (Denmark)

    Mackrill, Thomas Edward

    1996-01-01

    This article presents an empirical analysis that is part of a practice research project carried out at a Danish Red Cross refugee centre in Copenhagen. It focuses on the relation between the individual refugee and the receiving institution. It points out how the organizational structure...... of a particular refugee centre enables discord between refugees and centre workers as well as among the centre staff. It analyses some of the dynamics of the conflicts that are facilitated by the structure...

  5. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...

  6. Karlsruhe Nuclear Research Centre. Programme budget 1988

    International Nuclear Information System (INIS)

    1987-01-01

    Following a general survey of tasks, planned activities and developmental trends of the nuclear research centre, the report gives an account of the activities to be performed in the subject fields of main interest, showing the budgeting figures for annual expenditure (for personnel, investments, operating costs) up to the year 1991. Further information explains the infrastructure of the centre and the distribution of overall expenditure as well as the budgetary planning. (UA) [de

  7. Proximity to the treating centre and outcomes following subarachnoid hemorrhage.

    Science.gov (United States)

    O'Kelly, Cian J; Spears, Julian; Urbach, David; Wallace, M Christopher

    2011-01-01

    In the management of subarachnoid hemorrhage (SAH), the potential for early complications and the centralization of limited resources often challenge the delivery of timely neurosurgical care. We sought to determine the impact of proximity to the accepting neurosurgical centre on outcomes following aneurysmal SAH. Using administrative data, we analyzed patients undergoing treatment for aneurysmal subarachnoid hemorrhage at neurosurgical centres in Ontario between 1995 and 2004. We compared mortality for patients receiving treatment at a centre in their county (in-county) versus those treated from outside counties (out-of-county). We also examined the impact of distance from the patient's residence to the treating centre. The mortality rates were significantly lower for in-county versus out-of-county patients (23.5% vs. 27.6%, p=0.009). This advantage remained significant after adjusting for potential confounders (HR=0.84, p=0.01). The relationship between distance from the treating centre and mortality was biphasic. Under 300 km, mortality increased with increasing distance. Over 300 km, a survival benefit was observed. Proximity to the treating neurosurgical centre impacts survival after aneurysmal SAH. These results have significant implications for the triage of these critically ill patients.

  8. Colour centre recovery in yttria-stabilised zirconia: photo-induced versus thermal processes

    Science.gov (United States)

    Costantini, Jean-Marc; Touati, Nadia; Binet, Laurent; Lelong, Gérald; Guillaumet, Maxime; Beuneu, François

    2018-05-01

    The photo-annealing of colour centres in yttria-stabilised zirconia (YSZ) was studied by electron paramagnetic resonance spectroscopy upon UV-ray or laser light illumination, and compared to thermal annealing. Stable hole centres (HCs) were produced in as-grown YSZ single crystals by UV-ray irradiation at room temperature (RT). The HCs produced by 200-MeV Au ion irradiation, as well as the F+-type centres (? centres involving oxygen vacancies) were left unchanged upon UV illumination. In contrast, a significant photo-annealing of the latter point defects was achieved in 1.4-MeV electron-irradiated YSZ by 553-nm laser light irradiation at RT. Almost complete photo-bleaching was achieved by laser irradiation inside the absorption band of ? centres centred at a wavelength 550 nm. Thermal annealing of these colour centres was also followed by UV-visible absorption spectroscopy showing full bleaching at 523 K. Colour-centre evolutions by photo-induced and thermally activated processes are discussed on the basis of charge exchange processes between point defects.

  9. Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse - CSNSM/Centre for nuclear and mass spectroscopy, Activity Report 2007-2009

    International Nuclear Information System (INIS)

    2010-01-01

    The Centre for nuclear and mass spectroscopy (CSNSM) is a CNRS (National Centre for Scientific Research) laboratory affiliated with Paris-Sud University. The CSNSM is involved in pluri-disciplinary activities covering various scientific domains: Nuclear Structure (SNO), Nuclear Astrophysics (AN), Solid State Astrophysics (AS), Solid State Physics (PS) and Chemical Physics of Irradiation. This document presents the activity of the Centre during the 2007-2009 years: Nuclear Astrophysics; Solid State Astrophysics; Physics and Chemistry of Irradiation; Solid State Physics and cryogenic detectors; Solid State Physics, Condensed Matter and Irradiation; Structure of the Atomic Nucleus; Teaching and training activities; Spreading scientific culture; Administrative services; Electronics Group; Computer Department; Mechanics Department; RESET Service (Radiation-Environment-Safety- Maintenance-Work); SEMIRAMIS (ion source and ion beam handling)

  10. Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse - CSNSM/Centre for nuclear and mass spectroscopy, Activity Report 2010-2012

    International Nuclear Information System (INIS)

    2013-07-01

    The Centre for nuclear and mass spectroscopy (CSNSM) is a CNRS (National Centre for Scientific Research) laboratory affiliated with Paris-Sud University. The CSNSM is involved in pluri-disciplinary activities covering various scientific domains: Nuclear Structure (SNO), Nuclear Astrophysics (AN), Solid State Astrophysics (AS), Solid State Physics (PS) and Chemical Physics of Irradiation. This document presents the activity of the Centre during the 2010-2012 years: Nuclear Astrophysics; Solid State Astrophysics; Physics and Chemistry of Irradiation; Solid State Physics Group; Condensed Matter and Irradiation: from fundamental to functional; Structure of the Atomic Nucleus; Teaching activities; Spreading scientific culture; Administrative services; Electronics Group; Computer Department; Mechanics Department; RESET Service (Radiation-Environment-Safety- Maintenance-Work); SEMIRAMIS (ion source and ion beam handling)

  11. Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse - CSNSM/Centre for nuclear and mass spectroscopy, Activity Report 1992-1994

    International Nuclear Information System (INIS)

    2003-01-01

    The Centre for nuclear and mass spectroscopy (CSNSM) is a CNRS (National Centre for Scientific Research) laboratory affiliated with Paris-Sud University. The CSNSM is involved in pluri-disciplinary activities covering various scientific domains: Nuclear Structure (SNO), Nuclear Astrophysics (AN), Solid State Astrophysics (AS), Solid State Physics (PS) and Chemical Physics of Irradiation. This document presents the activity of the Centre during the 1992-1994 years: 1 - Nuclear structure; 2 - Nuclear astrophysics; 3 - Basic symmetries; 4 - Accelerator-based mass spectroscopy; 5 - Solid State Astrophysics; 6 - Physics and Chemistry of Irradiation; 7 - Solid State Physics; 8 - SEMIRAMIS (ion source and ion beam handling); 9 - Computer Department; 10 - Electronics Group; 11 - Mechanics Department; 12 - Permanent training; 13 - Health and safety; 14 - Seminars; 15 - Dissertations; 16 - Publications; 17 - Staff

  12. A SERS protocol as a potential tool to access 6-mercaptopurine release accelerated by glutathione-S-transferase.

    Science.gov (United States)

    Wang, Ying; Sun, Jie; Yang, Qingran; Lu, Wenbo; Li, Yan; Dong, Jian; Qian, Weiping

    2015-11-21

    The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.

  13. The identification and characterisation of a functional interaction between arginyl-tRNA-protein transferase and topoisomerase II

    International Nuclear Information System (INIS)

    Barker, Catherine R.; Mouchel, Nathalie A.P.; Jenkins, John R.

