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Sample records for biphenyl dioxygenase genes

  1. NUCLEOTIDE SEQUENCING AND TRANSCRIPTIONAL MAPPING OF THE GENES ENCODING BIPHENYL DIOXYGENASE, A MULTICOM- PONENT POLYCHLORINATED-BIPHENYL-DEGRADING ENZYME IN PSEUDOMONAS STRAIN LB400

    Science.gov (United States)

    The DNA region encoding biphenyl dioxygenase, the first enzyme in the biphenyl-polychlorinated biphenyl degradation pathway of Pseudomonas species strain LB400, was sequenced. Six open reading frames were identified, four of which are homologous to the components of toluene dioxy...

  2. Metabolism of chlorobiphenyls by a variant biphenyl dioxygenase exhibiting enhanced activity toward dibenzofuran

    International Nuclear Information System (INIS)

    Viger, Jean-François; Mohammadi, Mahmood; Barriault, Diane; Sylvestre, Michel

    2012-01-01

    Highlights: ► Burkholderia xenovorans LB400 biphenyl dioxygenase (BphAE LB400 ) metabolizes PCBs. ► Asn338Gln/Leu409Phe double mutation speeds up electron transfer of enzyme reaction. ► We tested how the mutations affect the PCB-degrading abilities of BphAE LB400 variants. ► The same mutations also broaden the PCB substrate range of BphAE LB400 variants. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE LB400 ) catalyzes the dihydroxylation of biphenyl and of several polychlorinated biphenyls (PCBs) but it poorly oxidizes dibenzofuran. In this work we showed that BphAE RR41 , a variant which was previously found to metabolize dibenzofuran more efficiently than its parent BphAE LB400 , metabolized a broader range of PCBs than BphAE LB400 . Hence, BphAE RR41 was able to metabolize 2,6,2′,6′-, 3,4,3′,5′- and 2,4,3′,4′-tetrachlorobiphenyl that BphAE LB400 is unable to metabolize. BphAE RR41 was obtained by changing Thr335Phe336Asn338Ile341Leu409 of BphAE LB400 to Ala335Met336Gln338Val341Phe409. Site-directed mutagenesis was used to create combinations of each substitution, in order to assess their individual contributions. Data show that the same Asn338Glu/Leu409Phe substitution that enhanced the ability to metabolize dibenzofuran resulted in a broadening of the PCB substrates range of the enzyme. The role of these substitutions on regiospecificities toward selected PCBs is also discussed.

  3. Metabolism of chlorobiphenyls by a variant biphenyl dioxygenase exhibiting enhanced activity toward dibenzofuran

    Energy Technology Data Exchange (ETDEWEB)

    Viger, Jean-Francois; Mohammadi, Mahmood; Barriault, Diane [Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Quebec, Canada H4K 1C2 (Canada); Sylvestre, Michel, E-mail: Michel.Sylvestre@iaf.inrs.ca [Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Quebec, Canada H4K 1C2 (Canada)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Burkholderia xenovorans LB400 biphenyl dioxygenase (BphAE{sub LB400}) metabolizes PCBs. Black-Right-Pointing-Pointer Asn338Gln/Leu409Phe double mutation speeds up electron transfer of enzyme reaction. Black-Right-Pointing-Pointer We tested how the mutations affect the PCB-degrading abilities of BphAE{sub LB400} variants. Black-Right-Pointing-Pointer The same mutations also broaden the PCB substrate range of BphAE{sub LB400} variants. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE{sub LB400}) catalyzes the dihydroxylation of biphenyl and of several polychlorinated biphenyls (PCBs) but it poorly oxidizes dibenzofuran. In this work we showed that BphAE{sub RR41}, a variant which was previously found to metabolize dibenzofuran more efficiently than its parent BphAE{sub LB400}, metabolized a broader range of PCBs than BphAE{sub LB400}. Hence, BphAE{sub RR41} was able to metabolize 2,6,2 Prime ,6 Prime -, 3,4,3 Prime ,5 Prime - and 2,4,3 Prime ,4 Prime -tetrachlorobiphenyl that BphAE{sub LB400} is unable to metabolize. BphAE{sub RR41} was obtained by changing Thr335Phe336Asn338Ile341Leu409 of BphAE{sub LB400} to Ala335Met336Gln338Val341Phe409. Site-directed mutagenesis was used to create combinations of each substitution, in order to assess their individual contributions. Data show that the same Asn338Glu/Leu409Phe substitution that enhanced the ability to metabolize dibenzofuran resulted in a broadening of the PCB substrates range of the enzyme. The role of these substitutions on regiospecificities toward selected PCBs is also discussed.

  4. Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pravindra; Mohammadi, Mahmood; Dhindwal, Sonali; Pham, Thi Thanh My; Bolin, Jeffrey T.; Sylvestre, Michel (INRS); (IIT-India); (Purdue)

    2012-06-28

    The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE{sub LB400}) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAE{sub LB400} and obtained BphAE{sub RR41}. This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAE{sub LB400}. However, the regiospecificity of BphAE{sub RR41} toward these substrates differs. Dibenzofuran is metabolized principally through a lateral dioxygenation whereas 2-chlorodibenzofuran is metabolized principally through an angular dioxygenation. In order to explain this difference, we examined the crystal structures of both substrate-bound forms of BphAE{sub RR41} obtained under anaerobic conditions. This structure analysis, in combination with biochemical data for a Ser283Gly mutant provided evidences that the substrate is compelled to move after oxygen-binding in BphAE{sub RR41}:dibenzofuran. In BphAE{sub RR41}:2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAE{sub RR41}:dibenzofuran, and strong enough in the BphAE{sub RR41}:2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

  5. Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pravindra [Department of Biological Sciences and Center for Cancer Research, Purdue University, West Lafayette, IN 47907 (United States); Department of Biotechnology, Indian Institute of Technology, Roorkee 247667 (India); Mohammadi, Mahmood [Institut National de la Recherche Scientifique (INRS-Institut Armand-Frappier), Laval, QC, Canada H7V 1B7 (Canada); Dhindwal, Sonali [Department of Biotechnology, Indian Institute of Technology, Roorkee 247667 (India); Pham, Thi Thanh My [Institut National de la Recherche Scientifique (INRS-Institut Armand-Frappier), Laval, QC, Canada H7V 1B7 (Canada); Bolin, Jeffrey T. [Department of Biological Sciences and Center for Cancer Research, Purdue University, West Lafayette, IN 47907 (United States); Sylvestre, Michel, E-mail: Michel.Sylvestre@iaf.inrs.ca [Institut National de la Recherche Scientifique (INRS-Institut Armand-Frappier), Laval, QC, Canada H7V 1B7 (Canada)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Regiospecificity of BphAE{sub RR41} toward dibenzofuran and 2-chlorodibenzofuran differs. Black-Right-Pointing-Pointer We compared the structures of the substrate-bound forms of the enzyme with both substrates. Black-Right-Pointing-Pointer Dibenzofuran is compelled to move during the catalytic reaction. Black-Right-Pointing-Pointer Ser283 contact with 2-chlorodibenzofuran helps prevent substrate movement during the reaction. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE{sub LB400}) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAE{sub LB400} and obtained BphAE{sub RR41}. This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAE{sub LB400}. However, the regiospecificity of BphAE{sub RR41} toward these substrates differs. Dibenzofuran is metabolized principally through a lateral dioxygenation whereas 2-chlorodibenzofuran is metabolized principally through an angular dioxygenation. In order to explain this difference, we examined the crystal structures of both substrate-bound forms of BphAE{sub RR41} obtained under anaerobic conditions. This structure analysis, in combination with biochemical data for a Ser283Gly mutant provided evidences that the substrate is compelled to move after oxygen-binding in BphAE{sub RR41}:dibenzofuran. In BphAE{sub RR41}:2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAE{sub RR41}:dibenzofuran, and strong enough in the BphAE{sub RR41}:2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

  6. Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase

    International Nuclear Information System (INIS)

    Kumar, Pravindra; Mohammadi, Mahmood; Dhindwal, Sonali; Pham, Thi Thanh My; Bolin, Jeffrey T.; Sylvestre, Michel

    2012-01-01

    Highlights: ► Regiospecificity of BphAE RR41 toward dibenzofuran and 2-chlorodibenzofuran differs. ► We compared the structures of the substrate-bound forms of the enzyme with both substrates. ► Dibenzofuran is compelled to move during the catalytic reaction. ► Ser283 contact with 2-chlorodibenzofuran helps prevent substrate movement during the reaction. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE LB400 ) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAE LB400 and obtained BphAE RR41 . This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAE LB400 . However, the regiospecificity of BphAE RR41 toward these substrates differs. Dibenzofuran is metabolized principally through a lateral dioxygenation whereas 2-chlorodibenzofuran is metabolized principally through an angular dioxygenation. In order to explain this difference, we examined the crystal structures of both substrate-bound forms of BphAE RR41 obtained under anaerobic conditions. This structure analysis, in combination with biochemical data for a Ser283Gly mutant provided evidences that the substrate is compelled to move after oxygen-binding in BphAE RR41 :dibenzofuran. In BphAE RR41 :2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAE RR41 :dibenzofuran, and strong enough in the BphAE RR41 :2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

  7. Purification of Biotransformation Products of Cis-Isoflavan-4-ol by Biphenyl Dioxygenase of Pseudomonas pseudoalcaligenes KF707 Strain Expressed in Escherichia coli

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    Tri Ratna Sulistiyani

    2013-04-01

    Full Text Available Isoflavone has multiple beneficial effects on human health, especially through its antioxidant and anticancer activities. The biotransformation of isoflavone using byphenyl dioxygenase could be performed to extend the diversity of flavonoids and to improve their biological and physiological properties. Biotransformation of two enantiomers (3R, 4R-cis-isoflavan-4-ol and (3S, 4S-cis-isoflavan-4-ol by E. coli JM109 (pJHF108 carrying a biphenyl dioxygenase gene from P. pseudoalcaligenesKF707 produced two products, designated as CM1 andCM2. The products had a retention time of 11.9 and 14.6 min, respectively, and the same absorption peaks at 204, 220, and 275 nm. CM1 and CM2 had [M-H2O+H]+ at m/z 225. Based on the molecular mass and hydrolysis products, we proposed that epoxidation occurred on cis-isoflavan-4-ol. Chloroform extraction instead of ethyl acetate extraction was performed to improve the stability of cismetabolites, CM1 and CM2.

  8. Ability of bacterial biphenyl dioxygenases from Burkholderia sp. LB400 and Comamonas testosteroni B-356 to catalyse oxygenation of ortho-hydroxychlorobiphenyls formed from PCBs by plants

    Czech Academy of Sciences Publication Activity Database

    Francová, K.; Macková, M.; Macek, Tomáš; Sylvestre, M.

    2004-01-01

    Roč. 127, - (2004), s. 41-48 ISSN 0269-7491 R&D Projects: GA ČR GA526/01/1292 Grant - others:Natural Science and Engineering Research(CA) RGPIN39579-02; NATO Collaborative linkage(XE) SA(EST.GLC.977477)5941SA Institutional research plan: CEZ:AV0Z4055905 Keywords : PCB degradation * biphenyl dioxygenases * enzyme specificity Subject RIV: CE - Biochemistry Impact factor: 2.205, year: 2004

  9. Ability of bacterial biphenyl dioxygenases from Burkholderia sp. LB400 and Comamonas testosteroni B-356 to catalyse oxygenation of ortho-hydroxychlorobiphenyls formed from PCBs by plants

    International Nuclear Information System (INIS)

    Francova, K.; Mackova, M.; Macek, T.; Sylvestre, M.

    2004-01-01

    Bacterial dioxygenases are useful in breakdown of PCB products associated with plants. - Capacity of enzymes of the biphenyl/chlorobiphenyl pathway, especially biphenyl dioxygenase (BPDO) of two polychlorinated biphenyls (PCB) degrading bacteria, Burkholderia sp. LB400 and Comamonas testosteroni B-356, to metabolize ortho-substituted hydroxybiphenyls was tested.,These compounds found among plant products of PCB metabolism, are carrying chlorine atoms on the hydroxyl-substituted ring. The abilities of His-tagged purified LB400 and B-356 BPDOs to catalyze the oxygenation of 2-hydroxy-3-chlorobiphenyl, 2-hydroxy-5-chlorobiphenyl and 2-hydroxy-3,5-dichlorobiphenyl were compared. Both enzyme preparations catalyzed the hydroxylation of the three chloro-hydroxybiphenyls on the non-substituted ring. Neither LB400 BPDO nor B-356 BPDO oxygenated the substituted ring of the ortho-hydroxylated biphenyl. The fact that metabolites generated by both enzymes were identical for all three hydroxychlorobiphenyls tested; exclude any other mode of attack of these compounds by LB400 BPDOs than the ortho-meta oxygenation

  10. Diversity of 16S rRNA and dioxygenase genes detected in coal-tar-contaminated site undergoing active bioremediation

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, M; Khanna, S [NIIT Univ, Neemrana (India). Dept. of Biotechnology & Bioinformation

    2010-04-15

    In order to develop effective bioremediation strategies for polyaromatic hydrocarbons (PAHs) degradation, the composition and metabolic potential of microbial communities need to be better understood, especially in highly PAH contaminated sites in which little information on the cultivation-independent communities is available. Coal-tar-contaminated soil was collected, which consisted of 122-122.5 mg g{sup -1} total extractable PAH compounds. Biodegradation studies with this soil indicated the presence of microbial community that is capable of degrading the model PAH compounds viz naphthalene, phenanthrene and pyrene at 50 ppm each. PCR clone libraries were established from the DNA of the coal-tar-contaminated soil, targeting the 16S rRNA to characterize (I) the microbial communities, (ii) partial gene fragment encoding the Rieske iron sulfur center {alpha}-subunit) common to all PAH dioxygenase enzymes and (iii) {beta}-subunit of dioxygenase. Phylotypes related to Proteobacteria ({Alpha}-, {Epsilon}- and Gammaproteobacteria), Acidobacteria, Actinobacteria, Firmicutes, Gemmatimonadetes and Deinococci were detected in 16S rRNA derived clone libraries. Many of the gene fragment sequences of alpha-subunit and beta-subunit of dioxygenase obtained from the respective clone libraries fell into clades that are distinct from the reference dioxygenase gene sequences. Presence of consensus sequence of the Rieske type (2Fe2S) cluster binding site suggested that these gene fragments encode for {alpha}-subunit of dioxygenase gene. Sequencing of the cloned libraries representing {alpha}-subunit gene fragments (Rf1) and beta-subunit of dioxygenase showed the presence of hitherto unidentified dioxygenase in coal-tar-contaminated soil.

  11. Novel mutations in the homogentisate 1,2 dioxygenase gene identified in Jordanian patients with alkaptonuria.

    Science.gov (United States)

    Al-sbou, Mohammed

    2012-06-01

    This study was conducted to identify mutations in the homogentisate 1,2 dioxygenase gene (HGD) in alkaptonuria patients among Jordanian population. Blood samples were collected from four alkaptonuria patients, four carriers, and two healthy volunteers. DNA was isolated from peripheral blood. All 14 exons of the HGD gene were amplified using the polymerase chain reaction (PCR) technique. The PCR products were then purified and analyzed by sequencing. Five mutations were identified in our samples. Four of them were novel C1273A, T1046G, 551-552insG, T533G and had not been previously reported, and one mutation T847C has been described before. The types of mutations identified were two missense mutations, one splice site mutation, one frameshift mutation, and one polymorphism. We present the first molecular study of the HGD gene in Jordanian alkaptonuria patients. This study provides valuable information about the molecular basis of alkaptonuria in Jordanian population.

  12. Highly Efficient Stable Expression of Indoleamine 2,3 Dioxygenase Gene in Primary Fibroblasts

    Directory of Open Access Journals (Sweden)

    Rezakhanlou Alireza

    2010-03-01

    Full Text Available Abstract Indoleamine 2,3 dioxygenase (IDO is a potent immunomodulatory enzyme that has recently attracted significant attention for its potential application as an inducer of immunotolerance in transplantation. We have previously demonstrated that a collagen matrix populated with IDO-expressing fibroblasts can be applied successfully in suppressing islet allogeneic immune response. Meanwhile, a critical aspect of such immunological intervention relies largely on effective long-term expression of the IDO gene. Moreover, gene manipulation of primary cells is known to be challenging due to unsatisfactory expression of the exogenous gene. In this study, a lentiviral gene delivery system has been employed to transduce primary fibroblasts. We used polybrene to efficiently deliver the IDO gene into primary fibroblasts and showed a significant increase (about tenfold in the rate of gene transfection. In addition, by the use of fluorescence-activated cell sorting, a 95% pure population of IDO-expressing fibroblasts was successfully obtained. The efficiency of the IDO expression and the activity of the enzyme have been confirmed by Western blotting, fluorescence-activated cell sorting analysis, and Kynurenine assay, respectively. The findings of this study revealed simple and effective strategies through which an efficient and stable expression of IDO can be achieved for primary cells which, in turn, significantly improves its potential as a tool for achieving immunotolerance in different types of transplantation.

  13. Diversity and distribution of catechol 2, 3-dioxygenase genes in surface sediments of the Bohai Sea.

    Science.gov (United States)

    He, Peiqing; Li, Li; Liu, Jihua; Bai, Yazhi; Fang, Xisheng

    2016-05-01

    Catechol 2, 3-dioxygenase (C23O) is the key enzyme for aerobic aromatic degradation. Based on clone libraries and quantitative real-time polymerase chain reaction, we characterized diversity and distribution patterns of C23O genes in surface sediments of the Bohai Sea. The results showed that sediments of the Bohai Sea were dominated by genes related to C23O subfamily I.2.A. The samples from wastewater discharge area (DG) and aquaculture farm (KL) showed distinct composition of C23O genes when compared to the samples from Bohai Bay (BH), and total organic carbon was a crucial determinant accounted for the composition variation. C6BH12-38 and C2BH2-35 displayed the highest gene copies and highest ratios to the 16S rRNA genes in KL, and they might prefer biologically labile aromatic hydrocarbons via aquaculture inputs. Meanwhile, C7BH3-48 showed the highest gene copies and highest ratios to the 16S rRNA genes in DG, and this could be selective effect of organic loadings from wastewater discharge. An evident increase in C6BH12-38 and C7BH3-48 gene copies and reduction in diversity of C23O genes in DG and KL indicated composition perturbations of C23O genes and potential loss in functional redundancy. We suggest that ecological habitat and trophic specificity could shape the distribution of C23O genes in the Bohai Sea sediments. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Expression Profile of Carotenoid Cleavage Dioxygenase Genes in Summer Squash (Cucurbita pepo L.).