    2006-01-01

    Topoisomerase II is required for the viability of all eukaryotic cells. It plays important roles in DNA replication, recombination, chromosome segregation, and the maintenance of the nuclear scaffold. Proteins that interact with and regulate this essential enzyme are of great interest. To investigate the role of proteins interacting with the N-terminal domain of the Saccharomyces cerevisiae topoisomerase II, we used a yeast two-hybrid protein interaction screen. We identified an interaction between arginyl-tRNA-protein transferase (Ate1) and the N-terminal domain of the S. cerevisiae topoisomerase II, including the potential site of interaction. Ate1 is a component of the N-end rule protein degradation pathway which targets proteins for degradation. We also propose a previously unidentified role for Ate1 in modulating the level of topoisomerase II through the cell cycle

  14. The Application of Computer Systems Used in Logistics Centres by Courier Companies

    Directory of Open Access Journals (Sweden)

    Tomasz Szczepanik

    2017-06-01

    Full Text Available In the era of pervasive computerization, the need for rapid and uninterrupted transmission and receiving information handling systems is an essential component of business operations. The use of information technology to use the full capabilities of systems supporting the implementation of the basic processes in the logistics centres ensures proper implementation of tasks. Hence, courier companies cooperating with logistic centres have the opportunity to use the information systems used in logistics centres for the execution of the courier business. The purpose of this article is to identify the impact of information systems used in logistics centres for courier companies services. The article presents a class of information systems used in logistics centres and the number of systems used by courier companies. Characterized the impact of information systems to improve the operation of logistics centres and assesses the extent to which the use of the information system of logistics centres affects the information flow in courier companies. The study showed that the use of the IT systems offered by the logistics centres streamlines the efficiency of information flow in the courier service. Research has shown which IT systems logistics centres are use and how their use by courier companies affects the information flow in courier services.

  15. Community Documentation Centre on Industrial Risk. Bulletin no. 8

    International Nuclear Information System (INIS)

    Masera, M.; Rasmussen, K.

    1993-01-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  16. Community Documentation Centre on Industrial Risk. Bulletin no. 4

    International Nuclear Information System (INIS)

    Gow, H.B.F.

    1991-01-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  17. Community Documentation Centre on Industrial Risk. Bulletin no. 10

    International Nuclear Information System (INIS)

    Perschke, A.; Kirchsteiger, C.

    1996-01-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  18. Community Documentation Centre on Industrial Risk. Bulletin no. 5

    International Nuclear Information System (INIS)

    Gow, H.B.F.

    1991-11-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  19. Community Documentation Centre on Industrial Risk. Bulletin no. 7

    International Nuclear Information System (INIS)

    Gow, H.B.F.; Carditello, I.

    1993-04-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  20. Community Documentation Centre on Industrial Risk. Bulletin no. 9

    International Nuclear Information System (INIS)

    Perschke, A.

    1995-01-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  1. Community Documentation Centre on Industrial Risk. Bulletin no. 6

    International Nuclear Information System (INIS)

    Gow, H.B.F.

    1992-06-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  2. Community Documentation Centre on Industrial Risk. Bulletin no. 11

    International Nuclear Information System (INIS)

    Perschke, A.; Kirchsteiger, C.; Carnevali, C.

    1997-01-01

    The Directorate-General for Environment, Nuclear Safety and Civil Protection of the Commission of the European Communities is responsible for the effective and harmonized implementation of the Directive 82/501/EEC on the major-accident hazards of certain industrial activities. To this end, the Commission, in collaboration with the Committee of Competent Authorities responsible for the implementation of this Directive in the twelve Member States, carries out a whole range of activities. One of the most essential areas for action identified was the need for a systematic diffusion of information concerning the practical implementation of the Directive in the Member States, including the technical rules and guidelines applied, the safety practices and the lessons learnt from major accidents. Therefore, the Commission decided to set up a Community Documentation Centre on Industrial Risks (CDCIR). This Documentation Centre is run by the European Commission, Joint Research Centre, Institute for Systems Engineering and Informatics (ISEI), at Ispra, Italy, among its support activities on the implementation of the Directive. The Documentation Centre will collect, classify and review technical rules, guidelines and documents concerning the requirements of the Directive, as well as the safety of industrial installations produced by governments, administrative, scientific or technical bodies, national or international organizations and industrial or professional associations. Documents on major accidents in the form of reports, videotapes will also be collected and reviewed. The Centre is accessible to interested visitors, documents which are not covered by copyright and are not restricted can be obtained from the Documentation Centre on request. Periodical volumes which will feature the inventory, including abstracts, of the collected material will be published and made available to all interested parties. The Centre will also publish documents devoted to compare existing

  3. Review of CERN Computer Centre Infrastructure

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The CERN Computer Centre is reviewing strategies for optimizing the use of the existing infrastructure in the future, and in the likely scenario that any extension will be remote from CERN, and in the light of the way other large facilities are today being operated. Over the past six months, CERN has been investigating modern and widely-used tools and procedures used for virtualisation, clouds and fabric management in order to reduce operational effort, increase agility and support unattended remote computer centres. This presentation will give the details on the project’s motivations, current status and areas for future investigation.

  4. Methods in Mapping Usability of Malaysia’s Shopping Centre

    Directory of Open Access Journals (Sweden)

    Abdul Ghani Aida Affina

    2016-01-01

    Full Text Available With more than 200 number of shopping centre in Klang Valley itself, we the consumer actually have vast of choices. Instead of the machineries varieties from the lower class product till the posh one, each of those shopping centres eventually offers the typical product same as others. Those shopping centers are competing with each other and in great endeavour to attract more consumers, to visit and spend. As for the visitor, the typical product and boring ambience seems similar in all malls, and is looking something beyond the standard. Something that promising quality embedded in shopping centre which evokes the various emotions of the user along their journey in malls. This quality is known as usability. Usability; as defined generally is a global user’s experience response with product, environment, service or facilities. It is an assessment in extracting the qualities of shopping centre design. In mapping it, there are a few synthesizing methods to implement it. Therefore, this paper purposely to review the method that been used in usability of Malaysia’s shopping centre research with a few references on previous research done in usability assessment by predecessor’s scholars. With the accentuation on three elements that anchoring what the usability is: effectiveness, efficient and satisfaction, it is hope that this overview can lead other researcher in portraying its relationship with the quality and ‘user friendly’ design of shopping centre.

  5. Culture managers education: system dynamics model of the coworking design centre

    OpenAIRE

    Šviráková, Eva; Soukalová, Radomila; Bednář, Pavel; Danko, Lukáš

    2014-01-01

    Coworking Centre is a concept of joint use of space by individuals working in related spheres that seek their chance in the labour market as freelancers. The strategy for the development of creative region mentions coworking centres as one of its tools. This article aims to create a business model of the Coworking Design Centre. By simulating a coworking centre model we are increasing knowledge of the culture managers about this type of business. We have introduced teaching business using the...

  6. Wind energy centre at Mithapur, Gujarat, India. Technical report

    International Nuclear Information System (INIS)

    Van Hulle, F.; Van der Borg, N.; Prasad, N.S.; Suresh, R.; Rajsekhar, B.

    1997-07-01

    The report describes the design and set-up of a Wind Energy Centre in Gujarat. This Wind Energy Centre has to provide a reliable delivery of a range of development and technical quality assurance services to the wind energy industry in northern India. Infrastructural and organizational requirements of the centre have been defined as per the demands expressed by the industry. This include, site and land, building, equipment - hardware/software, manpower, etc. A suitable site has been identified on the western coast of Gujarat (in the vicinity of Mithapur). Based on the feedback from the industry and keeping in mind the possibilities and state-of-the-art followed in intemationally accepted centres, a range of activities including research and development, support to indigenisation, testing and certification, as well as training have been addressed. Facilities include the following: (1) Test site: test pads, building, roads, power collection system, meteo-towers etc; (2) Mobile test equipment: basic measurement sets, transportable meteo-towers, auxiliary equipment; and (3) Blade test facility: building, foundation, loading and measuring facilities. At full capacity the centre will employ approximately 20 people. 3 figs., 4 tabs

  7. Victims' use of professional services in a Dutch sexual assault centre

    NARCIS (Netherlands)

    Bicanic, I.; Snetselaar, H.; de Jongh, A.; van de Putte, E.

    2014-01-01

    Background: Prior research endorsed the establishment of sexual assault centres in the Netherlands because of the potential benefit for victims’ mental recovery. In 2012, the first Dutch sexual assault centre was founded at the University Medical Center Utrecht. The aim of the centre is to provide

  8. Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

    Directory of Open Access Journals (Sweden)

    Michela Pasello

    2011-01-01

    Full Text Available Recent studies have indicated that targeting glutathione-S-transferase (GST isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthiohexanol (NBDHEX has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST. NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

  9. IAEA To Launch Centre On Ocean Acidification

    International Nuclear Information System (INIS)

    2012-01-01

    Full text: The International Atomic Energy Agency (IAEA) is to launch a new centre this summer to address the growing problem of ocean acidification. Operated by the Agency's Monaco Environmental Laboratories, the Ocean Acidification International Coordination Centre will serve the scientific community - as well as policymakers, universities, media and the general public - by facilitating, promoting and communicating global actions on ocean acidification. Growing amounts of carbon dioxide in the Earth's atmosphere are being absorbed in the planet's oceans which increases their acidity. According to the experts, ocean acidification may render most regions of the ocean inhospitable to coral reefs by 2050 if atmospheric carbon dioxide levels continue to increase. This could lead to substantial changes in commercial fish stocks, threatening food security for millions of people as well as the multi-billion dollar fishing industry. International scientists have been studying the effect and possible responses, and the new centre will help coordinate their efforts. ''During the past five years, numerous multinational and national research projects on ocean acidification have emerged and significant research advances have been made,'' said Daud bin Mohamad, IAEA Deputy Director General for Nuclear Sciences and Applications. ''The time is now ripe to provide international coordination to gain the greatest value from national efforts and research investments.'' The centre will be supported by several IAEA Member States and through the Peaceful Uses Initiative, and it will be overseen by an Advisory Board consisting of leading institutions, including the U.N. Intergovernmental Oceanographic Commission, the U.S. National Oceanic and Atmospheric Administration, the U.N. Food and Agriculture Organization, the Fondation Prince Albert II de Monaco, the OA-Reference User Group, as well as leading scientists and economists in the field. The new centre will focus on international

  10. Development of the Advanced CANDU Reactor control centre

    International Nuclear Information System (INIS)

    Malcolm, S.; Leger, R.

    2004-01-01

    The next generation CANDU control centre is being designed for the Advanced CANDU Reactor (ACR) station. The design is based upon the recent Qinshan control room with further upgrades to meet customer needs with respect to high capacity factor with low Operation, Maintenance and Administration (OM and A) costs. This evolutionary design includes the long proven functionality at several existing CANDU control centres such as the 4-unit station at Darlington, with advanced features made possible by new control and display technology. Additionally, ACR control centres address characteristics resulting from Human Factors Engineering (HFE) analysis of control centre operations in order to further enhance personnel awareness of system and plant status. Statistics show that up to 70% of plant significant events, which have caused plant outages, have a root cause attributable to the human from such sources as complex interfaces, procedures, maintenance and management practices. Consequently, special attention is made for the application of HFE throughout the ACR design process. The design process follows a systematic analytical approach to define operations staff information and information presentation requirements. The resultant human-system interfaces (HSI) such as those for monitoring, annunciation and control information are then verified and validated against the system design requirements to provide a high confidence level that adequate and correct information is being provided in a timely manner to support the necessary operational tasks. The ACR control centre provides plant staff with an improved operability capability due to the combination of systematic design and enhanced operating features. Significant design processes (i.e. development) or design features which contribute to this improved operability, include: Design Process: Project HFE Program Plan - intent, scope, timeliness and interfacing; HFE aspects of design process - procedures and instructions

  11. Development of the advanced CANDU reactor control centre

    International Nuclear Information System (INIS)

    Malcolm, S.; Leger, R.

    2004-01-01

    The next generation CANDU control centre is being designed for the Advanced CANDU Reactor (ACR) station. The design is based upon the recent Qinshan control room with further upgrades to meet customer needs with respect to high capacity factor with low Operation, Maintenance and Administration (OM and A) costs. This evolutionary design includes the long proven functionality at several existing CANDU control centres such as the 4-unit station at Darlington, with advanced features made possible by new control and display technology. Additionally, ACR control centres address characteristics resulting from Human Factors Engineering (HFE) analysis of control centre operations in order to further enhance personnel awareness of system and plant status. Statistics show that up to 70% of plant significant events, which have caused plant outages, have a root cause attributable to the human from such sources as complex interfaces, procedures, maintenance and management practices. Consequently, special attention is made for the application of HFE throughout the ACR design process. The design process follows a systematic analytical approach to define operations staff information and information presentation requirements. The resultant human-system interfaces (HSI) such as those for monitoring, annunciation and control information are then verified and validated against the system design requirements to provide a high confidence level that adequate and correct information is being provided in a timely manner to support the necessary operational tasks. The ACR control centre provides plant staff with an improved operability capability due to the combination of systematic design and enhanced operating features. Significant design processes (i.e. development) or design features which contribute to this improved operability, include: Design Process: Project HFE Program Plan - intent, scope, timeliness and interfacing; HFE aspects of design process - procedures and instructions

  12. Do flow principles of operations management apply to computing centres?

    CERN Document Server

    Abaunza, Felipe; Hameri, Ari-Pekka; Niemi, Tapio

    2014-01-01

    By analysing large data-sets on jobs processed in major computing centres, we study how operations management principles apply to these modern day processing plants. We show that Little’s Law on long-term performance averages holds to computing centres, i.e. work-in-progress equals throughput rate multiplied by process lead time. Contrary to traditional manufacturing principles, the law of variation does not hold to computing centres, as the more variation in job lead times the better the throughput and utilisation of the system. We also show that as the utilisation of the system increases lead times and work-in-progress increase, which complies with traditional manufacturing. In comparison with current computing centre operations these results imply that better allocation of jobs could increase throughput and utilisation, while less computing resources are needed, thus increasing the overall efficiency of the centre. From a theoretical point of view, in a system with close to zero set-up times, as in the c...

  13. Yeast one-hybrid system used to identify the binding proteins for rat glutathione S-transferase P enhancer I.

    Science.gov (United States)

    Liao, Ming-Xiang; Liu, Dong-Yuan; Zuo, Jin; Fang, Fu-De

    2002-03-01

    To detect the trans-factors specifically binding to the strong enhancer element (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. Yeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library to identify potential trans-factors that can interact with core sequence of GPEI(cGPEI). Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of transfactors to cGPEI. cDNA fragments coding for the C-terminal part of the transcription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. The binding of c-Jun and ANT to GPEI core sequence were confirmed. Rat c-jun transcriptional factor and ANT may interact with cGPEI. They could play an important role in the induced expression of GST-P gene.

  14. Intermodal Logistics Centres and Freight Corridors – Concepts and Trends

    Directory of Open Access Journals (Sweden)

    Norbert Wagener

    2017-09-01

    Full Text Available . Background: The development of international freight corridors, as the Trans European Network and new rail and inland shipping corridors in Asia and Africa, require efficient logistics centres along these corridors which serve as intermodal interfaces and provide a variety of different logistics service functions. The definition of the term logistics centre differs between countries and implies different functionalities. Locations are often selected randomly and business models are opportunity driven, especially in highly dynamic and less regulated new emerging economies. In particular Freight Villages as a special form of logistics centres have a high impact on regional development and serve as cargo generator for freight corridors. Consideration of general principles how to establish Freight Villages could improve the effectiveness of these logistics centres along freight corridors. Methods: Based on a literature review a comprehensive and hierarchical definition of logistics centres will be discussed and applied. From experiences in the development of logistics centres in several countries, especially in Germany and Lithuania, challenges and concepts concerning regulatory framework, determination of location and business and financing models are discussed. Results: Concerning the definition of logistics centres a hierarchical definition is applied which comprises different levels of logistics centres depending on the scope of the value adding and the functionality. As general principles for the development of Freight Villages the active role of the state, master planning, objective location finding, participation and co-operation of different stakeholders in the business model and a stepwise scheme for financing are introduced. Major trends for the future development of Freight Villages are the digitalization of supply chains, the application of new intermodal technologies and of innovative telematics systems, solutions for low emission and

  15. Atomic energy training centres in Latin America. Report of IAEA Mission

    International Nuclear Information System (INIS)