    Science.gov (United States)

    González-Verdejo, Clara I; Obrero, Ángeles; Román, Belén; Gómez, Pedro

    2015-06-01

    Carotenoids are important dietary components that can be found in vegetable crops. The accumulation of these compounds in fruit and vegetables is altered by the activity of carotenoid cleavage dioxygenases (CCDs) enzymes that produce their degradation. The aim of this work was to study the possible implication of CCD genes in preventing carotenoid storage in the horticultural crop summer squash (Cucurbita pepo L.). The relationship between the presence of these compounds and gene expression for CCDs was studied in three varieties showing different peel and flesh colour. Expression analysis for the CCD genes CpNCED1, CpNCED2, CpNCED3, CpNCED9, CpCCD1, CpCCD4a, CpCCD4b and CpCCD8 was carried out on different organs and at several fruit developmental stages. The results showed that the CpCCD4a and CpCCD4b genes were highly expressed in the variety with lowest carotenoid content suggesting a putative role in carotenoid accumulation pattern in summer squash fruit.

  15. Expression of gentisate 1,2-dioxygenase (gdoA) genes involved in aromatic degradation in two haloarchaeal genera.

    Science.gov (United States)

    Fairley, D J; Wang, G; Rensing, C; Pepper, I L; Larkin, M J

    2006-12-01

    Gentisate-1,2-dioxygenase genes (gdoA), with homology to a number of bacterial dioxygenases, and genes encoding a putative coenzyme A (CoA)-synthetase subunit (acdB) and a CoA-thioesterase (tieA) were identified in two haloarchaeal isolates. In Haloarcula sp. D1, gdoA was expressed during growth on 4-hydroxybenzoate but not benzoate, and acdB and tieA were not expressed during growth on any of the aromatic substrates tested. In contrast, gdoA was expressed in Haloferax sp. D1227 during growth on benzoate, 3-hydroxybenzoate, cinnamate and phenylpropionate, and both acdB and tieA were expressed during growth on benzoate, cinnamate and phenylpropionate, but not on 3-hydroxybenzoate. This pattern of induction is consistent with these genes encoding steps in a CoA-mediated benzoate pathway in this strain.

  16. Cloning and characterization of the promoter of the 9-cis-epoxycarotenoid dioxygenase gene in Arachis hypogaea L.

    Science.gov (United States)

    Liang, Jianhua; Yang, Lixia; Chen, Xiong; Li, Ling; Guo, Dongliang; Li, Haihang; Zhang, Biyu

    2009-09-01

    We cloned the promoter of the 9-cis-epoxycarotenoid dioxygenase gene from Arachis hypogaea L. beta-Glucuronidase (GUS) histochemical staining and GUS activity assay indicated that the activity of the promoter was exhibited predominantly in the leaves and enhanced by water and NaCl stresses, and by application of abscisic acid (ABA) and salicylic acid (SA) in transgenic Arabidopsis. Moreover, two novel ABRE-like (abscisic acid response element) elements were identified in the promoter region.

  17. Loss-of-Function Mutation in the Dioxygenase-Encoding FTO Gene Causes Severe Growth Retardation and Multiple Malformations

    Science.gov (United States)

    Boissel, Sarah; Reish, Orit; Proulx, Karine; Kawagoe-Takaki, Hiroko; Sedgwick, Barbara; Yeo, Giles S.H.; Meyre, David; Golzio, Christelle; Molinari, Florence; Kadhom, Noman; Etchevers, Heather C.; Saudek, Vladimir; Farooqi, I. Sadaf; Froguel, Philippe; Lindahl, Tomas; O'Rahilly, Stephen; Munnich, Arnold; Colleaux, Laurence

    2009-01-01

    FTO is a nuclear protein belonging to the AlkB-related non-haem iron- and 2-oxoglutarate-dependent dioxygenase family. Although polymorphisms within the first intron of the FTO gene have been associated with obesity, the physiological role of FTO remains unknown. Here we show that a R316Q mutation, inactivating FTO enzymatic activity, is responsible for an autosomal-recessive lethal syndrome. Cultured skin fibroblasts from affected subjects showed impaired proliferation and accelerated senescence. These findings indicate that FTO is essential for normal development of the central nervous and cardiovascular systems in human and establish that a mutation in a human member of the AlkB-related dioxygenase family results in a severe polymalformation syndrome. PMID:19559399

  18. Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.

    Science.gov (United States)

    Beltrán-Valero de Bernabé, D; Granadino, B; Chiarelli, I; Porfirio, B; Mayatepek, E; Aquaron, R; Moore, M M; Festen, J J; Sanmartí, R; Peñalva, M A; de Córdoba, S R

    1998-01-01

    Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO); this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We cloned the human HGO gene and characterized two loss-of-function mutations, P230S and V300G, in the HGO gene in AKU patients. Here we report haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12 novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V) missense mutations that result in amino acid substitutions at positions conserved in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also report characterization of five polymorphic sites in HGO and describe the haplotypic associations of alleles at these sites in normal and AKU chromosomes. One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A, IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide substitutions (dimorphisms) have been detected; and c407T/A is a relatively frequent nucleotide substitution in the coding sequence, exon 4, resulting in an amino acid change (H80Q). These data provide insight into the origin and evolution of the various AKU alleles. PMID:9529363

  19. The FTO (fat mass and obesity associated gene codes for a novel member of the non-heme dioxygenase superfamily

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    Andrade-Navarro Miguel A

    2007-11-01

    Full Text Available Abstract Background Genetic variants in the FTO (fat mass and obesity associated gene have been associated with an increased risk of obesity. However, the function of its protein product has not been experimentally studied and previously reported sequence similarity analyses suggested the absence of homologs in existing protein databases. Here, we present the first detailed computational analysis of the sequence and predicted structure of the protein encoded by FTO. Results We performed a sequence similarity search using the human FTO protein as query and then generated a profile using the multiple sequence alignment of the homologous sequences. Profile-to-sequence and profile-to-profile based comparisons identified remote homologs of the non-heme dioxygenase family. Conclusion Our analysis suggests that human FTO is a member of the non-heme dioxygenase (Fe(II- and 2-oxoglutarate-dependent dioxygenases superfamily. Amino acid conservation patterns support this hypothesis and indicate that both 2-oxoglutarate and iron should be important for FTO function. This computational prediction of the function of FTO should suggest further steps for its experimental characterization and help to formulate hypothesis about the mechanisms by which it relates to obesity in humans.

  20. Stereospecific hydroxylation of indan by Escherichia coli containing the cloned toluene dioxygenase genes from Pseudomonas putida F1.

    Science.gov (United States)

    Brand, J M; Cruden, D L; Zylstra, G J; Gibson, D T

    1992-01-01

    Escherichia coli JM109(pDTG601), containing the todC1C2BA genes encoding toluene dioxygenase from Pseudomonas putida F1, oxidizes indan to (-)-(1R)-indanol (83% R) and trans-1,3-indandiol. Under similar conditions, P. putida F39/D oxidizes indan to (-)-(1R)-indanol (96% R), 1-indanone, and trans-1,3-indandiol. The differences in the enantiomeric composition of the 1-indanols formed by the two organisms are due to the presence of a 1-indanol dehydrogenase in P. putida F39/D that preferentially oxidizes (+)-(1S)-indanol. PMID:1444374

  1. Hybrid pseudomonads engineered by two-step homologous recombination acquire novel degradation abilities toward aromatics and polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Suenaga, Hikaru [National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan). Bioproduction Research Inst.; Nonaka, Kazuhiko; Goto, Masatoshi [Kyushu Univ., Fukuoka (Japan). Dept. of Bioscience and Biotechnology; Fujihara, Hidehiko; Furukawa, Kensuke [Beppu Univ. (Japan). Dept. of Fermentation and Food Science

    2010-10-15

    Pseudomonas pseudoalcaligenes KF707 possesses a chromosomally encoded bph gene cluster responsible for the catabolism of biphenyl and polychlorinated biphenyls. Previously, we constructed chimeric versions of the bphA1 gene, which encodes a large subunit of biphenyl dioxygenase, by using DNA shuffling between bphA1 genes from P. pseudoalcaligenes KF707 and Burkholderia xenovorans LB400. In this study, we demonstrate replacement of the bphA1 gene with chimeric bphA1 sequence within the chromosomal bph gene cluster by two-step homologous recombination. Notably, some of the hybrid strains acquired enhanced and/or expanded degradation capabilities for specific aromatic compounds, including single aromatic hydrocarbons and polychlorinated biphenyls. (orig.)

  2. In situ, real-time catabolic gene expression: Extraction and characterization of naphthalene dioxygenase mRNA transcripts from groundwater

    International Nuclear Information System (INIS)

    Wilson, M.S.; Bakermans, C.; Madsen, E.L.

    1999-01-01

    The authors developed procedures for isolating and characterizing in situ-transcribed mRNA from groundwater microorganisms catabolizing naphthalene at a coal tar waste-contaminated site. Groundwater was pumped through 0.22-microm-pore-size filters, which were then frozen to dry ice-ethanol. RNA was extracted from the frozen filters by boiling sodium dodecyl sulfate lysis and acidic phenol-chloroform extraction. Transcript characterization was performed with a series of PCR primers designed to amplify nahAc homologs. Several primer pairs were found to amplify nahAc homologs representing the entire diversity of the naphthalene-degrading genes. The environmental RNA extract was reverse transcribed, and the resultant mixture of cDNAs was amplified by PCR. A digoxigenin-labeled probe mixture was produced by PCR amplification of groundwater cDNA. This probe mixture hybridized under stringent conditions with the corresponding PCR products from naphthalene-degrading bacteria carrying a variety of nahAc homologs, indicating that diverse dioxygenase transcripts had been retrieved from groundwater. Diluted and undiluted cDNA preparations were independently amplified, and 28 of the resulting PCR products were cloned and sequenced. Sequence comparisons revealed two major groups related to the dioxygenase genes ndoB and dntAc, previously cloned from Pseudomonas putida NCIB 9816-4 and Burkholderia sp. strain DNT, respectively. A distinctive subgroup of sequences was found only in experiments performed with the undiluted cDNA preparation. To the authors' knowledge, these results are the first to directly document in situ transcription of genes encoding naphthalene catabolism at a contaminated site by indigenous microorganisms. The retrieved sequences represent greater diversity than has been detected at the study site by culture-based approaches

  3. Biphenyl-metabolizing bacteria in the rhizosphere of horseradish and bulk soil contaminated by polychlorinated biphenyls as revealed by stable isotope probing.

    Science.gov (United States)

    Uhlik, Ondrej; Jecna, Katerina; Mackova, Martina; Vlcek, Cestmir; Hroudova, Miluse; Demnerova, Katerina; Paces, Vaclav; Macek, Tomas

    2009-10-01

    DNA-based stable isotope probing in combination with terminal restriction fragment length polymorphism was used in order to identify members of the microbial community that metabolize biphenyl in the rhizosphere of horseradish (Armoracia rusticana) cultivated in soil contaminated with polychlorinated biphenyls (PCBs) compared to members of the microbial community in initial, uncultivated bulk soil. On the basis of early and recurrent detection of their 16S rRNA genes in clone libraries constructed from [(13)C]DNA, Hydrogenophaga spp. appeared to dominate biphenyl catabolism in the horseradish rhizosphere soil, whereas Paenibacillus spp. were the predominant biphenyl-utilizing bacteria in the initial bulk soil. Other bacteria found to derive carbon from biphenyl in this nutrient-amended microcosm-based study belonged mostly to the class Betaproteobacteria and were identified as Achromobacter spp., Variovorax spp., Methylovorus spp., or Methylophilus spp. Some bacteria that were unclassified at the genus level were also detected, and these bacteria may be members of undescribed genera. The deduced amino acid sequences of the biphenyl dioxygenase alpha subunits (BphA) from bacteria that incorporated [(13)C]into DNA in 3-day incubations of the soils with [(13)C]biphenyl are almost identical to that of Pseudomonas alcaligenes B-357. This suggests that the spectrum of the PCB congeners that can be degraded by these enzymes may be similar to that of strain B-357. These results demonstrate that altering the soil environment can result in the participation of different bacteria in the metabolism of biphenyl.

  4. Two novel mutations in the homogentisate-1,2-dioxygenase gene identified in Chinese Han Child with Alkaptonuria.

    Science.gov (United States)

    Li, Hongying; Zhang, Kaihui; Xu, Qun; Ma, Lixia; Lv, Xin; Sun, Ruopeng

    2015-03-01

    Alkaptonuria (AKU) is an autosomal recessive disorder of tyrosine metabolism, which is caused by a defect in the enzyme homogentisate 1,2-dioxygenase (HGD) with subsequent accumulation of homogentisic acid. Presently, more than 100 HGD mutations have been identified as the cause of the inborn error of metabolism across different populations worldwide. However, the HGD mutation is very rarely reported in Asia, especially China. In this study, we present mutational analyses of HGD gene in one Chinese Han child with AKU, which had been identified by gas chromatography-mass spectrometry detection of organic acids in urine samples. PCR and DNA sequencing of the entire coding region as well as exon-intron boundaries of HGD have been performed. Two novel mutations were identified in the HGD gene in this AKU case, a frameshift mutation of c.115delG in exon 3 and the splicing mutation of IVS5+3 A>C, a donor splice site of the exon 5 and exon-intron junction. The identification of these mutations in this study further expands the spectrum of known HGD gene mutations and contributes to prenatal molecular diagnosis of AKU.

  5. First report of a deletion encompassing an entire exon in the homogentisate 1,2-dioxygenase gene causing alkaptonuria.

    Science.gov (United States)

    Zouheir Habbal, Mohammad; Bou-Assi, Tarek; Zhu, Jun; Owen, Renius; Chehab, Farid F

    2014-01-01

    Alkaptonuria is often diagnosed clinically with episodes of dark urine, biochemically by the accumulation of peripheral homogentisic acid and molecularly by the presence of mutations in the homogentisate 1,2-dioxygenase gene (HGD). Alkaptonuria is invariably associated with HGD mutations, which consist of single nucleotide variants and small insertions/deletions. Surprisingly, the presence of deletions beyond a few nucleotides among over 150 reported deleterious mutations has not been described, raising the suspicion that this gene might be protected against the detrimental mechanisms of gene rearrangements. The quest for an HGD mutation in a proband with AKU revealed with a SNP array five large regions of homozygosity (5-16 Mb), one of which includes the HGD gene. A homozygous deletion of 649 bp deletion that encompasses the 72 nucleotides of exon 2 and surrounding DNA sequences in flanking introns of the HGD gene was unveiled in a proband with AKU. The nature of this deletion suggests that this in-frame deletion could generate a protein without exon 2. Thus, we modeled the tertiary structure of the mutant protein structure to determine the effect of exon 2 deletion. While the two β-pleated sheets encoded by exon 2 were missing in the mutant structure, other β-pleated sheets are largely unaffected by the deletion. However, nine novel α-helical coils substituted the eight coils present in the native HGD crystal structure. Thus, this deletion results in a deleterious enzyme, which is consistent with the proband's phenotype. Screening for mutations in the HGD gene, particularly in the Middle East, ought to include this exon 2 deletion in order to determine its frequency and uncover its origin.

  6. First report of a deletion encompassing an entire exon in the homogentisate 1,2-dioxygenase gene causing alkaptonuria.

    Directory of Open Access Journals (Sweden)

    Mohammad Zouheir Habbal

    Full Text Available Alkaptonuria is often diagnosed clinically with episodes of dark urine, biochemically by the accumulation of peripheral homogentisic acid and molecularly by the presence of mutations in the homogentisate 1,2-dioxygenase gene (HGD. Alkaptonuria is invariably associated with HGD mutations, which consist of single nucleotide variants and small insertions/deletions. Surprisingly, the presence of deletions beyond a few nucleotides among over 150 reported deleterious mutations has not been described, raising the suspicion that this gene might be protected against the detrimental mechanisms of gene rearrangements. The quest for an HGD mutation in a proband with AKU revealed with a SNP array five large regions of homozygosity (5-16 Mb, one of which includes the HGD gene. A homozygous deletion of 649 bp deletion that encompasses the 72 nucleotides of exon 2 and surrounding DNA sequences in flanking introns of the HGD gene was unveiled in a proband with AKU. The nature of this deletion suggests that this in-frame deletion could generate a protein without exon 2. Thus, we modeled the tertiary structure of the mutant protein structure to determine the effect of exon 2 deletion. While the two β-pleated sheets encoded by exon 2 were missing in the mutant structure, other β-pleated sheets are largely unaffected by the deletion. However, nine novel α-helical coils substituted the eight coils present in the native HGD crystal structure. Thus, this deletion results in a deleterious enzyme, which is consistent with the proband's phenotype. Screening for mutations in the HGD gene, particularly in the Middle East, ought to include this exon 2 deletion in order to determine its frequency and uncover its origin.

  7. Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1 Gene in Primary Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Naoko Minatani

    Full Text Available Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1 gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004. Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007. Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer.

  8. Disruption of a CAROTENOID CLEAVAGE DIOXYGENASE 4 gene converts flower colour from white to yellow in Brassica species.

    Science.gov (United States)

    Zhang, Bao; Liu, Chao; Wang, Yaqin; Yao, Xuan; Wang, Fang; Wu, Jiangsheng; King, Graham J; Liu, Kede

    2015-06-01

    In Brassica napus, yellow petals had a much higher content of carotenoids than white petals present in a small number of lines, with violaxanthin identified as the major carotenoid compound in yellow petals of rapeseed lines. Using positional cloning we identified a carotenoid cleavage dioxygenase 4 gene, BnaC3.CCD4, responsible for the formation of flower colour, with preferential expression in petals of white-flowered B. napus lines. Insertion of a CACTA-like transposable element 1 (TE1) into the coding region of BnaC3.CCD4 had disrupted its expression in yellow-flowered rapeseed lines. α-Ionone was identified as the major volatile apocarotenoid released from white petals but not from yellow petals. We speculate that BnaC3.CCD4 may use δ- and/or α-carotene as substrates. Four variations, including two CACTA-like TEs (alleles M1 and M4) and two insertion/deletions (INDELs, alleles M2 and M3), were identified in yellow-flowered Brassica oleracea lines. The two CACTA-like TEs were also identified in the coding region of BcaC3.CCD4 in Brassica carinata. However, the two INDELs were not detected in B. napus and B. carinata. We demonstrate that the insertions of TEs in BolC3.CCD4 predated the formation of the two allotetraploids. © 2015 The Authors New Phytologist © 2015 New Phytologist Trust.