    1959-01-01

    In January 1958, the Brazilian representative on the Board of Governors of the International Atomic Energy Agency - supported by the Governors from Argentina and Guatemala - proposed that a study should be made of the possibility of setting up one or more atomic energy training centres in Latin America. Countries now having facilities that could be used for co-operative training are Argentina, where rapid strides are being made in building up an integrated atomic energy centre in the Buenos Aires; Brazil, which has successfully established a physical science nuclear laboratory and a radio-biology centre; Venezuela, with a medico-biological centre from which much may be expected; and Mexico, where nuclear science courses are to be provided by the University of Mexico. The report discusses two alternatives for the establishment of training centres: 'specialized centres' or 'integrated centres' and concludes that the integrated centre is the preferable one however specialized centres stand a much higher chance of being staffed successfully. They are inherently smaller and consequently costs for facilities and equipment are much less. In addition use might be made of existing facilities. It is stated that one of the specialized atomic energy training centres to be established might well be in the field of radio-botany. Agriculture is a major source of income throughout Latin America. There are many agricultural schools and experimental stations throughout the region and also the Inter-American Institute of Agricultural Science at Turrialba, Costa Rica. The authors of the report concluded that a training centre in radio-botany should provide vitally needed knowledge and vitally needed specialists to all the agricultural installations in Latin America. The report recommends that (1) the Agency should meet the requests of Latin American universities by, for example, supplying equipment and sending experts; (2) at least one specialized training centre should be established

  16. Atomic energy training centres in Latin America. Report of IAEA Mission

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1959-01-15

    In January 1958, the Brazilian representative on the Board of Governors of the International Atomic Energy Agency - supported by the Governors from Argentina and Guatemala - proposed that a study should be made of the possibility of setting up one or more atomic energy training centres in Latin America. Countries now having facilities that could be used for co-operative training are Argentina, where rapid strides are being made in building up an integrated atomic energy centre in the Buenos Aires; Brazil, which has successfully established a physical science nuclear laboratory and a radio-biology centre; Venezuela, with a medico-biological centre from which much may be expected; and Mexico, where nuclear science courses are to be provided by the University of Mexico. The report discusses two alternatives for the establishment of training centres: 'specialized centres' or 'integrated centres' and concludes that the integrated centre is the preferable one however specialized centres stand a much higher chance of being staffed successfully. They are inherently smaller and consequently costs for facilities and equipment are much less. In addition use might be made of existing facilities. It is stated that one of the specialized atomic energy training centres to be established might well be in the field of radio-botany. Agriculture is a major source of income throughout Latin America. There are many agricultural schools and experimental stations throughout the region and also the Inter-American Institute of Agricultural Science at Turrialba, Costa Rica. The authors of the report concluded that a training centre in radio-botany should provide vitally needed knowledge and vitally needed specialists to all the agricultural installations in Latin America. The report recommends that (1) the Agency should meet the requests of Latin American universities by, for example, supplying equipment and sending experts; (2) at least one specialized training centre should be established

  17. Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

    Science.gov (United States)

    Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

  18. A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

    Directory of Open Access Journals (Sweden)

    Sahin Erdol MD

    2016-05-01

    Full Text Available Succinyl-CoA:3-oxoacid CoA transferase (SCOT deficiency is an autosomal recessive disorder of ketone body utilization that is clinically characterized with intermittent ketoacidosis crises. We report here the second Turkish case with SCOT deficiency. She experienced 3 ketoacidotic episodes: The first ketoacidotic crisis mimicked diabetic ketoacidosis because of the associated hyperglycemia. Among patients with SCOT deficiency, the blood glucose levels at the first crises were variable, and this case had the highest ever reported blood glucose level. She is a compound heterozygote with 2 novel mutations, c.517A>G (K173E and c.1543A>G (M515V, in exons 5 and 17 of the OXCT1 gene, respectively. In patient’s fibroblasts, SCOT activity was deficient and, by immunoblot analysis, SCOT protein was much reduced. The patient attained normal development and had no permanent ketosis. The accurate diagnosis of SCOT deficiency in this case had a vital impact on the management strategy and outcome.

  19. Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse - CSNSM/Centre for nuclear and mass spectroscopy, Activity Report 2001-2002

    International Nuclear Information System (INIS)

    2003-01-01

    The Centre for nuclear and mass spectroscopy (CSNSM) is a CNRS (National Centre for Scientific Research) laboratory affiliated with Paris-Sud University. The CSNSM is involved in pluri-disciplinary activities covering various scientific domains: Nuclear Structure (SNO), Nuclear Astrophysics (AN), Solid State Astrophysics (AS), Solid State Physics (PS) and Chemical Physics of Irradiation. This document presents the activity of the Centre during the 2001-2002 years: 1 - Foreword; 2 - Research topics: Nuclear structure; EFIX: study of exotic nuclei-induced fission; Nuclear Astrophysics; Accelerator-based mass spectroscopy; Solid State Astrophysics; Physics and Chemistry of Irradiation; Solid State Physics; SEMIRAMIS (ion source and ion beam handling); Digest science; 3 - Publications; 4 - Dissertations; 5 - Seminars; 6 - Technical services: Computer Department; Electronics Group; Mechanics Department; Permanent training; Health and safety; 7 - Staff

  20. The effluent problem in a plutonium production centre; Probleme des effluents d'un centre de production de plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Galley, R; Cantel, J [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1960-07-01

    The first part of the report is devoted to generalities: the geographical situation of the Marcoule Centre, the sources of radio-active effluent, methods of treating this effluent. In the second part the authors gives a detailed description of the various installations in the Radio-active Effluent Treatment Station at the Marcoule Centre, and outline the conditions governing the rejection of treated effluent into the Rhone. A few lines are given to comparisons between the results obtained from the use of these installations up till may 1959 and the expected results published by the same authors at the Brussels Conference (1956). In conclusion the authors lay down some of the essential principles, applicable to the study of new installations. (author) [French] La premiere partie du rapport est consacree a quelques generalites: situation geographique du Centre de Marcoule, provenance des effluents radioactifs, methodes de traitement de ces effluents. Dans la seconde partie, les auteurs presentent une description detaillee des diverses installations de la Station de Traitement des Effluents radioactifs du Centre de Marcoule et precisent les conditions de rejet dans le Rhone des effluents radioactifs traites. Quelques lignes sont consacrees aux comparaisons entre les resultats de l'exploitation des installations jusqu'en mai 1959 et les previsions publiees par les memes auteurs a l'occasion de la Conference de Bruxelles (1956). En conclusion, les auteurs donnent quelques principes essentiels, applicables a l'etude de nouvelles installations. (auteur)

  1. New and innovative exhibition concepts at science centres using communication technologies

    DEFF Research Database (Denmark)

    Quistgaard, Nana; Kahr-Højland, Anne

    2010-01-01

    Will new communication technologies mean the death of science centres, as Bradburne predicted 12 years ago-or are they alive and kicking? And if science centres do survive, what role could they possibly play in today's society? What mechanisms underlie the development of science centres...... direction, e.g., regarding the emphasised importance of facilitating scientific literacy and critical reflection. We argue that new communication technologies hold potential to accommodate new trends and that science centres have shown to be enterprising in their use of such technologies, e.g., mobile...

  2. Solution Structural Studies of GTP:Adenosylcobinamide-Phosphateguanylyl Transferase (CobY from Methanocaldococcus jannaschii.

    Directory of Open Access Journals (Sweden)

    Kiran K Singarapu

    Full Text Available GTP:adenosylcobinamide-phosphate (AdoCbi-P guanylyl transferase (CobY is an enzyme that transfers the GMP moiety of GTP to AdoCbi yielding AdoCbi-GDP in the late steps of the assembly of Ado-cobamides in archaea. The failure of repeated attempts to crystallize ligand-free (apo CobY prompted us to explore its 3D structure by solution NMR spectroscopy. As reported here, the solution structure has a mixed α/β fold consisting of seven β-strands and five α-helices, which is very similar to a Rossmann fold. Titration of apo-CobY with GTP resulted in large changes in amide proton chemical shifts that indicated major structural perturbations upon complex formation. However, the CobY:GTP complex as followed by 1H-15N HSQC spectra was found to be unstable over time: GTP hydrolyzed and the protein converted slowly to a species with an NMR spectrum similar to that of apo-CobY. The variant CobYG153D, whose GTP complex was studied by X-ray crystallography, yielded NMR spectra similar to those of wild-type CobY in both its apo- state and in complex with GTP. The CobYG153D:GTP complex was also found to be unstable over time.