  9. Identification and characterization of genes encoding polycyclic aromatic hydrocarbon dioxygenase and polycyclic aromatic hydrocarbon dihydrodiol dehydrogenase in Pseudomonas putida OUS82.

    OpenAIRE

    Takizawa, N; Kaida, N; Torigoe, S; Moritani, T; Sawada, T; Satoh, S; Kiyohara, H

    1994-01-01

    Naphthalene and phenanthrene are transformed by enzymes encoded by the pah gene cluster of Pseudomonas putida OUS82. The pahA and pahB genes, which encode the first and second enzymes, dioxygenase and cis-dihydrodiol dehydrogenase, respectively, were identified and sequenced. The DNA sequences showed that pahA and pahB were clustered and that pahA consisted of four cistrons, pahAa, pahAb, pahAc, and pahAd, which encode ferredoxin reductase, ferredoxin, and two subunits of the iron-sulfur prot...

  10. Effects of polycyclic aromatic hydrocarbons on microbial community structure and PAH ring hydroxylating dioxygenase gene abundance in soil.

    Science.gov (United States)

    Sawulski, Przemyslaw; Clipson, Nicholas; Doyle, Evelyn

    2014-11-01

    Development of successful bioremediation strategies for environments contaminated with recalcitrant pollutants requires in-depth knowledge of the microorganisms and microbial processes involved in degradation. The response of soil microbial communities to three polycyclic aromatic hydrocarbons, phenanthrene (3-ring), fluoranthene (4-ring) and benzo(a)pyrene (5-ring), was examined. Profiles of bacterial, archaeal and fungal communities were generated using molecular fingerprinting techniques (TRFLP, ARISA) and multivariate statistical tools were employed to interpret the effect of PAHs on community dynamics and composition. The extent and rate of PAH removal was directly related to the chemical structure, with the 5-ring PAH benzo(a)pyrene degraded more slowly than phenathrene or fluoranthene. Bacterial, archaeal and fungal communities were all significantly affected by PAH amendment, time and their interaction. Based on analysis of clone libraries, Actinobacteria appeared to dominate in fluoranthene amended soil, although they also represented a significant portion of the diversity in phenanthrene amended and unamended soils. In addition there appeared to be more γ-Proteobacteria and less Bacteroidetes in soil amended with either PAH compared to the control. The soil bacterial community clearly possessed the potential to degrade PAHs as evidenced by the abundance of PAH ring hydroxylating (PAH-RHDα) genes from both gram negative (GN) and gram positive (GP) bacteria in PAH-amended and control soils. Although the dioxygenase gene from GP bacteria was less abundant in soil than the gene associated with GN bacteria, significant (p PAH-RHDα gene were observed during phenanthrene and fluoranthene degradation, whereas there was no significant difference in the abundance of the GN PAH-RHDα gene during the course of the experiment. Few studies to-date have examined the effect of pollutants on more than one microbial community in soil. The current study provides

  11. Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder.

    Science.gov (United States)

    Cutler, Jessica A; Rush, A John; McMahon, Francis J; Laje, Gonzalo

    2012-03-01

    The essential amino acid tryptophan is the precursor to serotonin, but it can also be metabolized into kynurenine through indoleamine-2,3-dioxygenase (IDO). Increased immune activation has long been associated with symptoms of depression and has been shown to upregulate the expression of IDO. The presence of additional IDO directs more tryptophan down the kynurenine pathway, leaving less available for synthesis of serotonin and its metabolites. Kynurenine can be metabolized through a series of enzymes to quinolinic acid, a potent N-methyl-D-aspartate receptor agonist with demonstrated neurotoxic effects. We tested the hypothesis that IDO plays a role in outcome of treatment with the selective serotonin reuptake inhibitor, citalopram. Patients consisted of 1953 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Genotypes corresponding to 94 single nucleotide polymorphisms (SNPs) in the genes IDO1 and IDO2, which encode IDO and IDO2, were extracted from a larger genome-wide set and analyzed using single marker tests to look for association with previously defined response, remission and QIDS-C score change phenotypes, with adequate correction for racial stratification and multiple testing. One SNP, rs2929115, showed evidence of association with citalopram response (OR = 0.64, p = 0.0005) after experiment-wide correction for multiple testing. Another closely associated marker, rs2929116 (OR = 0.64, p = 0.0006) had an experiment-wide significant result. Both implicated SNPs are located between 26 kb and 28 kb downstream of IDO2. We conclude that common genetic variation in IDO1 and IDO2 may play a role in antidepressant treatment outcome. These results are modest in a genome-wide context and need to be replicated in an independent sample.

  12. Abundance of dioxygenase genes similar to Ralstonia sp strain U2 nagAc is correlated with naphthalene concentrations in coal tar-contaminated freshwater sediments

    Energy Technology Data Exchange (ETDEWEB)

    Dionisi, H.M.; Chewning, C.S.; Morgan, K.H.; Menn, F.M.; Easter, J.P; Sayler, G.S. [University of Tennessee, Knoxville, TN (United States). Center for Environmental Biotechnology

    2004-07-01

    We designed a real-time PCR assay able to recognize dioxygenase large-subunit gene sequences with more than 90% similarity to the Ralstonia sp. strain U2 nagAc gene (nagAc-like gene sequences) in order to study the importance of organisms carrying these genes in the biodegradation of naphthalene. Sequencing of PCR products indicated that this real-time PCR assay was specific and able to detect a variety of nagAc-like gene sequences. One to 100 ng of contaminated-sediment total DNA in 25-{mu}l reaction mixtures produced an amplification efficiency of 0.97 without evident PCR inhibition. The assay was applied to surficial freshwater sediment samples obtained in or in close proximity to a coal tar-contaminated Superfund site. Naphthalene concentrations in the analyzed samples varied between 0.18 and 106 mg/kg of dry weight sediment. The assay for nagAc-like sequences indicated the presence of (4.1 {+-} 0.7) X 10{sup 3} to (2.9 {+-} 0.3) X 10{sup 5} copies of nagAc-like dioxygenase genes per mug of DNA extracted from sediment samples. These values corresponded to (1.2 {+-} 0.6) X 10{sup 5} to (5.4 {+-} 0.4) X 10{sup 7} copies of this target per g of dry weight sediment when losses of DNA during extraction were taken into account. There was a positive correlation between naphthalene concentrations and nagAc-like gene copies per microgram of DNA = 0.89) and per gram of dry weight sediment = 0.77). These results provide evidence of the ecological significance of organisms carrying nagAc-like genes in the biodegradation of naphthalene.

  13. OXIDATION OF BIPHENYL BY A MULTICOMPONENT ENZYME SYSTEM FROM PSEUDOMONAS SP. STRAIN LB400

    Science.gov (United States)

    Pseudomonas sp. strain LB400 grows on biphenyl as the sole carbon and energy source. This organism also cooxidizes several chlorinated biphenyl congeners. Biphenyl dioxygenase activity in cell extract required addition of NAD(P)H as an electron donor for the conversion of bipheny...

  14. Genome-Wide Analysis of the Biosynthesis and Deactivation of Gibberellin-Dioxygenases Gene Family in Camellia sinensis (L. O. Kuntze

    Directory of Open Access Journals (Sweden)

    Cheng Pan

    2017-09-01

    Full Text Available Gibberellins (GAs, a class of diterpenoid phytohormones, play a key role in regulating diverse processes throughout the life cycle of plants. Bioactive GA levels are rapidly regulated by Gibberellin-dioxygenases (GAox, which are involved in the biosynthesis and deactivation of gibberellin. In this manuscript, a comprehensive genome-wide analysis was carried out to find all GAox in Camellia sinensis. For the first time in a tea plant, 14 CsGAox genes, containing two domains, DIOX_N (PF14226 and 2OG-FeII_Oxy, were identified (PF03171. These genes all belong to 2-oxoglutarate-dependent dioxygenases (2-ODD, including four CsGA20ox (EC: 1.14.11.12, three CsGA3ox (EC: 1.14.11.15, and seven CsGA2ox (EC: 1.14.11.13. According to the phylogenetic classification as in Arabidopsis, the CsGAox genes spanned five subgroups. Each CsGAox shows tissue-specific expression patterns, although these vary greatly. Some candidate genes, which may play an important role in response to external abiotic stresses, have been identified with regards to patterns, such as CsGA20ox2, CsGA3ox2, CsGA3ox3, CsGA2ox1, CsGA2ox2, and CsGA2ox4. The bioactive GA levels may be closely related to the GA20ox, GA3ox and GA2ox genes. In addition, the candidate genes could be used as marker genes for abiotic stress resistance breeding in tea plants.

  15. Biphenyl-Metabolizing Bacteria in the Rhizosphere of Horseradish and Bulk Soil Contaminated by Polychlorinated Biphenyls as Revealed by Stable Isotope Probing▿ †

    Science.gov (United States)

    Uhlik, Ondrej; Jecna, Katerina; Mackova, Martina; Vlcek, Cestmir; Hroudova, Miluse; Demnerova, Katerina; Paces, Vaclav; Macek, Tomas

    2009-01-01

    DNA-based stable isotope probing in combination with terminal restriction fragment length polymorphism was used in order to identify members of the microbial community that metabolize biphenyl in the rhizosphere of horseradish (Armoracia rusticana) cultivated in soil contaminated with polychlorinated biphenyls (PCBs) compared to members of the microbial community in initial, uncultivated bulk soil. On the basis of early and recurrent detection of their 16S rRNA genes in clone libraries constructed from [13C]DNA, Hydrogenophaga spp. appeared to dominate biphenyl catabolism in the horseradish rhizosphere soil, whereas Paenibacillus spp. were the predominant biphenyl-utilizing bacteria in the initial bulk soil. Other bacteria found to derive carbon from biphenyl in this nutrient-amended microcosm-based study belonged mostly to the class Betaproteobacteria and were identified as Achromobacter spp., Variovorax spp., Methylovorus spp., or Methylophilus spp. Some bacteria that were unclassified at the genus level were also detected, and these bacteria may be members of undescribed genera. The deduced amino acid sequences of the biphenyl dioxygenase α subunits (BphA) from bacteria that incorporated [13C]into DNA in 3-day incubations of the soils with [13C]biphenyl are almost identical to that of Pseudomonas alcaligenes B-357. This suggests that the spectrum of the PCB congeners that can be degraded by these enzymes may be similar to that of strain B-357. These results demonstrate that altering the soil environment can result in the participation of different bacteria in the metabolism of biphenyl. PMID:19700551

  16. Characterization of the Promoter Region of an Arabidopsis Gene for 9-cis-Epoxycarotenoid Dioxygenase Involved in Dehydration-Inducible Transcription

    Science.gov (United States)

    Behnam, Babak; Iuchi, Satoshi; Fujita, Miki; Fujita, Yasunari; Takasaki, Hironori; Osakabe, Yuriko; Yamaguchi-Shinozaki, Kazuko; Kobayashi, Masatomo; Shinozaki, Kazuo

    2013-01-01

    Plants respond to dehydration stress and tolerate water-deficit status through complex physiological and cellular processes. Many genes are induced by water deficit. Abscisic acid (ABA) plays important roles in tolerance to dehydration stress by inducing many stress genes. ABA is synthesized de novo in response to dehydration. Most of the genes involved in ABA biosynthesis have been identified, and they are expressed mainly in leaf vascular tissues. Of the products of such genes, 9-cis-epoxycarotenoid dioxygenase (NCED) is a key enzyme in ABA biosynthesis. One of the five NCED genes in Arabidopsis, AtNCED3, is significantly induced by dehydration. To understand the regulatory mechanism of the early stages of the dehydration stress response, it is important to analyse the transcriptional regulatory systems of AtNCED3. In the present study, we found that an overlapping G-box recognition sequence (5′-CACGTG-3′) at −2248 bp from the transcriptional start site of AtNCED3 is an important cis-acting element in the induction of the dehydration response. We discuss the possible transcriptional regulatory system of dehydration-responsive AtNCED3 expression, and how this may control the level of ABA under water-deficit conditions. PMID:23604098

  17. Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene (HGO).

    Science.gov (United States)

    Beltrán-Valero de Bernabé, D; Jimenez, F J; Aquaron, R; Rodríguez de Córdoba, S

    1999-01-01

    We recently showed that alkaptonuria (AKU) is caused by loss-of-function mutations in the homogentisate 1,2 dioxygenase gene (HGO). Herein we describe haplotype and mutational analyses of HGO in seven new AKU pedigrees. These analyses identified two novel single-nucleotide polymorphisms (INV4+31A-->G and INV11+18A-->G) and six novel AKU mutations (INV1-1G-->A, W60G, Y62C, A122D, P230T, and D291E), which further illustrates the remarkable allelic heterogeneity found in AKU. Reexamination of all 29 mutations and polymorphisms thus far described in HGO shows that these nucleotide changes are not randomly distributed; the CCC sequence motif and its inverted complement, GGG, are preferentially mutated. These analyses also demonstrated that the nucleotide substitutions in HGO do not involve CpG dinucleotides, which illustrates important differences between HGO and other genes for the occurrence of mutation at specific short-sequence motifs. Because the CCC sequence motifs comprise a significant proportion (34.5%) of all mutated bases that have been observed in HGO, we conclude that the CCC triplet is a mutational hot spot in HGO. PMID:10205262

  18. A "White" Anthocyanin-less Pomegranate (Punica granatum L.) Caused by an Insertion in the Coding Region of the Leucoanthocyanidin Dioxygenase (LDOX; ANS) Gene.

    Science.gov (United States)

    Ben-Simhon, Zohar; Judeinstein, Sylvie; Trainin, Taly; Harel-Beja, Rotem; Bar-Ya'akov, Irit; Borochov-Neori, Hamutal; Holland, Doron

    2015-01-01

    Color is an important determinant of pomegranate fruit quality and commercial value. To understand the genetic factors controlling color in pomegranate, chemical, molecular and genetic characterization of a "white" pomegranate was performed. This unique accession is lacking the typical pomegranate color rendered by anthocyanins in all tissues of the plant, including flowers, fruit (skin and arils) and leaves. Steady-state gene-expression analysis indicated that none of the analyzed "white" pomegranate tissues are able to synthesize mRNA corresponding to the PgLDOX gene (leucoanthocyanidin dioxygenase, also called ANS, anthocyanidin synthase), which is one of the central structural genes in the anthocyanin-biosynthesis pathway. HPLC analysis revealed that none of the "white" pomegranate tissues accumulate anthocyanins, whereas other flavonoids, corresponding to biochemical reactions upstream of LDOX, were present. Molecular analysis of the "white" pomegranate revealed the presence of an insertion and an SNP within the coding region of PgLDOX. It was found that the SNP does not change amino acid sequence and is not fully linked with the "white" phenotype in all pomegranate accessions from the collection. On the other hand, genotyping of pomegranate accessions from the collection and segregating populations for the "white" phenotype demonstrated its complete linkage with the insertion, inherited as a recessive single-gene trait. Taken together, the results indicate that the insertion in PgLDOX is responsible for the "white" anthocyanin-less phenotype. These data provide the first direct molecular, genetic and chemical evidence for the effect of a natural modification in the LDOX gene on color accumulation in a fruit-bearing woody perennial deciduous tree. This modification can be further utilized to elucidate the physiological role of anthocyanins in protecting the tree organs from harmful environmental conditions, such as temperature and UV radiation.

  19. Cloning and functional analysis of 9-cis-epoxycarotenoid dioxygenase (NCED) genes encoding a key enzyme during abscisic acid biosynthesis from peach and grape fruits.

    Science.gov (United States)

    Zhang, Mei; Leng, Ping; Zhang, Guanglian; Li, Xiangxin

    2009-08-15

    Ripening and senescence are generally controlled by ethylene in climacteric fruits like peaches, and the ripening process of grape, a non-climacteric fruit, may have some relationship to abscisic acid (ABA) function. In order to better understand the role of ABA in ripening and senescence of these two types of fruits, we cloned the 9-cis-epoxycarotenoid dioxygenase (NCED) gene that encodes a key enzyme in ABA biosynthesis from peaches and grapes using an RT-PCR approach. The NCED gene fragments were cloned from peaches (PpNCED1and PpNCED2, each 740bp) and grapes (VVNCED1, 741bp) using degenerate primers designed based on the conserved amino acids sequence of NCEDs in other plants. PpNCED1 showed 78.54% homology with PpNCED2, 74.90% homology with VVNCED1, and both showed high homology to NCEDs from other plants. The expression patterns of PpNCED1 and VVNCED1 were very similar. Both were highly expressed at the beginning of ripening when ABA content becomes high. The maximum ABA preceded ethylene production in peach fruit. ABA in the grape gradually increased from the beginning of ripening and reached the highest level at 20d before the harvest stage. However, ethylene remained at low levels during the entire process of fruit development, including ripening and senescence. ABA content, and ripening and softening of both types of fruits, were promoted or delayed by exogenous ABA or Fluridone (or NDGA) treatment. The roles of ABA and ethylene in the later ripening of fruit are complex. Based on results obtained in this study, we concluded that PpNCED1 and VVNCED1 initiate ABA biosynthesis at the beginning of fruit ripening, and that ABA accumulation might play a key role in the regulation of ripeness and senescence of both peach and grape fruits.

  20. Cloning and characterization of two 9-cis-epoxycarotenoid dioxygenase genes, differentially regulated during fruit maturation and under stress conditions, from orange (Citrus sinensis L. Osbeck).

    Science.gov (United States)

    Rodrigo, María-Jesús; Alquezar, Berta; Zacarías, Lorenzo

    2006-01-01

    There is now biochemical and genetic evidence that oxidative cleavage of cis-epoxycarotenoids by 9-cis-epoxycarotenoid dioxygenase (NCED) is the critical step in the regulation of abscisic acid (ABA) synthesis in higher plants. The peel of Citrus fruit accumulates large amounts of ABA during maturation. To understand the regulation of ABA biosynthesis in Citrus, two full-length cDNAs (CsNCED1 and CsNCED2) encoding NCEDs were isolated and characterized from the epicarp of orange fruits (Citrus sinensis L. Osbeck). Expression of the CsNCED1 gene increased in the epicarp during natural and ethylene-induced fruit maturation, and in water-stressed leaves, in a pattern consistent with the accumulation of ABA. The second gene, CsNCED2, was not detected in dehydrated leaves and, in fruits, exhibited a differential expression to that of CsNCED1. Taken together, these results suggests that CsNCED1 is likely to play a primary role in the biosynthesis of ABA in both leaves and fruits, while CsNCED2 appears to play a subsidiary role restricted to chromoplast-containing tissue. Furthermore, analysis of 9-cis-violaxanthin and 9'-cis-neoxanthin, as the two possible substrates for NCEDs, revealed that the former was the main carotenoid in the outer coloured part of the fruit peel as the fruit ripened or after ethylene treatment, whereas 9'-cis-neoxanthin was not detected or was in trace amounts. By contrast, turgid and dehydrated leaves contained 9'-cis-neoxanthin but 9-cis-violaxanthin was absent. Based on these results, it is suggested that 9-cis-violaxanthin may be the predominant substrate for NCED in the peel of Citrus fruits, whereas 9'-cis-neoxanthin would be the precursor of ABA in photosynthetic tissues.