  3. India | Page 90 | IDRC - International Development Research Centre

    International Development Research Centre (IDRC) Digital Library (Canada)

    Une série d'exposés de politique, fondés sur des recherches effectuées par le Centre for Urban Equity de la Centre for Environmental Planning and Technology University (CEPT University), en Inde, contient des recommandations tangibles afin d'améliorer les conditions de vie de centaines de milliers de résidents ...

  4. ICT and the location of call centres: regional and local patterns

    NARCIS (Netherlands)

    Bruinsma, Frank; Rietveld, Piet; Beekman, Michiel

    2004-01-01

    One of the sectors that gained most of the boost in ICT developments is the call centres sector. The focus in this paper is on spatial diffusion patterns of call centres in the Netherlands. The number of call centres has increased rapidly in the last decade and it seems that impacts of call

  5. International Centre for Theoretical Physics, Trieste Scientific activities in 1991

    International Nuclear Information System (INIS)

    1992-11-01

    The document contains three parts. Part 1 is a general review of the scientific activities of the Centre in 1991, including a statistical digest. Part II presents the scientific programme of the Centre in the following fields: Fundamental Physics, Condensed Matter Physics, Mathematics, Physics and Energy, Physics and Environment, Applied Physics, Adriatico Research Conferences, as well as other aspects of the Centre activities in 1991. Part III lists the publications issued in 1991. Tabs

  6. International Centre for Theoretical Physics, Trieste. Scientific activities in 1990

    International Nuclear Information System (INIS)

    1991-09-01

    The document contains three parts: Part I is a general review of the scientific activities of the Centre in 1990, including a statistical digest. Part II describes the scientific programme of the Centre in the following fields: Fundamental physics, condensed nuclear physics, mathematics, physics and energy, physics and environment, physics of the living state, applied physics Adriatico research conferences and other aspects of the Centre activities. Part III lists the publications issued in 1990

  7. Corneal aldehyde dehydrogenase and glutathione S-transferase activity after excimer laser keratectomy in guinea pigs.

    Science.gov (United States)

    Bilgihan, K; Bilgihan, A; Hasanreisoğlu, B; Turkozkan, N

    1998-03-01

    The free radical balance of the eye may be changed by excimer laser keratectomy. Previous studies have demonstrated that excimer laser keratectomy increases the corneal temperature, decreases the superoxide dismutase activity of the aqueous, and induces lipid peroxidation in the superficial corneal stroma. Aldehyde dehydrogenase (ALDH) and glutathione S-transferase (GST) are known to play an important role in corneal metabolism, particularly in detoxification of aldehydes, which are generated from free radical reactions. In three groups of guinea pigs mechanical corneal de-epithelialisation was performed in group I, superficial corneal photoablation in group II, and deep corneal photoablation in group III, and the corneal ALDH and GST activities measured after 48 hours. The mean ALDH and GST activities of group I and II showed no differences compared with the controls (p > 0.05). The corneal ALDH activities were found to be significantly decreased (p < 0.05) and GST activities increased (p < 0.05) in group III. These results suggest that excimer laser treatment of high myopia may change the ALDH and GST activities, metabolism, and free radical balance of the cornea.

  8. Importance of patient centred care for various patient groups.

    NARCIS (Netherlands)

    Rademakers, J.J.D.J.M.; Delnoij, D.M.J.; Boer, D. de

    2010-01-01

    Background: Though patient centred care is a somewhat ‘fuzzy’ concept, in general it is considered as something to strive for. However, preliminary evidence suggests that the importance of elements of patient-centred care (PCC), such as communication, information and shared decision making, may vary

  9. Mathematics in Student-­Centred Inquiry Learning: Student Engagement

    Science.gov (United States)

    Calder, Nigel

    2013-01-01

    This paper examines how mathematical understandings might be facilitated through student-centred inquiry. Data is drawn from a research project on student-centred inquiry learning that situated mathematics within authentic problem-solving contexts and involved students in a collaboratively constructed curriculum. A contemporary interpretive frame…

  10. Budapest Training Technology Centre.

    Science.gov (United States)

    Budapest Training Technology Centre (Hungary).

    The Budapest Training Technology Centre (BTTC) grew out of a 1990 agreement calling for Great Britain to help Hungary develop and implement open and flexible training methods and technology-based training to support the labor force development and vocational training needs resulting from Hungary's transition to a market economy. The BTTC would be…

  11. Description of the Nuclear Training Centre

    International Nuclear Information System (INIS)

    Wagadarikar, V.K.

    1974-01-01

    The Department of Atomic Energy, Government of India has developed an on-going programme for constructing and operating heavy water moderated, natural uranium fuelled power stations of the CANDU-type. With the view to train personnel required for operation and maintenance of these stations, a Nuclear Training Centre has been set up at the site of the Rajasthan Atomic Power Station. A description of the nuclear training centre with its facilities is given. The training programme for engineers, operators, mechanical, electrical and control maintainers etc. is given in detail, along with the actual syllabi for respective courses. Examples of the typical field check list are provided. (K.B.)

  12. Byurakan Astrophysical Observatory as Cultural Centre

    Science.gov (United States)

    Mickaelian, A. M.; Farmanyan, S. V.

    2017-07-01

    NAS RA V. Ambartsumian Byurakan Astrophysical Observatory is presented as a cultural centre for Armenia and the Armenian nation in general. Besides being scientific and educational centre, the Observatory is famous for its unique architectural ensemble, rich botanical garden and world of birds, as well as it is one of the most frequently visited sightseeing of Armenia. In recent years, the Observatory has also taken the initiative of the coordination of the Cultural Astronomy in Armenia and in this field, unites the astronomers, historians, archaeologists, ethnographers, culturologists, literary critics, linguists, art historians and other experts. Keywords: Byurakan Astrophysical Observatory, architecture, botanic garden, tourism, Cultural Astronomy.

  13. Novel derivatives of aclacinomycin A block cancer cell migration through inhibition of farnesyl transferase.

    Science.gov (United States)

    Magi, Shigeyuki; Shitara, Tetsuo; Takemoto, Yasushi; Sawada, Masato; Kitagawa, Mitsuhiro; Tashiro, Etsu; Takahashi, Yoshikazu; Imoto, Masaya

    2013-03-01

    In the course of screening for an inhibitor of farnesyl transferase (FTase), we identified two compounds, N-benzyl-aclacinomycin A (ACM) and N-allyl-ACM, which are new derivatives of ACM. N-benzyl-ACM and N-allyl-ACM inhibited FTase activity with IC50 values of 0.86 and 2.93 μM, respectively. Not only ACM but also C-10 epimers of each ACM derivative failed to inhibit FTase. The inhibition of FTase by N-benzyl-ACM and N-allyl-ACM seems to be specific, because these two compounds did not inhibit geranylgeranyltransferase or geranylgeranyl pyrophosphate (GGPP) synthase up to 100 μM. In cultured A431 cells, N-benzyl-ACM and N-allyl-ACM also blocked both the membrane localization of H-Ras and activation of the H-Ras-dependent PI3K/Akt pathway. In addition, they inhibited epidermal growth factor (EGF)-induced migration of A431 cells. Thus, N-benzyl-ACM and N-allyl-ACM inhibited EGF-induced migration of A431 cells by inhibiting the farnesylation of H-Ras and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.

  14. Discharged of the nuclear wastes by health service centres

    International Nuclear Information System (INIS)

    Mazur, G.; Jednorog, S.

    1993-01-01

    In this paper Polish national regulation in radiation protection on nuclear medical domain was discussed. The method of utilized nuclear wastes in medical and science centres was deliberate. From many years activity of wastes from Nuclear Medicine Department of Central Clinical Hospital Armed Forces Medical Academy and Radiation Protection Department of Armed Forces Institute of Hygiene and Epidemiology was measured. In debate centres radiation monitoring was performed. In this purpose the beta global activity and gamma spectrometry measurement of discharged wastes occurred. From last year in discussed centres wastes activity do not increased permissible levels. (author). 3 refs, 5 tabs

  15. Effluent treatment plant and decontamination centre, Trombay

    International Nuclear Information System (INIS)

    Kaushik, C.P.; Agarwal, K.