  1. Gene silencing of indoleamine 2,3-dioxygenase 2 in melanoma cells induces apoptosis through the suppression of NAD+ and inhibits in vivo tumor growth.

    Science.gov (United States)

    Liu, Yanling; Zhang, Yujuan; Zheng, Xiufen; Zhang, Xusheng; Wang, Hongmei; Li, Qin; Yuan, Keng; Zhou, Nanjing; Yu, Yanrong; Song, Na; Fu, Jiamin; Min, Weiping

    2016-05-31

    Indoleamine 2,3-dioxygenase 2 (IDO2) is a newly discovered enzyme that catalyzes the initial and rate-limiting step in the degradation of tryptophan. As a homologous protein of IDO1, IDO2 plays an inhibitory role in T cell proliferation, and it is essential for regulatory T cell (Treg) generation in healthy conditions. Little is known about the immune-independent functions of IDO2 relevant to its specific contributions to physiology and pathophysiology in cancer cells. The purpose of this study was to assess the impact of IDO2 gene silencing as a way to inhibit B16-BL6 cancer cells in a murine model. Here, for the first time, we show that knockdown of IDO2 using small interfering RNA (siRNA) inhibits cancer cell proliferation, arrests cell cycle in G1, induces greater cell apoptosis, and reduces cell migration in vitro. Knockdown of IDO2 decreased the generation of nicotinamide adenine dinucleotide (NAD+) while increasing the generation of reactive oxygen species (ROS). We further demonstrate that cell apoptosis, induced by IDO2 downregulation, can be weakened by addition of exogenous NAD+, suggesting a novel mechanism by which IDO2 promotes tumor growth through its metabolite product NAD+. In addition to in vitro findings, we also demonstrate that IDO2 silencing in tumor cells using short hairpin RNA (shRNA) delayed tumor formation and arrested tumor growth in vivo. In conclusion, this study demonstrates a new non-immune-associated mechanism of IDO2 in vitro and IDO2 expression in B16-BL6 cells contributes to cancer development and progression. Our research provides evidence of a novel target for gene silencing that has the potential to enhance cancer therapy.

  2. Transgenic plants to improve rhizoremediation of polychlorinated biphenyls (PCBs)

    Czech Academy of Sciences Publication Activity Database

    Sylvestre, M.; Macek, Tomáš; Macková, Martina

    2009-01-01

    Roč. 20, č. 2 (2009), s. 242-247 ISSN 0958-1669 R&D Projects: GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z40550506 Keywords : bacterial dioxygenases * GM- plants * polychlorinated biphenyls * rhizoremediation Subject RIV: EI - Biotechnology ; Bionics Impact factor: 7.820, year: 2009

  3. Characterization of arene di-oxygenases involved in polycyclic aromatic hydrocarbons biodegradation in Mycobacterium sp. 6PY1; Caracterisation d'arene dioxygenases impliquees dans la biodegradation des hydrocarbures aromatiques polycycliques chez Mycobacterium sp. 6PY1

    Energy Technology Data Exchange (ETDEWEB)

    Kuony, S.

    2005-06-15

    This thesis deals with the bacterial biodegradation of pollutants called polycyclic aromatic hydrocarbons (PAHs). The bacterium Mycobacterium sp. 6PY1 was isolated from a polluted soil for its ability to use pyrene, a 4-ring PAH, as sole source of carbon and energy. To learn about the pyrene metabolic pathway, the identification of the enzymes involved in this process has been undertaken using a proteomic approach. This approach revealed the occurrence of two ring-hydroxylating di-oxygenases in strain 6PY1, which could catalyze the initial attack of pyrene. The goal of this study was to clone the genes encoding the di-oxygenases identified in Mycobacterium sp. 6PY1, over-express these genes in an heterologous system in order to facilitate the purification of the corresponding enzymes, and determine the biochemical and catalytic properties of these enzymes. The pdoA1B1 genes encoding the terminal component of a di-oxygenase were cloned and over-expressed in Escherichia coli. The catalytic properties of this enzyme, called Pdo1, were determined in vivo by measuring the oxidation products of 2- to 4-ring PAHs by gas chromatography coupled to mass spectrometry (GC-MS). Analysis of the selectivity of the enzyme, as determined using GC-MS, showed that Pdo1 preferentially oxidized 3- or 4-ring PAHs, including phenanthrene and pyrene, but was inactive on di-aromatic compounds such as naphthalene and biphenyl. Pdo1 was unstable and was therefore purified in inactive form. The genes encoding a second di-oxygenase component were found in a locus containing two other catabolic genes. The pdoA2B2 genes encoded an enzyme called Pdo2 showing a narrow specificity towards 2- to 3-ring PAHs, and a high preference for phenanthrene. Pdo2 is an a3{beta}3 hexamer, containing [2Fe-2S] Rieske clusters which confer it a characteristic absorbance spectrum. A third set of genes possibly encoding another di-oxygenase was discovered in the genome of Mycobacterium sp. 6PY1. This set is closely

  4. Individual Polychlorinated Biphenyl (PCB) Congeners Produce Tissue- and Gene-Specific Effects on Thyroid Hormone Signaling during Development

    Science.gov (United States)

    Giera, Stefanie; Bansal, Ruby; Ortiz-Toro, Theresa M.; Taub, Daniel G.

    2011-01-01

    Polychlorinated biphenyls (PCB) are industrial chemicals linked to developmental deficits that may be caused in part by disrupting thyroid hormone (TH) action by either reducing serum TH or interacting directly with the TH receptor (TR). Individual PCB congeners can activate the TR in vitro when the metabolic enzyme cytochrome P4501A1 (CYP1A1) is induced, suggesting that specific PCB metabolites act as TR agonists. To test this hypothesis in vivo, we compared two combinations of PCB congeners that either activate the TR (PCB 105 and 118) or not (PCB 138 and 153) in the presence or absence of a PCB congener (PCB 126) that induces CYP1A1 in vitro. Aroclor 1254 was used as a positive control, and a group treated with propylthiouracil was included to characterize the effects of low serum TH. We monitored the effects on TH signaling in several peripheral tissues by measuring the mRNA expression of well-known TH-response genes in these tissues. Aroclor 1254 and its component PCB 105/118/126 reduced total T4 to the same extent as that of propylthiouracil but increased the expression of some TH target genes in liver. This effect was strongly correlated with CYP1A1 expression supporting the hypothesis that metabolism is necessary. Effects were gene and tissue specific, indicating that tissue-specific metabolism is an important component of PCB disruption of TH action and that PCB metabolites interact in complex ways with the TR. These are essential mechanisms to consider when evaluating the health risks of contaminant exposures, for both PCB and other polycyclic compounds known to interact with nuclear hormone receptors. PMID:21540284

  5. [Comparative study of aromatic ring meta-cleavage enzymes in Pseudomonas strains with plasmid and chromosomal genetic control of the catabolism of biphenyl and m-toluate].

    Science.gov (United States)

    Selifonov, S A; Starozoĭtov, I I

    1990-12-01

    It was shown that two different enzymes of aromatic ring oxidative meta-cleavage (2,3-dihydroxybiphenyl-1,2-dioxygenase), DBO and catechol-2,3-dioxygenase, C230) function in Pseudomonas strains with a plasmid and chromosomal genetic control of biphenyl and toluate catabolism. A comparative analysis of DBO's and C230's expressed by the pBS241 biphenyl degradative plasmid in P. putida BS893, pBS311 in P. putida U83, chromosomal genes in P. putida BF and C230 from P. putida PaW160 (pWWO) was carried out. It was found that the DBO's of all strains under study are highly specialized enzymes in respect of 2,3-dihydroxybiphenyl cleavage and are also able to cleave 3-methyl-catechol and catechol (but not 4-methylcatechol) at low rates. In contrast with DBO's, in Pseudomonas strains the substrate specificities of all C230's are variable. The C230's expressed by the D-plasmids pBS241 and pBC311 have a moderate affinity for catechol, 3-methyl- and 4-methylcatechol, but are unable to cleave 2,3-dihydroxybiphenyl. The C230 which is encoded by the chromosomal structure gene from P. putida BF is very similar to C230 which codes for the TOL-plasmid pWWO. These plasmid differ from C230's expressed by biphenyl D-plasmids due to their capability to cleave 2,3-dihydroxybiphenyl in addition to catechol cleavage. All DBO's and C230's under study possess a number of properties that are typical for the enzymes having an oxidative meta-cleaving effect. The different roles of these enzymes in biphenyl and toluate catabolism in Pseudomonas strains are discussed.

  6. Characterization of the Second LysR-Type Regulator in the Biphenyl-Catabolic Gene Cluster of Pseudomonas pseudoalcaligenes KF707

    OpenAIRE

    Watanabe, Takahito; Fujihara, Hidehiko; Furukawa, Kensuke

    2003-01-01

    Pseudomonas pseudoalcaligenes KF707 possesses a biphenyl-catabolic (bph) gene cluster consisting of bphR1A1A2-(orf3)-bphA3A4BCX0X1X2X3D. The bphR1 (formerly orf0) gene product, which belongs to the GntR family, is a positive regulator for itself and bphX0X1X2X3D. Further analysis in this study revealed that a second regulator belonging to the LysR family (designated bphR2) is involved in the regulation of the bph genes in KF707. The bphR2 gene was not located near the bph gene cluster, and it...

  7. Broad specificity dioxygenase enzymes and the bioremediation of hazardous aromatic pollutants

    International Nuclear Information System (INIS)

    Bonus, P.A.; Nies, L.

    1996-01-01

    The release of aromatic compounds to the environment is a major source of global pollution. In particular, the contamination of soil and groundwater with benzene, toluene, and xylenes (BTX) is the most ubiquitous form of aromatic pollution. The major source of BTX contamination is the release of gasoline and other petroleum products. This research focused on the improvement of bioremediation of BTX through a better understanding of broad specificity dioxygenase enzymes produced by soil and sediment bacteria. The investigation utilized pure bacterial strains isolated on biphenyl, naphthalene, or toluene. These isolated aerobic bacteria were then used to investigate the specificity of the initial enzymatic attack on aromatic compounds including BTX and polychlorinated biphenyls (PCBs). The enzymatic specificity and competency of the five isolates selected for study were determined through the use of growth tests and two rapid assay techniques. The growth tests were conducted on mineral agar plates or in liquid cultures, and they were used to determine substrate specificity. In addition, rapid assays for both BTX and PCBs were carried out using various growth substrates. These assays allowed further clarification of the specificity of the dioxygenase enzymes involved in aromatic degradation. Preliminary results of the PCB assay show that biphenyl and naphthalene isolated organisms grown on biphenyl, benzoate, naphthalene, and succinate maintain production of broad specificity dioxygenase enzymes able to degrade PCBs. Likewise, the BTX assay confirms that biphenyl and naphthalene selected organisms grown on their respective selection substrates completely degrade BTX including all three xylene isomers. In comparison, the toluene selected organism that was studied was unable to degrade PCBs, but it was able to degrade all BTX constituents

  8. Bioaugmentation of a historically contaminated soil by polychlorinated biphenyls with Lentinus tigrinus

    Directory of Open Access Journals (Sweden)

    Federici Ermanno

    2012-03-01

    Full Text Available Abstract Background Several species belonging to the ecological group of white-rot basidiomycetes are able to bring about the remediation of matrices contaminated by a large variety of anthropic organic pollutants. Among them, polychlorobiphenyls (PCBs are characterized by a high recalcitrance due to both their low bioavailability and the inability of natural microbial communities to degrade them at significant rates and extents. Objective of this study was to assess the impact of a maize stalk-immobilized Lentinus tigrinus CBS 577.79 inoculant combined with soybean oil (SO, as a possible PCB-mobilizing agent, on the bioremediation and resident microbiota of an actual Aroclor 1260 historically contaminated soil under unsaturated solid-phase conditions. Results Best overall PCB depletions (33.6 ± 0.3% and dechlorination (23.2 ± 1.3% were found after 60 d incubation in the absence of SO where, however, the fungus appeared to exert adverse effects on both the growth of biphenyl- and chlorobenzoate-degrading bacteria and the abundance of genes coding for both biphenyl dioxygenase (bph and catechol-2,3-dioxygenase. A significant (P bph. Conclusions The PCB depletion extents obtained in the presence of L. tigrinus are by far higher than those reported in other remediation studies conducted under unsaturated solid phase conditions on actual site soils historically contaminated by Aroclor 1260. These results suggest that the bioaugmentation strategy with the maize stalk-immobilized mycelium of this species might be promising in the reclamation of PCB-contaminated soils. The addition of SO to matrices contaminated by technical PCB mixtures, such as Aroclor 1242 and Delor 103 and characterized by a large preponderance of low chlorinated congeners, might not be advisable.

  9. 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...

  10. Polychlorinated biphenyl rhizoremediation by Pseudomonas fluorescens F113 derivatives, using a Sinorhizobium meliloti nod system to drive bph gene expression

    Czech Academy of Sciences Publication Activity Database

    Villacieros, M.; Whelan, C.; Macková, Martina; Molgaard, J.; Sánchez-Contreras, M.; Lloret, J.; Cárcer de, D.; Oruezábal, R. I.; Bolanos, L.; Macek, Tomáš; Karlson, U.; Dowling, D. N.; Martín, M.; Rivilla, R.

    2005-01-01

    Roč. 71, č. 5 (2005), 2687-2694 ISSN 0099-2240 Grant - others:5thFW(XE) QLK3-CT-2001-00101; European Commission(XE) BIO4-CT97-2227 Institutional research plan: CEZ:AV0Z4055905 Keywords : polychlorinated biphenyls * rhizoremediation Subject RIV: CC - Organic Chemistry Impact factor: 3.818, year: 2005

  11. Phytoremediation of Polychlorinated Biphenyls: New Trends and Promises

    Science.gov (United States)

    Van Aken, Benoit; Correa, Paola A.; Schnoor, Jerald L.

    2011-01-01

    Transgenic plants and associated bacteria constitute a new generation of genetically modified organisms for efficient and environmental-friendly treatment of soil and water contaminated with polychlorinated biphenyls (PCBs). This review focuses on recent advances in phytoremediation for the treatment of PCBs, including the development of transgenic plants and associated bacteria. Phytoremediation, or the use of higher plants for rehabilitation of soil and groundwater, is a promising strategy for cost-effective treatment of sites contaminated by toxic compounds, including toxic PCBs. Plants can help mitigate environmental pollution by PCBs through a range of mechanisms: besides uptake from soil (phytoextraction), plants are capable of enzymatic transformation of PCBs (phytotransformation); by releasing a variety of secondary metabolites, plants also enhance the microbial activity in the root zone, improving biodegradation of PCBs (rhizoremediation). However, because of their hydrophobicity and chemical stability, PCBs are only slowly taken up and degraded by plants and associated bacteria, resulting in incomplete treatment and potential release of toxic metabolites into the environment. Moreover, naturally occurring plant-associated bacteria may not possess the enzymatic machinery necessary for PCB degradation. In order to overcome these limitations, bacterial genes involved in the metabolism of PCBs, such as biphenyl dioxygenases, have been introduced into higher plants, following a strategy similar to the development of transgenic crops. Similarly, bacteria have then been genetically modified that exhibit improved biodegradation capabilities and are able to maintain stable relationships with plants. Transgenic plants and associated bacteria bring hope for a broader and more efficient application of phytoremediation for the treatment of PCBs. PMID:20384372

  12. Metabolism and Residues of 2,4-Dichlorophenoxyacetic Acid in DAS-40278-9 Maize (Zea mays) Transformed with Aryloxyalkanoate Dioxygenase-1 Gene.

    Science.gov (United States)

    Zhou, Xiao; Rotondaro, Sandra L; Ma, Mingming; Rosser, Steve W; Olberding, Ed L; Wendelburg, Brian M; Adelfinskaya, Yelena A; Balcer, Jesse L; Blewett, T Craig; Clements, Bruce

    2016-10-12

    DAS-40278-9 maize, which is developed by Dow AgroSciences, has been genetically modified to express the aryloxyalkanoate dioxygenase-1 (AAD-1) protein and is tolerant to phenoxy auxin herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D). To understand the metabolic route and residue distribution of 2,4-D in DAS-40278-9 maize, a metabolism study was conducted with 14 C-radiolabeled 2,4-D applied at the maximum seasonal rate. Plants were grown in boxes outdoors. Forage and mature grain, cobs, and stover were collected for analysis. The metabolism study showed that 2,4-D was metabolized to 2,4-dichlorophenol (2,4-DCP), which was then rapidly conjugated with glucose. Field-scale residue studies with 2,4-D applied at the maximum seasonal rate were conducted at 25 sites in the U.S. and Canada to measure the residues of 2,4-D and free and conjugated 2,4-DCP in mature forage, grain, and stover. Residues of 2,4-D were not detectable in the majority of the grain samples and averaged <1.0 and <1.5 μg/g in forage and stover, respectively. Free plus conjugated 2,4-DCP was not observed in grain and averaged <1.0 μg/g in forage and stover.

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

    Science.gov (United States)

    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 acetyltransferase assay we demonstrate here that the enhancer termed GSTP1 enhancer I (GPEI) is necessary for the stimulation by PenCB of GSTP1 gene expression in primary cultured rat liver parenchymal cells. GPEI is already known to contain a dyad of PMA responsive element-like elements oriented palindromically. It is suggested that a novel signal transduction pathway activated by PenCB contributes to the stimulation of GSTP1 expression. PMID:10051428

  14. Assay of cysteine dioxygenase activity

    International Nuclear Information System (INIS)

    Bagley, P.J.; Stipanuk, M.H.

    1990-01-01

    It has been proposed that rat liver contains two cysteine dioxygenase enzymes which convert cysteine to cysteinesulfinic acid, one which is stimulated by NAD + and has a pH optimum of 6.8 and one which is not stimulated by NAD + and has a pH optimum of 9.0. This led the authors to reinvestigate assay conditions for measuring cysteine dioxygenase activity in rat liver homogenate. An HPLC method, using an anion exchange column (Dionex Amino-Pac trademark PA1 (4x250 mm)) was used to separate the [ 35 S]cysteinesulfinic acid produced from [ 35 S]cysteine in the incubation mixture. They demonstrated that inclusion of hydroxylamine prevented further metabolism of cysteinesulfinic acid. which occurred rapidly in the absence of hydroxylamine

  15. Knockout of the murine cysteine dioxygenase gene results in severe impairment in ability to synthesize taurine and an increased catabolism of cysteine to hydrogen sulfide

    Science.gov (United States)

    Ueki, Iori; Roman, Heather B.; Valli, Alessandro; Fieselmann, Krista; Lam, Jimmy; Peters, Rachel; Hirschberger, Lawrence L.

    2011-01-01

    Cysteine homeostasis is dependent on the regulation of cysteine dioxygenase (CDO) in response to changes in sulfur amino acid intake. CDO oxidizes cysteine to cysteinesulfinate, which is further metabolized to either taurine or to pyruvate plus sulfate. To gain insight into the physiological function of CDO and the consequence of a loss of CDO activity, mice carrying a null CDO allele (CDO+/− mice) were crossed to generate CDO−/−, CDO+/−, and CDO+/+ mice. CDO−/− mice exhibited postnatal mortality, growth deficit, and connective tissue pathology. CDO−/− mice had extremely low taurine levels and somewhat elevated cysteine levels, consistent with the lack of flux through CDO-dependent catabolic pathways. However, plasma sulfate levels were slightly higher in CDO−/− mice than in CDO+/− or CDO+/+ mice, and tissue levels of acid-labile sulfide were elevated, indicating an increase in cysteine catabolism by cysteine desulfhydration pathways. Null mice had lower hepatic cytochrome c oxidase levels, suggesting impaired electron transport capacity. Supplementation of mice with taurine improved survival of male pups but otherwise had little effect on the phenotype of the CDO−/− mice. H2S has been identified as an important gaseous signaling molecule as well as a toxicant, and pathology may be due to dysregulation of H2S production. Control of cysteine levels by regulation of CDO may be necessary to maintain low H2S/sulfane sulfur levels and facilitate the use of H2S as a signaling molecule. PMID:21693692

  16. [Knockdown of indoleamine 2, 3-dioxygenase 2 (IDO2)gene inhibits tumor growth and enhances immune function in mice bearing melanoma].

    Science.gov (United States)

    Liu, Yanling; Liu, Huan; Xiang, Yingqing; Chen, Xiaoyan; Xu, Ping; Min, Weiping

    2017-12-01

    Objective To study the role of indoleamine 2, 3-dioxygenase 2 (IDO2) in anti-tumor therapy and its effect on the immune response when using IDO2 as therapeutic target. Methods B16-BL6 cells were used to construct mouse xenografted melanoma model. IDO2-shRNA that contained IDO2-siRNA or control shRNA (scrambled-shRNA) was injected hydrodynamically via the tail vein to treat melanoma. The tumor size was measured by vernier caliper. Flow cytometry was performed to analyze the percentage of regulatory T cells (Tregs), T cell apoptosis rate in draining lymph nodes and the expressions of co-stimulatory molecules on splenic dendritic cells (DCs) from different treatment groups. The lactate dehydrogenase (LDH) assay was used to determine the CD8 + cytotoxic T lymphocyte (CTL) activity. The serum levels of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) were detected by ELISA. Results In the IDO2-shRNA treated group, the tumor formation time was delayed, tumor grew slowly, and excised tumor mass was significantly reduced. IDO2-shRNA treatment also decreased the percentage of Tregs and T cell apoptosis in draining lymph nodes and increased the expressions of co-stimulatory molecules CD80 and CD86 on splenic DCs. The capacity of CD8 + T cells to kill B16-BL6 cells was enhanced and the serum levels of TNF-α and IFN-γ were upregulated. Conclusion Silencing IDO2 can effectively inhibit the growth of melanoma and improve the anti-tumor immune response in vivo.

  17. Unraveling the estrogen receptor (er) genes in Atlantic salmon (Salmo salar) reveals expression differences between the two adult life stages but little impact from polychlorinated biphenyl (PCB) load.

    Science.gov (United States)

    Nikoleris, Lina; Hansson, Maria C

    2015-01-15

    Estrogen receptors (ers) not only are activated by hormones but also interact with many human-derived environmental contaminants. Here, we present evidence for four expressed er genes in Atlantic salmon cDNA - two more ers (erα2 and erβ2) than previously published. To determine if er gene expression differs between two adult life-stages we sampled 20 adult salmon from the feeding phase in the Baltic Sea and during migration in the River Mörrum, Sweden. Results show that all four er genes are present in the investigated tissues, except for erα2 not appearing in the spleen. Overall, a profile analysis reveals the erα1 gene to be the most highly expressed er gene in both female and male Baltic Sea salmon tissues, and also in female River Mörrum salmon. In contrast, this gene has the lowest gene expression level of the four er genes in male salmon from the River Mörrum. The erα2 gene is expressed at the lowest levels in both female/male Baltic Sea salmon and in female River Mörrum salmon. Statistical analyses indicate a significant and complex interaction where both sex and adult life stage can impact er gene expression. Regression analyses did not demonstrate any significant relationship between polychlorinated biphenyl (PCB) body burden and er gene expression level, suggesting that accumulated pollutants from the Baltic Sea may be deactivated inside the salmon's lipid tissues and have limited impact on er activity. This study is the first comprehensive analysis of four er gene expression levels in two wild salmon populations from two different adult life stages where information about PCB load is also available. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Phytoalexins of the Pyrinae: Biphenyls and dibenzofurans

    Directory of Open Access Journals (Sweden)

    Cornelia Chizzali

    2012-04-01

    Full Text Available Biphenyls and dibenzofurans are the phytoalexins of the Pyrinae, a subtribe of the plant family Rosaceae. The Pyrinae correspond to the long-recognized Maloideae. Economically valuable species of the Pyrinae are apples and pears. Biphenyls and dibenzofurans are formed de novo in response to infection by bacterial and fungal pathogens. The inducible defense compounds were also produced in cell suspension cultures after treatment with biotic and abiotic elicitors. The antimicrobial activity of the phytoalexins was demonstrated. To date, 10 biphenyls and 17 dibenzofurans were isolated from 14 of the 30 Pyrinae genera. The most widely distributed compounds are the biphenyl aucuparin and the dibenzofuran γ-cotonefuran. The biosynthesis of the two classes of defense compounds is not well understood, despite the importance of the fruit crops. More recent studies have revealed simultaneous accumulation of biphenyls and dibenzofurans, suggesting sequential, rather than the previously proposed parallel, biosynthetic pathways. Elicitor-treated cell cultures of Sorbus aucuparia served as a model system for studying phytoalexin metabolism. The key enzyme that forms the carbon skeleton is biphenyl synthase. The starter substrate for this type-III polyketide synthase is benzoyl-CoA. In apples, biphenyl synthase is encoded by a gene family, members of which are differentially regulated. Metabolism of the phytoalexins may provide new tools for designing disease control strategies for fruit trees of the Pyrinae subtribe.

  19. Hydrogen Peroxide-induced Cell Death in Arabidopsis : Transcriptional and Mutant Analysis Reveals a Role of an Oxoglutarate-dependent Dioxygenase Gene in the Cell Death Process

    NARCIS (Netherlands)

    Gechev, Tsanko S.; Minkov, Ivan N.; Hille, Jacques

    2005-01-01

    Hydrogen peroxide is a major regulator of plant programmed cell death (PCD) but little is known about the downstream genes from the H2O2-signaling network that mediate the cell death. To address this question, a novel system for studying H2O2-induced programmed cell death in Arabidopsis thaliana was

  20. Overexpression of a 9-cis-Epoxycarotenoid Dioxygenase Gene in Nicotiana plumbaginifolia Increases Abscisic Acid and Phaseic Acid Levels and Enhances Drought Tolerance1

    Science.gov (United States)

    Qin, Xiaoqiong; Zeevaart, Jan A.D.

    2002-01-01

    The plant hormone abscisic acid (ABA) plays important roles in seed maturation and dormancy and in adaptation to a variety of environmental stresses. An effort to engineer plants with elevated ABA levels and subsequent stress tolerance is focused on the genetic manipulation of the cleavage reaction. It has been shown in bean (Phaseolus vulgaris) that the gene encoding the cleavage enzyme (PvNCED1) is up-regulated by water stress, preceding accumulation of ABA. Transgenic wild tobacco (Nicotiana plumbaginifolia Viv.) plants were produced that overexpress the PvNCED1 gene either constitutively or in an inducible manner. The constitutive expression of PvNCED1 resulted in an increase in ABA and its catabolite, phaseic acid (PA). When the PvNCED1 gene was driven by the dexamethasone (DEX)-inducible promoter, a transient induction of PvNCED1 message and accumulation of ABA and PA were observed in different lines after application of DEX. Accumulation of ABA started to level off after 6 h, whereas the PA level continued to increase. In the presence of DEX, seeds from homozygous transgenic line TN1 showed a 4-d delay in germination. After spraying with DEX, the detached leaves from line TN1 had a drastic decrease in their water loss relative to control leaves. These plants also showed a marked increase in their tolerance to drought stress. These results indicate that it is possible to manipulate ABA levels in plants by overexpressing the key regulatory gene in ABA biosynthesis and that stress tolerance can be improved by increasing ABA levels. PMID:11842158

  1. Overexpression of a 9-cis-epoxycarotenoid dioxygenase gene in Nicotiana plumbaginifolia increases abscisic acid and phaseic acid levels and enhances drought tolerance.

    Science.gov (United States)

    Qin, Xiaoqiong; Zeevaart, Jan A D

    2002-02-01

    The plant hormone abscisic acid (ABA) plays important roles in seed maturation and dormancy and in adaptation to a variety of environmental stresses. An effort to engineer plants with elevated ABA levels and subsequent stress tolerance is focused on the genetic manipulation of the cleavage reaction. It has been shown in bean (Phaseolus vulgaris) that the gene encoding the cleavage enzyme (PvNCED1) is up-regulated by water stress, preceding accumulation of ABA. Transgenic wild tobacco (Nicotiana plumbaginifolia Viv.) plants were produced that overexpress the PvNCED1 gene either constitutively or in an inducible manner. The constitutive expression of PvNCED1 resulted in an increase in ABA and its catabolite, phaseic acid (PA). When the PvNCED1 gene was driven by the dexamethasone (DEX)-inducible promoter, a transient induction of PvNCED1 message and accumulation of ABA and PA were observed in different lines after application of DEX. Accumulation of ABA started to level off after 6 h, whereas the PA level continued to increase. In the presence of DEX, seeds from homozygous transgenic line TN1 showed a 4-d delay in germination. After spraying with DEX, the detached leaves from line TN1 had a drastic decrease in their water loss relative to control leaves. These plants also showed a marked increase in their tolerance to drought stress. These results indicate that it is possible to manipulate ABA levels in plants by overexpressing the key regulatory gene in ABA biosynthesis and that stress tolerance can be improved by increasing ABA levels.

  2. Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes.

    Science.gov (United States)

    Dunaway, Keith W; Islam, M Saharul; Coulson, Rochelle L; Lopez, S Jesse; Vogel Ciernia, Annie; Chu, Roy G; Yasui, Dag H; Pessah, Isaac N; Lott, Paul; Mordaunt, Charles; Meguro-Horike, Makiko; Horike, Shin-Ichi; Korf, Ian; LaSalle, Janine M

    2016-12-13

    Rare variants enriched for functions in chromatin regulation and neuronal synapses have been linked to autism. How chromatin and DNA methylation interact with environmental exposures at synaptic genes in autism etiologies is currently unclear. Using whole-genome bisulfite sequencing in brain tissue and a neuronal cell culture model carrying a 15q11.2-q13.3 maternal duplication, we find that significant global DNA hypomethylation is enriched over autism candidate genes and affects gene expression. The cumulative effect of multiple chromosomal duplications and exposure to the pervasive persistent organic pollutant PCB 95 altered methylation of more than 1,000 genes. Hypomethylated genes were enriched for H2A.Z, increased maternal UBE3A in Dup15q corresponded to reduced levels of RING1B, and bivalently modified H2A.Z was altered by PCB 95 and duplication. These results demonstrate the compounding effects of genetic and environmental insults on the neuronal methylome that converge upon dysregulation of chromatin and synaptic genes. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. A luciferase reporter gene assay and aryl hydrocarbon receptor 1 genotype predict the LD50 of polychlorinated biphenyls in avian species

    International Nuclear Information System (INIS)

    Manning, Gillian E.; Farmahin, Reza; Crump, Doug; Jones, Stephanie P.; Klein, Jeff; Konstantinov, Alex; Potter, Dave; Kennedy, Sean W.

    2012-01-01

    Birds differ in sensitivity to the embryotoxic effects of polychlorinated biphenyls (PCBs), which complicates environmental risk assessments for these chemicals. Recent research has shown that the identities of amino acid residues 324 and 380 in the avian aryl hydrocarbon receptor 1 (AHR1) ligand binding domain (LBD) are primarily responsible for differences in avian species sensitivity to selected dibenzo-p-dioxins and furans. A luciferase reporter gene (LRG) assay was developed in our laboratory to measure AHR1-mediated induction of a cytochrome P450 1A5 reporter gene in COS-7 cells transfected with different avian AHR1 constructs. In the present study, the LRG assay was used to measure the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and PCBs 126, 77, 105 and 118 on luciferase activity in COS-7 cells transfected with AHR1 constructs representative of 86 avian species in order to predict their sensitivity to PCB-induced embryolethality and the relative potency of PCBs in these species. The results of the LRG assay indicate that the identity of amino acid residues 324 and 380 in the AHR1 LBD are the major determinants of avian species sensitivity to PCBs. The relative potency of PCBs did not differ greatly among AHR1 constructs. Luciferase activity was significantly correlated with embryolethality data obtained from the literature (R 2 ≥ 0.87, p < 0.0001). Thus, the LRG assay in combination with the knowledge of a species' AHR1 LBD sequence can be used to predict PCB-induced embryolethality in potentially any avian species of interest without the use of lethal methods on a large number of individuals. -- Highlights: ► PCB embryolethality in birds can be predicted from a species' AHR1 genotype. ► The reporter gene assay is useful for predicting species sensitivity to PCBs. ► The relative potency of PCBs does not appear to differ between AHR1 genotypes. ► Contamination of PCB 105 and PCB 118 did not affect their relative

  4. A luciferase reporter gene assay and aryl hydrocarbon receptor 1 genotype predict the LD{sub 50} of polychlorinated biphenyls in avian species

    Energy Technology Data Exchange (ETDEWEB)

    Manning, Gillian E., E-mail: gmann017@uottawa.ca [Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 (Canada); Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Farmahin, Reza, E-mail: mfarm070@uottawa.ca [Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 (Canada); Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Crump, Doug, E-mail: doug.crump@ec.gc.ca [Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Jones, Stephanie P., E-mail: stephanie.jones@ec.gc.ca [Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Klein, Jeff, E-mail: jeffery@well-labs.com [Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3M5 (Canada); Konstantinov, Alex, E-mail: alex@well-labs.com [Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3M5 (Canada); Potter, Dave, E-mail: dpotter@well-labs.com [Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3M5 (Canada); Kennedy, Sean W., E-mail: sean.kennedy@ec.gc.ca [Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 (Canada); Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada)

    2012-09-15

    Birds differ in sensitivity to the embryotoxic effects of polychlorinated biphenyls (PCBs), which complicates environmental risk assessments for these chemicals. Recent research has shown that the identities of amino acid residues 324 and 380 in the avian aryl hydrocarbon receptor 1 (AHR1) ligand binding domain (LBD) are primarily responsible for differences in avian species sensitivity to selected dibenzo-p-dioxins and furans. A luciferase reporter gene (LRG) assay was developed in our laboratory to measure AHR1-mediated induction of a cytochrome P450 1A5 reporter gene in COS-7 cells transfected with different avian AHR1 constructs. In the present study, the LRG assay was used to measure the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and PCBs 126, 77, 105 and 118 on luciferase activity in COS-7 cells transfected with AHR1 constructs representative of 86 avian species in order to predict their sensitivity to PCB-induced embryolethality and the relative potency of PCBs in these species. The results of the LRG assay indicate that the identity of amino acid residues 324 and 380 in the AHR1 LBD are the major determinants of avian species sensitivity to PCBs. The relative potency of PCBs did not differ greatly among AHR1 constructs. Luciferase activity was significantly correlated with embryolethality data obtained from the literature (R{sup 2} ≥ 0.87, p < 0.0001). Thus, the LRG assay in combination with the knowledge of a species' AHR1 LBD sequence can be used to predict PCB-induced embryolethality in potentially any avian species of interest without the use of lethal methods on a large number of individuals. -- Highlights: ► PCB embryolethality in birds can be predicted from a species' AHR1 genotype. ► The reporter gene assay is useful for predicting species sensitivity to PCBs. ► The relative potency of PCBs does not appear to differ between AHR1 genotypes. ► Contamination of PCB 105 and PCB 118 did not affect

  5. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Manning, Gillian E., E-mail: gmann017@uottawa.ca [Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 (Canada); Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Mundy, Lukas J., E-mail: lukas.mundy@ec.gc.ca [Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 (Canada); Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Crump, Doug, E-mail: doug.crump@ec.gc.ca [Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Jones, Stephanie P., E-mail: stephanie.jones@ec.gc.ca [Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Chiu, Suzanne, E-mail: suzanne.chiu@ec.gc.ca [Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada); Klein, Jeff, E-mail: jeffery@well-labs.com [Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3chsM5 (Canada); Konstantinov, Alex, E-mail: alex@well-labs.com [Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3chsM5 (Canada); Potter, Dave, E-mail: dpotter@well-labs.com [Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3chsM5 (Canada); Kennedy, Sean W., E-mail: sean.kennedy@ec.gc.ca [Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 (Canada); Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada)

    2013-01-01

    Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of

  6. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity

    International Nuclear Information System (INIS)

    Manning, Gillian E.; Mundy, Lukas J.; Crump, Doug; Jones, Stephanie P.; Chiu, Suzanne; Klein, Jeff; Konstantinov, Alex; Potter, Dave; Kennedy, Sean W.