    2017-01-01

    The Bhabha Atomic Research Centre, Trombay, has a number of plants and laboratories, which generate Radioactive Liquid Waste and Protective Wears. Two facilities have been established in late 1960s to cater to this requirement. The Centre, on the average generates about 50,000 m"3 of active liquid effluents of varying specific activities. The Effluent Treatment Plant was setup to receive and process radioactive liquids generated by various facilities of BARC in Trombay. It also serves a single-point discharge facility to enable monitoring of radioactive effluents discharged from the Trombay site. About 120-150 Te of protective wears and inactive apparel are generated annually from various radioactive facilities and laboratories of BARC. In addition, contaminated fuel assembly components are generated by DHRUVA and formerly by CIRUS. These components require decontamination before its recycle to the fuel assembly process. The Decontamination Centre, setup in late 1960s, is mandated to carry out the above mentioned decontamination activities

  16. Medical applications in a nuclear research centre

    International Nuclear Information System (INIS)

    Vanhavere, F.; Eggermont, G.

    2001-01-01

    In these days of public aversion to nuclear power, it can be important to point at the medical applications of ionising radiation. Not only the general public, but also the authorities and research centres have to be aware of these medical applications, which are not without risk for public health. Now that funding for nuclear research is declining, an opening to the medical world can give new opportunities to a nuclear research centre. A lot of research could be done where the tools developed for the nuclear power world are very useful. Even new applications for the research reactors like BNCT (boron neutron capture therapy) can be envisaged for the near future. In this contribution an overview will be given of the different techniques used in the medical world with ionising radiation. The specific example of the Belgian Nuclear Research Centre will be given where the mission statement was changed to include a certain number of medical research topics. (authors)

  17. A day in the CERN Control Centre

    CERN Multimedia

    Rosaria Marraffino

    2015-01-01

    The CERN Control Centre (CCC) is the nerve centre of the CERN beam systems. From this room, the experts prepare, monitor, adjust, and control the particle beams that circulate throughout the accelerator complex while ensuring that the services and the technical infrastructure work flawlessly. Buttons, screens, telephones, lights (but no sound): in the CCC, everything is ready to make it possible for the LHC to reach the unprecedented energies expected at Run 2.   Seen from above, the CERN Control Centre resembles the shape of a quadrupole magnet. The consoles are distributed in four circles, called “islands”, dedicated to the LHC, the SPS, the PS Complex and the Technical Infrastructure (TI) respectively. Spread between TI and LHC are the Cryogenics consoles. Being in the same room allows the 24h-manned islands to be constantly in touch with one another, thus ensuring the best performance of the machines. At the LHC island, operators are currently busy training the magnet...

  18. Menadione stress in Saccharomyces cerevisiae strains deficient in the glutathione transferases.

    Science.gov (United States)

    Castro, F A V; Herdeiro, R S; Panek, A D; Eleutherio, E C A; Pereira, M D

    2007-02-01

    Using S. cerevisiae as a eukaryotic cell model we have analyzed the involvement of both glutathione transferase isoforms, Gtt1 and Gtt2, in constitutive resistance and adaptive response to menadione, a quinone which can exert its toxicity as redox cycling and/or electrophiles. The detoxification properties, of these enzymes, have also been analyzed by the appearance of S-conjugates in the media. Direct exposure to menadione (20 mM/60 min) showed to be lethal for cells deficient on both Gtt1 and Gtt2 isoforms. However, after pre-treatment with a low menadione concentration, cells deficient in Gtt2 displayed reduced ability to acquire tolerance when compared with the control and the Gtt1 deficient strains. Analyzing the toxic effects of menadione we observed that the gtt2 mutant showed no reduction in lipid peroxidation levels. Moreover, measuring the levels of intracellular oxidation during menadione stress we have shown that the increase of this oxidative stress parameter was due to the capacity menadione possesses in generating reactive oxygen species (ROS) and that both GSH and Gtt2 isoform were required to enhance ROS production. Furthermore, the efflux of the menadione-GSH conjugate, which is related with detoxification of xenobiotic pathways, was not detected in the gtt2 mutant. Taken together, these results suggest that acquisition of tolerance against stress generated by menadione and the process of detoxification through S-conjugates are dependent upon Gtt2 activity. This assessment was corroborated by the increase of GTT2 expression, and not of GTT1, after menadione treatment.

  19. Cultural Centre, Destination Cultural Offer and Visitor Satisfaction

    Directory of Open Access Journals (Sweden)

    Benxiang Zeng

    2017-10-01

    Full Text Available This paper aims to establish the link between tourists’ perceptions on cultural offers and their overall satisfaction, and explore the implication of this link for sustainable tourist destination management. Assessing online customers’ reviews, this study identifies a positive correlation between visitors’ perspectives and experiences at the on-site cultural centre and visitors’ destination satisfaction. It suggests that the on-site cultural centre plays a critical role in building up visitors’ perception on cultural attributes of the destination, and its impact on visitor satisfaction is a double-edged sword. Visitors’ positive perspectives on the cultural centre enhance visitors’ experiences and contribute to their destination satisfaction; however, not only does a negative perspective on their cultural and spiritual experience compromise visitors’ satisfaction, but also subsequent negative online reviews damage the destination image and discourage visitor return/visit. The findings help destination management organisations to better understand visitors’ preference for cultural centres and therefore to improve visitors’ cultural experience. This paper appeals for further study of on-site cultural centres’ role in forming destination cultural attributes, and of social media’s potential in enriching cultural experience.

  20. English language writing centres in Japanese universities: What do students really need?

    Directory of Open Access Journals (Sweden)

    Jim McKinley

    2010-06-01

    Full Text Available The installation of English language writing centres in Japanese universities is a relatively recent event—the first ones established with funding from the Ministry of Education in 2004. Because of the EFL writing context, setting up a writing centre requires consideration of students’ needs and cultural expectations of writing and writing centres. In general, writing centres that have been established in Japanese universities follow a structure similar to those in the US. This raises the question as to whether or not this is appropriate for the particular needs of EFL students and the obstacles they face. For this study, in order to explore students’ attitudes toward writing centres and the role they play in writing education, interview data was collected from students of English composition in two different departments at a university in Japan well known for its English language education: the English department, which does not have a writing centre, and the liberal arts department, which has one of the first writing centres established in Japan.

  1. Cost-effectiveness of planned birth in a birth centre compared with alternative planned places of birth: Results of the Dutch Birth Centre study

    NARCIS (Netherlands)

    M.F. Hitzert (Marit); M.A.A. Hermus (Marieke A.A.); Boesveld, I.I.C. (Inge I.C.); A. Franx (Arie); K.M. van der Pal-De Bruin (Karin); E.A.P. Steegers (Eric); Van Den Akker-Van Marle, E.M.E. (Eiske M.E.)

    2017-01-01

    textabstractObjectives To estimate the cost-effectiveness of a planned birth in a birth centre compared with alternative planned places of birth for low-risk women. In addition, a distinction has been made between different types of locations and integration profiles of birth centres. Design

  2. Soft X-ray excited colour-centre luminescence and XANES studies of calcium oxide

    International Nuclear Information System (INIS)

    Ko, J.Y.P.; Heigl, F.; Yiu, Y.M.; Zhou, X.-T.; Regier, T.; Blyth, R.I.R.; Sham, T.-K.

    2007-01-01

    In this study, we show that colour centres can be produced by irradiating calcium oxide with soft X-rays from a synchrotron radiation source. Using the X-ray excited optical Iuminescence (XEOL) technique, two colour centres, F-centre, and F + -centre can be identified. These colour centres emit photons at characteristic wavelengths. In addition, by performing time-resolved XEOL (TRXEOL), we are able to reveal timing and decay characteristics of the colour centres. We also present X-ray absorption near-edge structure (XANES) spectra collected across oxygen K-edge, calcium L 3,2 -edge, and calcium K-edge. Experimental results are compared with density functional theory (DFT) calculations. (author)

  3. The programme benefits of improving project team communication through a contact centre

    Directory of Open Access Journals (Sweden)

    Bond-Barnard, T. J.