    2013-01-01

    Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of toxicity than CYP

  7. Molecular Characterization of the Genes pcaG and pcaH, Encoding Protocatechuate 3,4-Dioxygenase, Which Are Essential for Vanillin Catabolism in Pseudomonas sp. Strain HR199

    Science.gov (United States)

    Overhage, Jörg; Kresse, Andreas U.; Priefert, Horst; Sommer, Horst; Krammer, Gerhard; Rabenhorst, Jürgen; Steinbüchel, Alexander

    1999-01-01

    Pseudomonas sp. strain HR199 is able to utilize eugenol (4-allyl-2-methoxyphenol), vanillin (4-hydroxy-3-methoxybenzaldehyde), or protocatechuate as the sole carbon source for growth. Mutants of this strain which were impaired in the catabolism of vanillin but retained the ability to utilize eugenol or protocatechuate were obtained after nitrosoguanidine mutagenesis. One mutant (SK6169) was used as recipient of a Pseudomonas sp. strain HR199 genomic library in cosmid pVK100, and phenotypic complementation was achieved with a 5.8-kbp EcoRI fragment (E58). The amino acid sequences deduced from two corresponding open reading frames (ORF) identified on E58 revealed high degrees of homology to pcaG and pcaH, encoding the two subunits of protocatechuate 3,4-dioxygenase. Three additional ORF most probably encoded a 4-hydroxybenzoate 3-hydroxylase (PobA) and two putative regulatory proteins, which exhibited homology to PcaQ of Agrobacterium tumefaciens and PobR of Pseudomonas aeruginosa, respectively. Since mutant SK6169 was also complemented by a subfragment of E58 that harbored only pcaH, this mutant was most probably lacking a functional β subunit of the protocatechuate 3,4-dioxygenase. Since this mutant was still able to grow on protocatechuate and lacked protocatechuate 4,5-dioxygenase and protocatechuate 2,3-dioxygenase, the degradation had to be catalyzed by different enzymes. Two other mutants (SK6184 and SK6190), which were also impaired in the catabolism of vanillin, were not complemented by fragment E58. Since these mutants accumulated 3-carboxy muconolactone during cultivation on eugenol, they most probably exhibited a defect in a step of the catabolic pathway following the ortho cleavage. Moreover, in these mutants cyclization of 3-carboxymuconic acid seems to occur by a syn absolute stereochemical course, which is normally only observed for cis,cis-muconate lactonization in pseudomonads. In conclusion, vanillin is degraded through the ortho-cleavage pathway

  8. Induction of 9-cis-epoxycarotenoid dioxygenase in Arabidopsis thaliana seeds enhances seed dormancy

    OpenAIRE

    Martínez-Andújar, Cristina; Ordiz, M. Isabel; Huang, Zhonglian; Nonogaki, Mariko; Beachy, Roger N.; Nonogaki, Hiroyuki

    2011-01-01

    Full understanding of mechanisms that control seed dormancy and germination remains elusive. Whereas it has been proposed that translational control plays a predominant role in germination, other studies suggest the importance of specific gene expression patterns in imbibed seeds. Transgenic plants were developed to permit conditional expression of a gene encoding 9-cis-epoxycarotenoid dioxygenase 6 (NCED6), a rate-limiting enzyme in abscisic acid (ABA) biosynthesis, using the ecdysone recept...

  9. Indoleamine 2,3-dioxygenase vaccination

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Svane, Inge Marie

    2015-01-01

    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. Remarkably, we discovered IDO-specific T cells that can influence adaptive immune reactions in patients with cancer. Further, a recent phase I clinical trial demonstrated long-lasting disease stabilization without toxicity in patien...... with non-small-cell lung cancer (NSCLC) who were vaccinated with an IDO-derived HLA-A2-restricted epitope....

  10. Regiospecific and stereoselective hydroxylation of 1-indanone and 2-indanone by naphthalene dioxygenase and toluene dioxygenase.

    OpenAIRE

    Resnick, S M; Torok, D S; Lee, K; Brand, J M; Gibson, D T

    1994-01-01

    The biotransformation of 1-indanone and 2-indanone to hydroxyindanones was examined with bacterial strains expressing naphthalene dioxygenase (NDO) and toluene dioxygenase (TDO) as well as with purified enzyme components. Pseudomonas sp. strain 9816/11 cells, expressing NDO, oxidized 1-indanone to a mixture of 3-hydroxy-1-indanone (91%) and 2-hydroxy-1-indanone (9%). The (R)-3-hydroxy-1-indanone was formed in 62% enantiomeric excess (ee) (R:S, 81:19), while the 2-hydroxy-1-indanone was racemi...

  11. The metabolism of biphenyl

    International Nuclear Information System (INIS)

    Meyer, T.; Aarbakke, J.; Scheline, R.R.

    1976-01-01

    The metabolic disposition of 14 C-biphenyl in the rat was studied by liquid scintillation counting. The rats were given an oral dose of 14 C-biphenyl (100 mg/kg, 0.7-1.0 μci) and the total excretion of radioactivity after 96 hrs was 92.2% of the dose. Urinary excretion accounted for 84.8% and faecal excretion for 7.3% of the dose. Most of this radioactivity, 75.8% and 5.8% respectively, was excreted within 24 hrs. Only trace amounts of 14 CO 2 were detected in the expired air and 0.6% of the dose was found to be still present in the rats 96 hrs after biphenyl administration. Extraction and fractionation of the 24 hrs urine samples showed that the largest fraction (nearly 30% of the dose) consisted of conjugated phenolic metabolites. Acidic metabolites accounted for a quarter of the dose and the low levels of expired 14 CO 2 indicated that these were not products resulting from extensive degradation and decarboxylation. (author)

  12. Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells.

    Science.gov (United States)

    Curti, Antonio; Trabanelli, Sara; Onofri, Chiara; Aluigi, Michela; Salvestrini, Valentina; Ocadlikova, Darina; Evangelisti, Cecilia; Rutella, Sergio; De Cristofaro, Raimondo; Ottaviani, Emanuela; Baccarani, Michele; Lemoli, Roberto M

    2010-12-01

    The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia. Leukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels. We demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan. Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3-dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they inhibit naive T-cell proliferation and impair the complete maturation of normal dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells are capable of in vitro suppression of a leukemia-specific T cell-mediated immune response, directed against the leukemia-associated antigen, Wilms' tumor protein. These data identify

  13. Characterization of dioxygenases and biosurfactants produced by crude oil degrading soil bacteria

    Directory of Open Access Journals (Sweden)

    Santhakumar Muthukamalam

    Full Text Available ABSTRACT Role of microbes in bioremediation of oil spills has become inevitable owing to their eco friendly nature. This study focused on the isolation and characterization of bacterial strains with superior oil degrading potential from crude-oil contaminated soil. Three such bacterial strains were selected and subsequently identified by 16S rRNA gene sequence analysis as Corynebacterium aurimucosum, Acinetobacter baumannii and Microbacterium hydrocarbonoxydans respectively. The specific activity of catechol 1,2 dioxygenase (C12O and catechol 2,3 dioxygenase (C23O was determined in these three strains wherein the activity of C12O was more than that of C23O. Among the three strains, Microbacterium hydrocarbonoxydans exhibited superior crude oil degrading ability as evidenced by its superior growth rate in crude oil enriched medium and enhanced activity of dioxygenases. Also degradation of total petroleum hydrocarbon (TPH in crude oil was higher with Microbacterium hydrocarbonoxydans. The three strains also produced biosurfactants of glycolipid nature as indicated d by biochemical, FTIR and GCMS analysis. These findings emphasize that such bacterial strains with superior oil degrading capacity may find their potential application in bioremediation of oil spills and conservation of marine and soil ecosystem.

  14. Molecular evolution of flavonoid dioxygenases in the family Apiaceae.

    Science.gov (United States)

    Gebhardt, Yvonne; Witte, Simone; Forkmann, Gert; Lukacin, Richard; Matern, Ulrich; Martens, Stefan

    2005-06-01

    Plant species of the family Apiaceae are known to accumulate flavonoids mainly in the form of flavones and flavonols. Three 2-oxoglutarate-dependent dioxygenases, flavone synthase or flavanone 3 beta-hydroxylase and flavonol synthase are involved in the biosynthesis of these secondary metabolites. The corresponding genes were cloned recently from parsley (Petroselinum crispum) leaves. Flavone synthase I appears to be confined to the Apiaceae, and the unique occurrence as well as its high sequence similarity to flavanone 3beta-hydroxylase laid the basis for evolutionary studies. In order to examine the relationship of these two enzymes throughout the Apiaceae, RT-PCR based cloning and functional identification of flavone synthases I or flavanone 3beta-hydroxylases were accomplished from Ammi majus, Anethum graveolens, Apium graveolens, Pimpinella anisum, Conium maculatum and Daucus carota, yielding three additional synthase and three additional hydroxylase cDNAs. Molecular and phylogenetic analyses of these sequences were compatible with the phylogeny based on morphological characteristics and suggested that flavone synthase I most likely resulted from gene duplication of flavanone 3beta-hydroxylase, and functional diversification at some point during the development of the apiaceae subfamilies. Furthermore, the genomic sequences from Petroselinum crispum and Daucus carota revealed two introns in each of the synthases and a lack of introns in the hydroxylases. These results might be explained by intron losses from the hydroxylases occurring at a later stage of evolution.

  15. Differential Expression of Cysteine Dioxygenase 1 in Complex Karyotype Liposarcomas

    Directory of Open Access Journals (Sweden)

    Mohammed Shaker

    2014-01-01

    Full Text Available Altered cysteine dioxygenase 1 (CDO1 gene expression has been observed in several cancers but has not yet been investigated in liposarcomas. The aim of this study was to evaluate CDO1 expression in a cohort of liposarcomas and to determine its association with clinicopathological features. Existing microarray data indicated variable CDO1 expression in liposarcoma subtypes. CDO1 mRNA from a larger cohort of liposarcomas was quantified by real time-PCR, and CDO1 protein expression was determined by immunohistochemistry (IHC in more than 300 tumor specimens. Well-differentiated liposarcomas (WDLSs had significantly higher CDO1 gene expression and protein levels than dedifferentiated liposarcomas (DDLSs ( P < 0.001. Location of the tumor was not predictive of the expression level of CDO1 mRNA in any histological subtype of liposarcoma. Recurrent tumors did not show any difference in CDO1 expression when compared to primary tumors. CDO1 expression was upregulated as human mesenchymal stem cells (hMSCs undergo differentiation into mature adipocytes. Our results suggest that CDO1 is a marker of liposarcoma progression and adipogenic differentiation.

  16. Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

    International Nuclear Information System (INIS)

    Al-Salman, Fadheela; Plant, Nick

    2012-01-01

    The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation of PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ► Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ► PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ► Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ► Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ► PCB153 is the most potent activator of PXR/CAR target gene in all tissues.

  17. Characterization and Functional Identification of a Novel Plant 4,5-Extradiol Dioxygenase Involved in Betalain Pigment Biosynthesis in Portulaca grandiflora

    Science.gov (United States)

    Christinet, Laurent; Burdet, Frédéric X.; Zaiko, Maïa; Hinz, Ursula; Zrÿd, Jean-Pierre

    2004-01-01

    Betalains are pigments that replace anthocyanins in the majority of families of the plant order Caryophyllales. Betalamic acid is the common chromophore of betalains. The key enzyme of the betalain biosynthetic pathway is an extradiol dioxygenase that opens the cyclic ring of dihydroxy-phenylalanine (DOPA) between carbons 4 and 5, thus producing an unstable seco-DOPA that rearranges nonenzymatically to betalamic acid. A gene for a 4,5-DOPA-dioxygenase has already been isolated from the fungus Amanita muscaria, but no homolog was ever found in plants. To identify the plant gene, we constructed subtractive libraries between different colored phenotypes of isogenic lines of Portulaca grandiflora (Portulacaceae) and between different stages of flower bud formation. Using in silico analysis of differentially expressed cDNAs, we identified a candidate showing strong homology at the level of translated protein with the LigB domain present in several bacterial extradiol 4,5-dioxygenases. The gene was expressed only in colored flower petals. The function of this gene in the betalain biosynthetic pathway was confirmed by biolistic genetic complementation in white petals of P. grandiflora genotypes lacking the gene for color formation. This gene named DODA is the first characterized member of a novel family of plant dioxygenases phylogenetically distinct from Amanita sp. DOPA-dioxygenase. Homologs of DODA are present not only in betalain-producing plants but also, albeit with some changes near the catalytic site, in other angiosperms and in the bryophyte Physcomitrella patens. These homologs are part of a novel conserved plant gene family probably involved in aromatic compound metabolism. PMID:14730069

  18. Characterization of transgenic tobacco plants containing bacterial bphC gene and study of their phytoremediation ability.

    Science.gov (United States)

    Viktorovtá, Jitka; Novakova, Martina; Trbolova, Ladislava; Vrchotova, Blanka; Lovecka, Petra; Mackova, Martina; Macek, Tomas

    2014-01-01

    Genetically modified plants can serve as an efficient tool for remediation of diverse dangerous pollutants of the environment such as pesticides, heavy metals, explosives and persistent organic compounds. Transgenic lines of Nicotiana tabacum containing bacterial bphC gene from the degradation pathway of polychlorinated biphenyls (PCBs) were tested. The product of the bphC gene - enzyme 2,3-dihydroxybiphenyl-1,2-dioxygenase is responsible for cleaving of the biphenyl ring. The presence of bphC gene in transgenic plants was detected on DNA, RNA and protein level. The expression of the bphC/His gene was verified afterpurification of the enzyme from plants by affinity chromatography followed by a Western blot and immunochemical assay. The enzyme activity of isolated protein was detected. Efficient transformation of 2,3-DHB by transgenic plants was achieved and the lines also exhibited high production of biomass. The transgenic plants were more tolerant to the commercial PCBs mixture Delor 103 than non-transgenic tobacco. And finally, the higher decrease of total PCB content and especially congener 28 in real contaminated soil from a dumpsite was determined after cultivation of transgenic plant in comparison with nontransgenic tobacco. The substrate specificity of transgenic plants was the same as substrate specificity of BphC enzyme.

  19. Regiospecific and stereoselective hydroxylation of 1-indanone and 2-indanone by naphthalene dioxygenase and toluene dioxygenase.

    Science.gov (United States)

    Resnick, S M; Torok, D S; Lee, K; Brand, J M; Gibson, D T

    1994-09-01

    The biotransformation of 1-indanone and 2-indanone to hydroxyindanones was examined with bacterial strains expressing naphthalene dioxygenase (NDO) and toluene dioxygenase (TDO) as well as with purified enzyme components. Pseudomonas sp. strain 9816/11 cells, expressing NDO, oxidized 1-indanone to a mixture of 3-hydroxy-1-indanone (91%) and 2-hydroxy-1-indanone (9%). The (R)-3-hydroxy-1-indanone was formed in 62% enantiomeric excess (ee) (R:S, 81:19), while the 2-hydroxy-1-indanone was racemic. The same cells also formed 2-hydroxy-1-indanone from 2-indanone. Purified NDO components oxidized 1-indanone and 2-indanone to the same products produced by strain 9816/11. P. putida F39/D cells, expressing TDO, oxidized 2-indanone to (S)-2-hydroxy-1-indanone of 76% ee (R:S, 12:88) but did not oxidize 1-indanone efficiently. Purified TDO components also oxidized 2-indanone to (S)-2-hydroxy-1-indanone of 90% ee (R:S, 5:95) and failed to oxidize 1-indanone. Oxidation of 1- and 2-indanone in the presence of [18O]oxygen indicated that the hydroxyindanones were formed by the incorporation of a single atom of molecular oxygen (monooxygenation) rather than by the dioxygenation of enol tautomers of the ketone substrates. As alternatives to chemical synthesis, these biotransformations represent direct routes to 3-hydroxy-1-indanone and 2-hydroxy-1-indanone as the major products from 1-indanone and 2-indanone, respectively.

  20. Exploring the mechanism of tryptophan 2,3-dioxygenase

    Science.gov (United States)

    Thackray, Sarah J.; Mowat, Christopher G.; Chapman, Stephen K.