    2013-08-01

    Full Text Available A South African national programme to repair government infrastructure uses a contact centre (or call centre to facilitate and manage communication. An important question is: How does the contact centre benefit the programme and its projects? This study discusses the findings of a survey that quantified the benefits of the programme when the communication between team members in the programme was improved by using a contact centre. The results show that, by using a contact centre to improve the communication between project team members, their perception of communication effectiveness, quality of project deliverables, service delivery, and customer satisfaction of the programme dramatically increases.

  4. Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse - CSNSM/Centre for nuclear and mass spectroscopy, Activity Report 2002-2004

    International Nuclear Information System (INIS)

    2005-01-01

    The Centre for nuclear and mass spectroscopy (CSNSM) is a CNRS (National Centre for Scientific Research) laboratory affiliated with Paris-Sud University. The CSNSM is involved in pluri-disciplinary activities covering various scientific domains: Nuclear Structure (SNO), Nuclear Astrophysics (AN), Solid State Astrophysics (AS), Solid State Physics (PS) and Chemical Physics of Irradiation. This document presents the activity of the Centre during the 2002-2004 years: 1 - Foreword; 2 - Nuclear structure; 3 - EFIX: study of exotic nuclei-induced fission; 4 - Nuclear Astrophysics; 5 - Atomic mass; 6 - Solid state astrophysics; 7 - Accelerator-based mass spectroscopy; 8 - Solid State Physics; 9 - Physics and Chemistry of Irradiation; 10 - Activities of general interest; 11 - SEMIRAMIS (ion source and ion beam handling); 12 - Computer Department; 13 - Electronics Group; 14 - Mechanics Department; 15 - Health and safety; 16 - Permanent training; 17 - Seminars; 18 - PhDs; 19 - Staff

  5. Coordonnateur du bureau d'assistance | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Résumé des fonctions. En tant que membre de l'équipe du Bureau d'assistance au sein de la Section du service à la clientèle (SSC), le coordonnateur du Bureau d'assistance offre au personnel du Centre et aux autres utilisateurs reconnus des installations TI du Centre un soutien de première ligne en matière d'utilisation ...

  6. Human glutathione transferases catalyzing the bioactivation of anticancer thiopurine prodrugs.

    Science.gov (United States)

    Eklund, Birgitta I; Gunnarsdottir, Sjofn; Elfarra, Adnan A; Mannervik, Bengt

    2007-06-01

    cis-6-(2-Acetylvinylthio)purine (cAVTP) and trans-6-(2-acetylvinylthio)guanine (tAVTG) are thiopurine prodrugs provisionally inactivated by an alpha,beta-unsaturated substituent on the sulfur of the parental thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). The active thiopurines are liberated intracellularly by glutathione (GSH) in reactions catalyzed by glutathione transferases (GSTs) (EC 2.5.1.18). Catalytic activities of 13 human GSTs representing seven distinct classes of soluble GSTs have been determined. The bioactivation of cAVTP and tAVTG occurs via a transient addition of GSH to the activated double bond of the S-substituent of the prodrug, followed by elimination of the thiopurine. The first of these consecutive reactions is rate-limiting for thiopurine release, but GST-activation of this first addition is shifting the rate limitation to the subsequent elimination. Highly active GSTs reveal the transient intermediate, which is detectable by UV spectroscopy and HPLC analysis. LC/MS analysis of the reaction products demonstrates that the primary GSH conjugate, 4-glutathionylbuten-2-one, can react with a second GSH molecule to form the 4-(bis-glutathionyl)butan-2-one. GST M1-1 and GST A4-4 were the most efficient enzymes with tAVTG, and GST M1-1 and GST M2-2 had highest activity with cAVTP. The highly efficient GST M1-1 is polymorphic and is absent in approximately half of the human population. GST P1-1, which is overexpressed in many cancer cells, had no detectable activity with cAVTP and only minor activity with tAVTG. Other GST-activated prodrugs have targeted GST P1-1-expressing cancer cells. Tumors expressing high levels of GST M1-1 or GST A4-4 can be predicted to be particularly vulnerable to chemotherapy with cAVTP or tAVTG.

  7. The DEMETER Science Mission Centre

    Czech Academy of Sciences Publication Activity Database

    Lagoutte, D.; Brochot, J.; Y.; de Carvalho, D.; Elie, F.; Harivelo, F.; Hobara, Y.; Madrias, L.; Parrot, M.; Pincon, J. L.; Berthelier, J. J.; Peschard, D.; Seran, E.; Gangloff, M.; Sauvaud, J. A.; Lebreton, J. P.; Štverák, Štěpán; Trávníček, Pavel M.; Grygorczuk, J.; Slominski, J.; Wronowski, R.; Barbier, S.; Bernard, P.; Gaboriaud, A.; Wallut, J. M.

    2006-01-01

    Roč. 54, č. 5 (2006), s. 428-440 ISSN 0032-0633 Institutional research plan: CEZ:AV0Z30420517 Keywords : Mission Centre * Data processing Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 1.509, year: 2006

  8. Thermoluminiscence and thermal annealing of F centres in KCL gamma irradiated

    International Nuclear Information System (INIS)

    Ausin Alonso, Vicente.

    1976-01-01

    The thermoluminiscence spectrum and phosphorescence decays of Harshaw KCl samples gamma irradiated at room temperature have been studied up to 400 0 C. For the six peaks found, the order of recombination kinetics, the pre-exponential factor and the activation energy have been obtained. It has been observed that the area under the thermoluminiscence curve is always proportional to the F centre concentration in the sample before heating. It was also found that there is an annealing step of F centres corresponding to each thermoluminiscence peak, when the temperature of the sample is raised at a constant rate. It is concluded that the F centres play the role of recombination centres in the annealing process, the interstitials being the mobile entities moving towards there combination centre. At some stage in the process light is emitted. (author)

  9. Experience building and operating the CMS Tier-1 computing centres

    Science.gov (United States)

    Albert, M.; Bakken, J.; Bonacorsi, D.; Brew, C.; Charlot, C.; Huang, Chih-Hao; Colling, D.; Dumitrescu, C.; Fagan, D.; Fassi, F.; Fisk, I.; Flix, J.; Giacchetti, L.; Gomez-Ceballos, G.; Gowdy, S.; Grandi, C.; Gutsche, O.; Hahn, K.; Holzman, B.; Jackson, J.; Kreuzer, P.; Kuo, C. M.; Mason, D.; Pukhaeva, N.; Qin, G.; Quast, G.; Rossman, P.; Sartirana, A.; Scheurer, A.; Schott, G.; Shih, J.; Tader, P.; Thompson, R.; Tiradani, A.; Trunov, A.

    2010-04-01

    The CMS Collaboration relies on 7 globally distributed Tier-1 computing centres located at large universities and national laboratories for a second custodial copy of the CMS RAW data and primary copy of the simulated data, data serving capacity to Tier-2 centres for analysis, and the bulk of the reprocessing and event selection capacity in the experiment. The Tier-1 sites have a challenging role in CMS because they are expected to ingest and archive data from both CERN and regional Tier-2 centres, while they export data to a global mesh of Tier-2s at rates comparable to the raw export data rate from CERN. The combined capacity of the Tier-1 centres is more than twice the resources located at CERN and efficiently utilizing this large distributed resources represents a challenge. In this article we will discuss the experience building, operating, and utilizing the CMS Tier-1 computing centres. We will summarize the facility challenges at the Tier-1s including the stable operations of CMS services, the ability to scale to large numbers of processing requests and large volumes of data, and the ability to provide custodial storage and high performance data serving. We will also present the operations experience utilizing the distributed Tier-1 centres from a distance: transferring data, submitting data serving requests, and submitting batch processing requests.