    2008-01-01

    The haem proteins TDO (tryptophan 2,3-dioxygenase) and IDO (indoleamine 2,3-dioxygenase) are specific and powerful oxidation catalysts that insert one molecule of dioxygen into L-tryptophan in the first and rate-limiting step in the kynurenine pathway. Recent crystallographic and biochemical analyses of TDO and IDO have greatly aided our understanding of the mechanisms employed by these enzymes in the binding and activation of dioxygen and tryptophan. In the present paper, we briefly discuss the function, structure and possible catalytic mechanism of these enzymes. PMID:19021508

  1. Thermic decomposition of biphenyl; Decomposition thermique du biphenyle

    Energy Technology Data Exchange (ETDEWEB)

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

    1966-03-01

    Liquid and vapour phase pyrolysis of very pure biphenyl obtained by methods described in the text was carried out at 400 C in sealed ampoules, the fraction transformed being always less than 0.1 per cent. The main products were hydrogen, benzene, terphenyls, and a deposit of polyphenyls strongly adhering to the walls. Small quantities of the lower aliphatic hydrocarbons were also found. The variation of the yields of these products with a) the pyrolysis time, b) the state (gas or liquid) of the biphenyl, and c) the pressure of the vapour was measured. Varying the area and nature of the walls showed that in the absence of a liquid phase, the pyrolytic decomposition takes place in the adsorbed layer, and that metallic walls promote the reaction more actively than do those of glass (pyrex or silica). A mechanism is proposed to explain the results pertaining to this decomposition in the adsorbed phase. The adsorption seems to obey a Langmuir isotherm, and the chemical act which determines the overall rate of decomposition is unimolecular. (author) [French] Du biphenyle tres pur, dont la purification est decrite, est pyrolyse a 400 C en phase vapeur et en phase liquide dans des ampoules scellees sous vide, a des taux de decomposition n'ayant jamais depasse 0,1 pour cent. Les produits provenant de la pyrolyse sont essentiellement: l' hydrogene, le benzene, les therphenyles, et un depot de polyphenyles adherant fortement aux parois. En plus il se forme de faibles quantites d'hydrocarbures aliphatiques gazeux. On indique la variation des rendements des differents produits avec la duree de pyrolyse, l'etat gazeux ou liquide du biphenyle, et la pression de la vapeur. Variant la superficie et la nature des parois, on montre qu'en absence de liquide la pyrolyse se fait en phase adsorbee. La pyrolyse est plus active au contact de parois metalliques que de celles de verres (pyrex ou silice). A partir des resultats experimentaux un mecanisme de degradation du biphenyle en phase

  2. Thermal decomposition of biphenyl (1963); Decomposition thermique du biphenyle (1963)

    Energy Technology Data Exchange (ETDEWEB)

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

    1962-06-15

    The rates of formation of the decomposition products of biphenyl; hydrogen, methane, ethane, ethylene, as well as triphenyl have been measured in the vapour and liquid phases at 460 deg. C. The study of the decomposition products of biphenyl at different temperatures between 400 and 460 deg. C has provided values of the activation energies of the reactions yielding the main products of pyrolysis in the vapour phase. Product and Activation energy: Hydrogen 73 {+-} 2 kCal/Mole; Benzene 76 {+-} 2 kCal/Mole; Meta-triphenyl 53 {+-} 2 kCal/Mole; Biphenyl decomposition 64 {+-} 2 kCal/Mole; The rate of disappearance of biphenyl is only very approximately first order. These results show the major role played at the start of the decomposition by organic impurities which are not detectable by conventional physico-chemical analysis methods and the presence of which accelerates noticeably the decomposition rate. It was possible to eliminate these impurities by zone-melting carried out until the initial gradient of the formation curves for the products became constant. The composition of the high-molecular weight products (over 250) was deduced from the mean molecular weight and the dosage of the aromatic C - H bonds by infrared spectrophotometry. As a result the existence in tars of hydrogenated tetra, penta and hexaphenyl has been demonstrated. (author) [French] Les vitesses de formation des produits de decomposition du biphenyle: hydrogene, methane, ethane, ethylene, ainsi que des triphenyles, ont ete mesurees en phase vapeur et en phase liquide a 460 deg. C. L'etude des produits de decomposition du biphenyle a differentes temperatures comprises entre 400 et 460 deg. C, a fourni les valeurs des energies d'activation des reactions conduisant aux principaux produits de la pyrolyse en phase vapeur. Produit et Energie d'activation: Hydrogene 73 {+-} 2 kcal/Mole; Benzene 76 {+-} 2 kcal/Mole; Metatriphenyle, 53 {+-} 2 kcal/Mole; Decomposition du biphenyle 64 {+-} 2 kcal/Mole; La

  3. Isolation of recombinant cysteine dioxygenase protein from Trichophyton mentagrophytes

    Czech Academy of Sciences Publication Activity Database

    Kašperová, A.; Kunert, J.; Horynová, M.; Weigl, E.; Sebela, M.; Lenobel, René; Raška, M.

    2011-01-01

    Roč. 54, č. 5 (2011), E456-E462 ISSN 0933-7407 R&D Projects: GA ČR GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : Cysteine dioxygenase * dermatophytes * recombinant protein * keratinolytic fungi * cDNA Subject RIV: CE - Biochemistry Impact factor: 2.247, year: 2011

  4. Salix purpurea Stimulates the Expression of Specific Bacterial Xenobiotic Degradation Genes in a Soil Contaminated with Hydrocarbons.

    Directory of Open Access Journals (Sweden)

    Antoine P Pagé

    Full Text Available The objectives of this study were to uncover Salix purpurea-microbe xenobiotic degradation systems that could be harnessed in rhizoremediation, and to identify microorganisms that are likely involved in these partnerships. To do so, we tested S. purpurea's ability to stimulate the expression of 10 marker microbial oxygenase genes in a soil contaminated with hydrocarbons. In what appeared to be a detoxification rhizosphere effect, transcripts encoding for alkane 1-monooxygenases, cytochrome P450 monooxygenases, laccase/polyphenol oxidases, and biphenyl 2,3-dioxygenase small subunits were significantly more abundant in the vicinity of the plant's roots than in bulk soil. This gene expression induction is consistent with willows' known rhizoremediation capabilities, and suggests the existence of S. purpurea-microbe systems that target many organic contaminants of interest (i.e. C4-C16 alkanes, fluoranthene, anthracene, benzo(apyrene, biphenyl, polychlorinated biphenyls. An enhanced expression of the 4 genes was also observed within the bacterial orders Actinomycetales, Rhodospirillales, Burkholderiales, Alteromonadales, Solirubrobacterales, Caulobacterales, and Rhizobiales, which suggest that members of these taxa are active participants in the exposed partnerships. Although the expression of the other 6 marker genes did not appear to be stimulated by the plant at the community level, signs of additional systems that rest on their expression by members of the orders Solirubrobacterales, Sphingomonadales, Actinomycetales, and Sphingobacteriales were observed. Our study presents the first transcriptomics-based identification of microbes whose xenobiotic degradation activity in soil appears stimulated by a plant. It paints a portrait that contrasts with the current views on these consortia's composition, and opens the door for the development of laboratory test models geared towards the identification of root exudate characteristics that limit the

  5. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, Benjamin J. [Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Rojas, Itzel Y. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Murray, Iain A. [Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802 (United States); Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802 (United States); Lee, Seokwon; Hazlett, Haley F. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Perdew, Gary H. [Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802 (United States); Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802 (United States); Tomlinson, Craig R., E-mail: Craig.R.Tomlinson@Dartmouth.edu [Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States)

    2017-05-15

    Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands. Using mouse and human cell-based luciferase gene reporter assays, qPCR confirmation experiments, and CYP1A1 enzyme activity assays, we report that some of the promising clinical IDO1 inhibitors also act as agonists for the aryl hydrocarbon receptor (AHR), best known for its roles in xenobiotic metabolism and as another key regulator of the immune response. The dual role as IDO antagonist and AHR agonist for many of these IDO target drugs should be considered for full interrogation of their biological mechanisms and clinical outcomes. - Highlights: • Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors are in cancer clinical trials. • Some IDO1 inhibitors also potently activate AHR signaling. • The dual role of the IDO1 inhibitors may explain some past paradoxical findings. • AHR induction studies must be included in assessing clinical suitability.

  6. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Moyer, Benjamin J.; Rojas, Itzel Y.; Murray, Iain A.; Lee, Seokwon; Hazlett, Haley F.; Perdew, Gary H.; Tomlinson, Craig R.

    2017-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands. Using mouse and human cell-based luciferase gene reporter assays, qPCR confirmation experiments, and CYP1A1 enzyme activity assays, we report that some of the promising clinical IDO1 inhibitors also act as agonists for the aryl hydrocarbon receptor (AHR), best known for its roles in xenobiotic metabolism and as another key regulator of the immune response. The dual role as IDO antagonist and AHR agonist for many of these IDO target drugs should be considered for full interrogation of their biological mechanisms and clinical outcomes. - Highlights: • Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors are in cancer clinical trials. • Some IDO1 inhibitors also potently activate AHR signaling. • The dual role of the IDO1 inhibitors may explain some past paradoxical findings. • AHR induction studies must be included in assessing clinical suitability.

  7. THE ROLE OF 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE IN ENHANCEMENT OF SOLID-PHASE ELECTRON TRANSFER BY SHEWANELLA ONEIDENSIS MR-1

    Energy Technology Data Exchange (ETDEWEB)

    Turick, C; Amy Ekechukwu, A

    2007-06-01

    While mechanistic details of dissimilatory metal reduction are far from being understood, it is postulated that the electron transfer to solid metal oxides is mediated by outer membrane-associated c-type cytochromes and redox active electron shuttling compounds. This study focuses on the production of homogensitate in Shewanella oneidensis MR-1, an intermediate of tyrosine degradation pathway, which is a precursor of a redox cycling metabolite, pyomelanin. In this study, we determined that two enzymes involved in this pathway, 4-hydroxyphenylpyruvate dioxygenase (4HPPD) and homogentisate 1,2-dioxygenase are responsible for homogentisate production and oxidation, respectively. Inhibition of 4-HPPD activity with the specific inhibitor sulcotrione (2-(2-chloro-4-methane sulfonylbenzoyl)-1,3-cyclohexanedione), and deletion of melA, a gene encoding 4-HPPD, resulted in no pyomelanin production by S. oneidensis MR-1. Conversely, deletion of hmgA which encodes the putative homogentisate 1,2-dioxygenase, resulted in pyomelanin overproduction. The efficiency and rates, with which MR-1 reduces hydrous ferric oxide, were directly linked to the ability of mutant strains to produce pyomelanin. Electrochemical studies with whole cells demonstrated that pyomelanin substantially increases the formal potential (E{sup o}{prime}) of S. oneidensis MR-1. Based on this work, environmental production of pyomelanin likely contributes to an increased solid-phase metal reduction capacity in Shewanella oneidensis.

  8. Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: implications in alkaptonuria.

    Science.gov (United States)

    Laschi, Marcella; Tinti, Laura; Braconi, Daniela; Millucci, Lia; Ghezzi, Lorenzo; Amato, Loredana; Selvi, Enrico; Spreafico, Adriano; Bernardini, Giulia; Santucci, Annalisa

    2012-09-01

    Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. Copyright © 2011 Wiley Periodicals, Inc.

  9. Hunting down frame shifts: Ecological analysis of diverse functional gene sequences

    Directory of Open Access Journals (Sweden)

    Michal eStrejcek

    2015-11-01

    Full Text Available Functional gene ecological analyses using amplicon sequencing can be challenging as translated sequences are often burdened with shifted reading frames. The aim of this work was to evaluate several bioinformatics tools designed to correct errors which arise during sequencing in an effort to reduce the number of frame-shifts (FS. Genes encoding for alpha subunits of biphenyl (bphA and benzoate (benA dioxygenases were used as model sequences. FrameBot, a FS correction tool, was able to reduce the number of detected FS to zero. However, up to 43.1% of sequences were discarded by FrameBot as non-specific targets. Therefore, we proposed a de novo mode of FrameBot for FS correction, which works on a similar basis as common chimera identifying platforms and is not dependent on reference sequences. By nature of FrameBot de novo design, it is crucial to provide it with data as error free as possible. We tested the ability of several publicly available correction tools to decrease the number of errors in the data sets. The combination of Maximum Expected Error (MEE filtering and single linkage pre-clustering (SLP proved the most efficient read procession. Applying FrameBot de novo on the processed data enabled analysis of BphA sequences with minimal losses of potentially functional sequences not homologous to those previously known. This experiment also demonstrated the extensive diversity of dioxygenases in soil. A script which performs FrameBot de novo is presented in the supplementary material to the study and the tool was implemented into FunGene Pipeline available at http://fungene.cme.msu.edu/FunGenePipeline/ and https://github.com/rdpstaff/Framebot.

  10. Probes of the catalytic site of cysteine dioxygenase.

    Science.gov (United States)

    Chai, Sergio C; Bruyere, John R; Maroney, Michael J

    2006-06-09

    The first major step of cysteine catabolism, the oxidation of cysteine to cysteine sulfinic acid, is catalyzed by cysteine dioxygenase (CDO). In the present work, we utilize recombinant rat liver CDO and cysteine derivatives to elucidate structural parameters involved in substrate recognition and x-ray absorption spectroscopy to probe the interaction of the active site iron center with cysteine. Kinetic studies using cysteine structural analogs show that most are inhibitors and that a terminal functional group bearing a negative charge (e.g. a carboxylate) is required for binding. The substrate-binding site has no stringent restrictions with respect to the size of the amino acid. Lack of the amino or carboxyl groups at the alpha-carbon does not prevent the molecules from interacting with the active site. In fact, cysteamine is shown to be a potent activator of the enzyme without being a substrate. CDO was also rendered inactive upon complexation with the metal-binding inhibitors azide and cyanide. Unlike many non-heme iron dioxygenases that employ alpha-keto acids as cofactors, CDO was shown to be the only dioxygenase known to be inhibited by alpha-ketoglutarate.

  11. Benzylic monooxygenation catalyzed by toluene dioxygenase from Pseudomonas putida

    International Nuclear Information System (INIS)

    Wackett, L.P.; Kwart, L.D.; Gibson, D.T.

    1988-01-01

    Toluene dioxygenase, a multicomponent enzyme system known to oxidize mononuclear aromatic hydrocarbons to cis-dihydrodiols, oxidized indene and indan to 1-indenol and 1-indanol, respectively. In addition, the enzyme catalyzed dioxygen addition to the nonaromatic double bond of indene to form cis-1,2-indandiol. The oxygen atoms in 1-indenol and cis-1,2-indandiol were shown to be derived from molecular oxygen, whereas 70% of the oxygen in 1-indanol was derived from water. All of the isolated products were optically active as demonstrated by 19 F NMR and HPLC discrimination of diastereomeric esters and by chiroptic methods. The high optical purity of (-)-(1R)-indanol (84% enantiomeric excess) and the failure of scavengers of reactive oxygen species to inhibit the monooxygenation reaction supported the contention that monooxygen insertion is mediated by an active-site process. Experiments with 3-[ 2 H] indene indicated that equilibration between C-1 and C-3 occurred prior to the formation of the carbon-oxygen bond to yield 1-indenol. Naphthalene dioxygenase also oxidized indan to 1-indanol, which suggested that benzylic monoxygenation may be typical of this group of dioxygenases

  12. Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria.

    Science.gov (United States)

    Bernardini, Giulia; Laschi, Marcella; Geminiani, Michela; Braconi, Daniela; Vannuccini, Elisa; Lupetti, Pietro; Manetti, Fabrizio; Millucci, Lia; Santucci, Annalisa

    2015-09-01

    Alkaptonuria is an ultra-rare autosomal recessive disease developed from the lack of homogentisate 1,2-dioxygenase (HGD) activity, causing an accumulation in connective tissues of homogentisic acid (HGA) and its oxidized derivatives in polymerized form. The deposition of ochronotic pigment has been so far attributed to homogentisic acid produced by the liver, circulating in the blood, and accumulating locally. In the present paper, we report the expression of HGD in the brain. Mouse and human brain tissues were positively tested for HGD gene expression by western blotting. Furthermore, HGD expression was confirmed in human neuronal cells that also revealed the presence of six HGD molecular species. Moreover, once cultured in HGA excess, human neuronal cells produced ochronotic pigment and amyloid. Our findings indicate that alkaptonuric brain cells produce the ochronotic pigment in loco and this may contribute to induction of neurological complications.

  13. Degradation of phenanthrene and pyrene using genetically engineered dioxygenase producing Pseudomonas putida in soil

    Directory of Open Access Journals (Sweden)

    Mardani Gashtasb

    2016-01-01

    Full Text Available Bioremediation use to promote degradation and/or removal of contaminants into nonhazardous or less-hazardous substances from the environment using microbial metabolic ability. Pseudomonas spp. is one of saprotrophic soil bacterium and can be used for biodegradation of polycyclic aromatic hydrocarbons (PAHs but this activity in most species is weak. Phenanthrene and pyrene could associate with a risk of human cancer development in exposed individuals. The aim of the present study was application of genetically engineered P. putida that produce dioxygenase for degradation of phenanthrene and pyrene in spiked soil using high-performance liquid chromatography (HPLC method. The nahH gene that encoded catechol 2,3-dioxygenase (C23O was cloned into pUC18 and pUC18-nahH recombinant vector was generated and transformed into wild P. putida, successfully. The genetically modified and wild types of P. putida were inoculated in soil and pilot plan was prepared. Finally, degradation of phenanthrene and pyrene by this bacterium in spiked soil were evaluated using HPLC measurement technique. The results were showed elimination of these PAH compounds in spiked soil by engineered P. putida comparing to dishes containing natural soil with normal microbial flora and inoculated autoclaved soil by wild type of P. putida were statistically significant (p0.05 but it was few impact on this process (more than 2%. Additional and verification tests including catalase, oxidase and PCR on isolated bacteria from spiked soil were indicated that engineered P. putida was alive and functional as well as it can affect on phenanthrene and pyrene degradation via nahH gene producing. These findings indicated that genetically engineered P. putida generated in this work via producing C23O enzyme can useful and practical for biodegradation of phenanthrene and pyrene as well as petroleum compounds in polluted environments.

  14. Induction of 9-cis-epoxycarotenoid dioxygenase in Arabidopsis thaliana seeds enhances seed dormancy.

    Science.gov (United States)

    Martínez-Andújar, Cristina; Ordiz, M Isabel; Huang, Zhonglian; Nonogaki, Mariko; Beachy, Roger N; Nonogaki, Hiroyuki

    2011-10-11

    Full understanding of mechanisms that control seed dormancy and germination remains elusive. Whereas it has been proposed that translational control plays a predominant role in germination, other studies suggest the importance of specific gene expression patterns in imbibed seeds. Transgenic plants were developed to permit conditional expression of a gene encoding 9-cis-epoxycarotenoid dioxygenase 6 (NCED6), a rate-limiting enzyme in abscisic acid (ABA) biosynthesis, using the ecdysone receptor-based plant gene switch system and the ligand methoxyfenozide. Induction of NCED6 during imbibition increased ABA levels more than 20-fold and was sufficient to prevent seed germination. Germination suppression was prevented by fluridone, an inhibitor of ABA biosynthesis. In another study, induction of the NCED6 gene in transgenic seeds of nondormant mutants tt3 and tt4 reestablished seed dormancy. Furthermore, inducing expression of NCED6 during seed development suppressed vivipary, precocious germination of developing seeds. These results indicate that expression of a hormone metabolism gene in seeds can be a sole determinant of dormancy. This study opens the possibility of developing a robust technology to suppress or promote seed germination through engineering pathways of hormone metabolism.

  15. Polychlorinated biphenyls in honey bees

    Energy Technology Data Exchange (ETDEWEB)

    Morse, R.A.; Culliney, T.W.; Gutenmann, W.H.; Littman, C.B.; Lisk, D.J.

    1987-02-01

    Honey bees (Apis mellifera L.) may traverse a radius of several miles from their hives and contact innumerable surfaces during their collection of nectar, pollen, propolis and water. In the process, they may become contaminated with surface constituents which are indicative of the type of environmental pollution in their particular foraging area. Honey has also been analyzed as a possible indicator of heavy metal pollution. Insecticides used in the vicinity of bee hives have been found in bees and honey. It has been recently reported that appreciable concentrations of polychlorinated biphenyls (PCBs) have been found in honey bees sampled throughout Connecticut. In the work reported here, an analytical survey was conducted on PCBs in honey bees, honey, propolis and related samples in several states to learn the extent of contamination and possible sources.