  10. Experience building and operating the CMS Tier-1 computing centres

    International Nuclear Information System (INIS)

    Albert, M; Bakken, J; Huang, Chih-Hao; Dumitrescu, C; Fagan, D; Fisk, I; Giacchetti, L; Gutsche, O; Holzman, B; Bonacorsi, D; Grandi, C; Brew, C; Jackson, J; Charlot, C; Colling, D; Fassi, F; Flix, J; Gomez-Ceballos, G; Hahn, K; Gowdy, S

    2010-01-01

    The CMS Collaboration relies on 7 globally distributed Tier-1 computing centres located at large universities and national laboratories for a second custodial copy of the CMS RAW data and primary copy of the simulated data, data serving capacity to Tier-2 centres for analysis, and the bulk of the reprocessing and event selection capacity in the experiment. The Tier-1 sites have a challenging role in CMS because they are expected to ingest and archive data from both CERN and regional Tier-2 centres, while they export data to a global mesh of Tier-2s at rates comparable to the raw export data rate from CERN. The combined capacity of the Tier-1 centres is more than twice the resources located at CERN and efficiently utilizing this large distributed resources represents a challenge. In this article we will discuss the experience building, operating, and utilizing the CMS Tier-1 computing centres. We will summarize the facility challenges at the Tier-1s including the stable operations of CMS services, the ability to scale to large numbers of processing requests and large volumes of data, and the ability to provide custodial storage and high performance data serving. We will also present the operations experience utilizing the distributed Tier-1 centres from a distance: transferring data, submitting data serving requests, and submitting batch processing requests.

  11. Directeur, administration des subventions (h/f) | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Diriger l'élaboration de politiques régissant l'administration de projets du Centre ... Tenir à jour un aperçu stratégique des activités de projet du Centre afin d'en .... Gérer le recrutement du personnel de l'administration des subventions dans ...

  12. Role of Stakeholders at Cape Coast PPAG Youth Centre ...

    African Journals Online (AJOL)

    The study investigated whether the activities or the roles performed by the various stakeholders at the Cape Coast Planned Parenthood Association of Ghana (PPAG) youth centre impacted positively on the youth behaviour and performance at the centre. The sample comprised 22 teachers, 50 parents and 3 social welfare ...

  13. Centres and limit cycles for an extended Kukles system

    Directory of Open Access Journals (Sweden)

    Jane M. Pearson

    2007-09-01

    Full Text Available We present conditions for the origin to be a centre for a class of cubic systems. Some of the centre conditions are determined by finding complicated invariant functions. We also investigate the coexistence of fine foci and the simultaneous bifurcation of limit cycles from them.

  14. A woman-centred childbirth model | Maputle | Health SA Gesondheid

    African Journals Online (AJOL)

    A model for woman-centred childbirth was developed through four phases in accordance with the objectives of the study, namely, a description of mothers' experiences of childbirth and that of attending midwives of managing mothers during childbirth concept analysis of woman-centred care, model development, and an ...

  15. Cost-effectiveness of planned birth in a birth centre compared with alternative planned places of birth: results of the Dutch Birth Centre study

    NARCIS (Netherlands)

    Hitzert, M.; Hermus, M.M.; Boesveld, I.I.; Franx, A.; Pal-de Bruin, K.K. van der; Steegers, E.E.; Akker-van Marle, E.M. van den

    2017-01-01

    Objectives To estimate the cost-effectiveness of a planned birth in a birth centre compared with alternative planned places of birth for low-risk women. In addition, a distinction has been made between different types of locations and integration profiles of birth centres. Design Economic evaluation

  16. Cost-effectiveness of planned birth in a birth centre compared with alternative planned places of birth : Results of the Dutch Birth Centre study

    NARCIS (Netherlands)

    Hitzert, Marit F.; Hermus, Marieke A. A.; Boesveld, Inge I.C.; Franx, Arie; van der Pal-de Bruin, Karin M.; Steegers, Eric A. P.; Van Den Akker-Van Marle, Eiske M.E.

    2017-01-01

    Objectives To estimate the cost-effectiveness of a planned birth in a birth centre compared with alternative planned places of birth for low-risk women. In addition, a distinction has been made between different types of locations and integration profiles of birth centres. Design Economic evaluation

  17. Developing and testing the patient-centred innovation questionnaire for hospital nurses.

    Science.gov (United States)

    Huang, Ching-Yuan; Weng, Rhay-Hung; Wu, Tsung-Chin; Lin, Tzu-En; Hsu, Ching-Tai; Hung, Chiu-Hsia; Tsai, Yu-Chen

    2018-03-01

    Develop the patient-centred innovation questionnaire for hospital nurses and establish its validity and reliability. Patient-centred care has been adopted by health care managers in their efforts to improve health care quality. It is regarded as a core concept for developing innovation. A cross-sectional study was employed to collect data from hospital nurses in Taiwan. This study was divided into two stages: pilot study and main study. In the main study, 596 valid responses were collected. This study adopted reliability analysis, exploratory factor analysis, confirmatory factor analysis and selected nurse innovation scale as a criterion to test criterion-related validity. Five-dimension patient-centred innovation questionnaire was proposed: access and practicability, co-ordination and communication, sharing power and responsibility, care continuity, family and person focus. Each dimension demonstrated a reliability of 0.89-0.98. All dimensions had acceptable convergent and discriminate validity. The patient-centred innovation questionnaire and nurse innovation scale exhibited a significantly positive correlation. Patient-centred innovation questionnaire not only had a good theoretical basis but also had sufficient reliability and construct validity, and criterion-related validity. Patient-centred innovation questionnaire could give a measure for evaluating the implementation of patient-centred care and could be used as a management tool during the process of nurse innovation. © 2017 John Wiley & Sons Ltd.

  18. CENTRE OF THE MAIN INTERESTS

    Directory of Open Access Journals (Sweden)

    DIANA DELEANU

    2013-05-01

    Full Text Available The centre of the main interests of the debtor is a legal tool meant to settle conflicts that can arise between jurisdictions in cross-border insolvencies, based on the principles of mutual recognition and co-operation.

  19. The Australian Centre for Minesite Rehabilitation Research

    International Nuclear Information System (INIS)

    Bell, L.C.

    1994-01-01

    The Australian Centre for Minesite Rehabilitation Research (ACMRR) is a joint venture between the Australian mining industry through the Australian Mineral Industries Research Association Ltd. (AMIRA) and three of the organizations working most actively in this area in Australia: CSIRO Minesite Rehabilitation Research Program; University of Queensland Centre for Mined Land Rehabilitation; and Curtin University Mulga Research Centre. The ACMRR was established in July 1993 to provide a national framework to conduct Strategic Research into minesite rehabilitation. It is an industry led and funded initiative. The Goals of the Centre include: to conduct strategic research into minesite rehabilitation to provide sustainable environmental solutions which are acceptable to industry, government and the community; to be recognized as a center of excellence undertaking commissioned research on minesite rehabilitation in an independent and thorough manner; to provide scientific and technological foundations to facilitate industry and government in setting acceptable standards; to act as networking and communications focus; and to enhance education and training in minesite rehabilitation. Strategic Research Programs in: Water Systems--downstream surface and groundwater quality; Land--the long-term behavior and stability of constructed landforms; Ecosystems--the long-term sustainability of constructed landforms; Waste--the long-term treatment and disposal of waste products; will allow the ACMRR to achieve these goals through specific research projects in these areas, developed with industry sponsors. This paper will discuss their progress to date, research projects underway, and plans for the future

  20. The experience of work in a call centre environment

    Directory of Open Access Journals (Sweden)

    Sanet Hauptfleisch

    2006-10-01

    Full Text Available This qualitative research study explored the work experience in a call centre environment in an information technology call centre based in South Africa, which service foreign customers exclusively. Three data collection methods were used, namely narratives, in-depth interviews with call centre consultants, and observation. Following a grounded theory approach, four themes were elicited, namely the perceptions of team members, uncertainty created by a constantly changing environment, perceived distances due to management practices, and depersonalisation experienced while actually dealing with customers. In addition to this, the reported impact of these themes on work performance was explored and compared to existing research.