  16. Probing the molecular determinants of aniline dioxygenase substrate specificity by saturation mutagenesis.

    Science.gov (United States)

    Ang, Ee L; Obbard, Jeffrey P; Zhao, Huimin

    2007-02-01

    Aniline dioxygenase is a multicomponent Rieske nonheme-iron dioxygenase enzyme isolated from Acinetobacter sp. strain YAA. Saturation mutagenesis of the substrate-binding pocket residues, which were identified using a homology model of the alpha subunit of the terminal dioxygenase (AtdA3), was used to probe the molecular determinants of AtdA substrate specificity. The V205A mutation widened the substrate specificity of aniline dioxygenase to include 2-isopropylaniline, for which the wild-type enzyme has no activity. The V205A mutation also made 2-isopropylaniline a better substrate for the enzyme than 2,4-dimethylaniline, a native substrate of the wild-type enzyme. The I248L mutation improved the activity of aniline dioxygenase against aniline and 2,4-dimethylaniline approximately 1.7-fold and 2.1-fold, respectively. Thus, it is shown that the alpha subunit of the terminal dioxygenase indeed plays a part in the substrate specificity as well as the activity of aniline dioxygenase. Interestingly, the equivalent residues of V205 and I248 have not been previously reported to influence the substrate specificity of other Rieske dioxygenases. These results should facilitate future engineering of the enzyme for bioremediation and industrial applications.

  17. INDOLEAMINE 2,3-DIOXYGENASE (IDO AND IMMUNE TOLERANCE

    Directory of Open Access Journals (Sweden)

    Coma-del-Corral MJ

    2013-09-01

    Full Text Available SUMMARY: Indoleamine 2,3-dioxygenase (IDO is an intracellular and extrahepatic enzyme predominantly found in many cells, especially macrophages. Tryptophan degradation generates kynurenine, and this pathway of tryptophan metabolism is an effective mechanism for modulating the immune response. The IDO facilitates immune tolerance and is one of the main actors involved in the inhibition of cell proliferation, including activated T cells. IDO induces production of reactive oxygen species (ROS and nitric oxide (NO radicals. Several pathways involved in the regulation of immune response are regulated by redox mechanisms. Reactive oxygen and nitrogen species (ROS-RNS and other redox active molecules play key roles in immunity.

  18. Differential spatio-temporal expression of carotenoid cleavage dioxygenases regulates apocarotenoid fluxes during AM symbiosis.

    Science.gov (United States)

    López-Ráez, Juan A; Fernández, Iván; García, Juan M; Berrio, Estefanía; Bonfante, Paola; Walter, Michael H; Pozo, María J

    2015-01-01

    Apocarotenoids are a class of compounds that play important roles in nature. In recent years, a prominent role for these compounds in arbuscular mycorrhizal (AM) symbiosis has been shown. They are derived from carotenoids by the action of the carotenoid cleavage dioxygenase (CCD) enzyme family. In the present study, using tomato as a model, the spatio-temporal expression pattern of the CCD genes during AM symbiosis establishment and functioning was investigated. In addition, the levels of the apocarotenoids strigolactones (SLs), C13 α-ionol and C14 mycorradicin (C13/C14) derivatives were analyzed. The results suggest an increase in SLs promoted by the presence of the AM fungus at the early stages of the interaction, which correlated with an induction of the SL biosynthesis gene SlCCD7. At later stages, induction of SlCCD7 and SlCCD1 expression in arbusculated cells promoted the production of C13/C14 apocarotenoid derivatives. We show here that the biosynthesis of apocarotenoids during AM symbiosis is finely regulated throughout the entire process at the gene expression level, and that CCD7 constitutes a key player in this regulation. Once the symbiosis is established, apocarotenoid flux would be turned towards the production of C13/C14 derivatives, thus reducing SL biosynthesis and maintaining a functional symbiosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Laboratory evaluation of polychlorinated biphenyls ...

    Science.gov (United States)

    Effectiveness and limitations of the encapsulation method for reducing polychlorinated biphenyls (PCBs) concentrations in indoor air and contaminated surface have been evaluated in the laboratory study. Ten coating materials such as epoxy and polyurethane coatings, latex paint, and petroleum-based paint were tested in small environmental chambers to rank the encapsulants by their resistance to PCB sorption and estimate the key parameters required by a barrier model. Wipe samples were collected from PCB contaminated surface encapsulated with the coating materials to rank the encapsulants by their resistance to PCB migration from the source. A barrier model was used to calculate the PCB concentrations in the sources and the encapsulant layers, and at the exposed surfaces of the encapsulant and in the room air at different times. The performance of the encapsulants was ranked by those concentrations and PCB percent reductions. Overall, the three epoxy coatings performed better than the other coatings. Both the experimental results and the mathematical modeling showed that selecting proper encapsulants can effectively reduce the PCB concentrations at the exposed surfaces. The encapsulation method is most effective for contaminated surfaces that contain low levels of PCBs. This study answers some of these questions by using a combination of laboratory testing and mathematical modeling. The results should be useful to mitigation engineers, building owners and managers

  20. Optical detection of polychlorinated biphenyls

    Science.gov (United States)

    Kuncova, Gabriela; Berkova, Daniela; Burkhard, Jiri; Demnerova, Katerina; Pazlarova, Jarmila; Triska, Jan; Vrchotova, Nadezda

    1999-12-01

    In this paper we describe the detection of polychlorinated biphenyls (PCBs) which is based on the measurement of changes of optical absorption at 400 nm of the medium in an aerobic bioreactor with immobilized cells Pseudomonas species 2. The rate of production, composition and the concentration of yellow intermediates are influenced by concentration and composition of PCB mixtures, concentration of cells and by the methods of immobilization. The method was applied in the detection of commercial mixture D103. It was found that the advantageous carriers were inorganic or organic-inorganic matrices, which sorbed PCBs and a cell outgrowth from their surface was low. In water contaminated with transformer oil and chlorinated hydrocarbons the detection limit is 10-2 gD103/kg. In transformer oil the upper limit for degradation of D103 by sodium dehalogenation (1.5 gD103 /kgoil) was determined also in the presence of the same concentration of trichloroethylene. The employment to of a liquid core waveguide spectrophotometer instead of a diode array spectrophotometer increased the sensitivity of the measurement of yellow intermediates by a factor of 100. An extrinsic fiber-optic sensor was used for in-situ measurement during biodegradation of PCBs in bioreactors.

  1. Cysteine dioxygenase type 1 promotes adipogenesis via interaction with peroxisome proliferator-activated receptor gamma

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Peng; Chen, Yi; Ji, Ning; Lin, Yunfeng; Yuan, Quan; Ye, Ling; Chen, Qianming, E-mail: qmchen@scu.edu.cn

    2015-02-27

    Mammalian cysteine dioxygenase type 1 (CDO1) is an essential enzyme for taurine biosynthesis and the biodegradation of toxic cysteine. As previously suggested, Cdo1 may be a marker of liposarcoma progression and adipogenic differentiation, but the role of Cdo1 in adipogenesis has yet been reported. In this study, we found that the expression of Cdo1 is dramatically elevated during adipogenic differentiation of 3T3-L1 pre-adipocytes and mouse bone marrow-derived mesenchymal stem cells (mBMSCs). Conversely, knockdown of Cdo1 inhibited expression of adipogenic specific genes and lipid droplet formation in 3T3-L1 cells and mBMSCs. Mechanistically, we found Cdo1 interacted with Pparγ in response to adipogenic stimulus. Further, depletion of Cdo1 reduced the recruitment of Pparγ to the promoters of C/EBPα and Fabp4. Collectively, our finding indicates that Cdo1 may be a co-activator of Pparγ in adipogenesis, and may contribute to the development of disease associated with excessive adipose tissue. - Highlights: • Cdo1expression is highly up-regulated during adipogenic differentiation of 3T3-L1 and mBMSCs. • Depletion of Cdo1 inhibited expression of adipogenic specific genes and lipid droplet formation. • Cdo1interacts with Pparγ during adipogenesis. • Knockdown of Cdo1 inhibited Pparγ binding to the promoters of C/EBPα and Fabp4.

  2. Microbial transformation and degradation of polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Field, Jim A. [Department of Chemical and Environmental Engineering, University of Arizona, PO Box 210011, Tucson, AZ 85721 (United States)], E-mail: jimfield@email.arizona.edu; Sierra-Alvarez, Reyes [Department of Chemical and Environmental Engineering, University of Arizona, PO Box 210011, Tucson, AZ 85721 (United States)

    2008-09-15

    This paper reviews the potential of microorganisms to transform polychlorinated biphenyls (PCBs). In anaerobic environments, higher chlorinated biphenyls can undergo reductive dehalogenation. Meta- and para-chlorines in PCB congeners are more susceptible to dechlorination than ortho-chlorines. Anaerobes catalyzing PCB dechlorination have not been isolated in pure culture but there is strong evidence from enrichment cultures that some Dehalococcoides spp. and other microorganisms within the Chloroflexi phylum can grow by linking the oxidation of H{sub 2} to the reductive dechlorination of PCBs. Lower chlorinated biphenyls can be co-metabolized aerobically. Some aerobes can also grow by utilizing PCB congeners containing only one or two chlorines as sole carbon/energy source. An example is the growth of Burkholderia cepacia by transformation of 4-chlorobiphenyl to chlorobenzoates. The latter compounds are susceptible to aerobic mineralization. Higher chlorinated biphenyls therefore are potentially fully biodegradable in a sequence of reductive dechlorination followed by aerobic mineralization of the lower chlorinated products. - Higher chlorinated biphenyls are potentially fully biodegradable in a sequence of anaerobic reductive dechlorination followed by aerobic mineralization of the lower chlorinated products.

  3. Microbial transformation and degradation of polychlorinated biphenyls

    International Nuclear Information System (INIS)

    Field, Jim A.; Sierra-Alvarez, Reyes

    2008-01-01

    This paper reviews the potential of microorganisms to transform polychlorinated biphenyls (PCBs). In anaerobic environments, higher chlorinated biphenyls can undergo reductive dehalogenation. Meta- and para-chlorines in PCB congeners are more susceptible to dechlorination than ortho-chlorines. Anaerobes catalyzing PCB dechlorination have not been isolated in pure culture but there is strong evidence from enrichment cultures that some Dehalococcoides spp. and other microorganisms within the Chloroflexi phylum can grow by linking the oxidation of H 2 to the reductive dechlorination of PCBs. Lower chlorinated biphenyls can be co-metabolized aerobically. Some aerobes can also grow by utilizing PCB congeners containing only one or two chlorines as sole carbon/energy source. An example is the growth of Burkholderia cepacia by transformation of 4-chlorobiphenyl to chlorobenzoates. The latter compounds are susceptible to aerobic mineralization. Higher chlorinated biphenyls therefore are potentially fully biodegradable in a sequence of reductive dechlorination followed by aerobic mineralization of the lower chlorinated products. - Higher chlorinated biphenyls are potentially fully biodegradable in a sequence of anaerobic reductive dechlorination followed by aerobic mineralization of the lower chlorinated products

  4. 21 CFR 109.30 - Tolerances for polychlorinated biphenyls (PCB's).

    Science.gov (United States)

    2010-04-01

    ... Tolerances for polychlorinated biphenyls (PCB's). (a) Polychlorinated biphenyls (PCB's) are toxic, industrial chemicals. Because of their widespread, uncontrolled industrial applications, PCB's have become a persistent... unavoidable environmental or industrial contaminants are established for a sufficient period of time following...

  5. 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Chemical Biology to Agrochemicals.

    Science.gov (United States)

    Ndikuryayo, Ferdinand; Moosavi, Behrooz; Yang, Wen-Chao; Yang, Guang-Fu

    2017-10-04

    The development of new herbicides is receiving considerable attention to control weed biotypes resistant to current herbicides. Consequently, new enzymes are always desired as targets for herbicide discovery. 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an enzyme engaged in photosynthetic activity and catalyzes the transformation of 4-hydroxyphenylpyruvic acid (HPPA) into homogentisic acid (HGA). HPPD inhibitors constitute a promising area of discovery and development of innovative herbicides with some advantages, including excellent crop selectivity, low application rates, and broad-spectrum weed control. HPPD inhibitors have been investigated for agrochemical interests, and some of them have already been commercialized as herbicides. In this review, we mainly focus on the chemical biology of HPPD, discovery of new potential inhibitors, and strategies for engineering transgenic crops resistant to current HPPD-inhibiting herbicides. The conclusion raises some relevant gaps for future research directions.

  6. Mechanism of S-oxygenation by a cysteine dioxygenase model complex

    OpenAIRE

    Kumar, Devesh; Sastry, G. Narahari; Goldberg, David P.; de Visser, Sam P.

    2011-01-01

    In this work we present the first computational study on a biomimetic cysteine dioxygenase model complex, [FeII(LN3S)]+ where LN3S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O2 was examined by density functional theory (DFT) methods, and compared to results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet and quintet spi...

  7. Structures of the multicomponent Rieske non-heme iron toluene 2, 3-dioxygenase enzyme system

    Energy Technology Data Exchange (ETDEWEB)

    Friemann, Rosmarie [Department of Molecular Biology, Swedish University of Agricultural Sciences, Box 590, 751 24 Uppsala (Sweden); Lee, Kyoung [Department of Microbiology, Changwon National University, Changwon, Kyoungnam 641-773 (Korea, Republic of); Department of Microbiology, The University of Iowa, Iowa City, Iowa 52242 (United States); Brown, Eric N. [Department of Biochemistry, The University of Iowa, Iowa City, Iowa 52242 (United States); Gibson, David T. [Department of Microbiology, The University of Iowa, Iowa City, Iowa 52242 (United States); Eklund, Hans [Department of Molecular Biology, Swedish University of Agricultural Sciences, Box 590, 751 24 Uppsala (Sweden); Ramaswamy, S., E-mail: s-ramaswamy@uiowa.edu [Department of Biochemistry, The University of Iowa, Iowa City, Iowa 52242 (United States); Department of Molecular Biology, Swedish University of Agricultural Sciences, Box 590, 751 24 Uppsala (Sweden)

    2009-01-01

    The crystal structures of the three-component toluene 2, 3-dioxygenase system provide a model for electron transfer among bacterial Rieske non-heme iron dioxygenases. Bacterial Rieske non-heme iron oxygenases catalyze the initial hydroxylation of aromatic hydrocarbon substrates. The structures of all three components of one such system, the toluene 2, 3-dioxygenase system, have now been determined. This system consists of a reductase, a ferredoxin and a terminal dioxygenase. The dioxygenase, which was cocrystallized with toluene, is a heterohexamer containing a catalytic and a structural subunit. The catalytic subunit contains a Rieske [2Fe–2S] cluster and mononuclear iron at the active site. This iron is not strongly bound and is easily removed during enzyme purification. The structures of the enzyme with and without mononuclear iron demonstrate that part of the structure is flexible in the absence of iron. The orientation of the toluene substrate in the active site is consistent with the regiospecificity of oxygen incorporation seen in the product formed. The ferredoxin is Rieske type and contains a [2Fe–2S] cluster close to the protein surface. The reductase belongs to the glutathione reductase family of flavoenzymes and consists of three domains: an FAD-binding domain, an NADH-binding domain and a C-terminal domain. A model for electron transfer from NADH via FAD in the reductase and the ferredoxin to the terminal active-site mononuclear iron of the dioxygenase is proposed.

  8. Isolation and Functional Characterization of Carotenoid Cleavage Dioxygenase-1 from Laurus nobilis L. (Bay Laurel) Fruits.

    Science.gov (United States)

    Yahyaa, Mosaab; Berim, Anna; Isaacson, Tal; Marzouk, Sally; Bar, Einat; Davidovich-Rikanati, Rachel; Lewinsohn, Efraim; Ibdah, Mwafaq

    2015-09-23

    Bay laurel (Laurus nobilis L.) is an agriculturally important tree used in food, drugs, and the cosmetics industry. Many of the health beneficial properties of bay laurel are due to volatile terpene metabolites that they contain, including various norisoprenoids. Despite their importance, little is known about the norisoprenoid biosynthesis in Laurus nobilis fruits. We found that the volatile norisoprenoids 6-methyl-5-hepten-2-one, pseudoionone, and β-ionone accumulated in Laurus nobilis fruits in a pattern reflecting their carotenoid content. A full-length cDNA encoding a potential carotenoid cleavage dioxygenase (LnCCD1) was isolated. The LnCCD1 gene was overexpressed in Escherichia coli, and recombinant protein was assayed for its cleavage activity with an array of carotenoid substrates. The LnCCD1 protein was able to cleave a variety of carotenoids at the 9,10 (9',10') and 5,6 (5',6') positions to produce 6-methyl-5-hepten-2-one, pseudoionone, β-ionone, and α-ionone. Our results suggest a role for LnCCD1 in Laurus nobilis fruit flavor biosynthesis.

  9. Characterization and subcellular compartmentation of recombinant 4-hydroxyphenylpyruvate dioxygenase from Arabidopsis in transgenic tobacco.

    Science.gov (United States)

    Garcia, I; Rodgers, M; Pepin, R; Hsieh, T F; Matringe, M

    1999-04-01

    4-Hydroxyphenylpyruvate dioxygenase (4HPPD) catalyzes the formation of homogentisate (2,5-dihydroxyphenylacetate) from p-hydroxyphenylpyruvate and molecular oxygen. In plants this enzyme activity is involved in two distinct metabolic processes, the biosynthesis of prenylquinones and the catabolism of tyrosine. We report here the molecular and biochemical characterization of an Arabidopsis 4HPPD and the compartmentation of the recombinant protein in chlorophyllous tissues. We isolated a 1508-bp cDNA with one large open reading frame of 1338 bp. Southern analysis strongly suggested that this Arabidopsis 4HPPD is encoded by a single-copy gene. We investigated the biochemical characteristics of this 4HPPD by overproducing the recombinant protein in Escherichia coli JM105. The subcellular localization of the recombinant 4HPPD in chlorophyllous tissues was examined by overexpressing its complete coding sequence in transgenic tobacco (Nicotiana tabacum), using Agrobacterium tumefaciens transformation. We performed western analyses for the immunodetection of protein extracts from purified chloroplasts and total leaf extracts and for the immunocytochemistry on tissue sections. These analyses clearly revealed that 4HPPD was confined to the cytosol compartment, not targeted to the chloroplast. Western analyses confirmed the presence of a cytosolic form of 4HPPD in cultured green Arabidopsis cells.

  10. Plant enzymes in metabolism of polychlorinated biphenyls

    Czech Academy of Sciences Publication Activity Database

    Chromá, L.; Moeder, M.; Kučerová, P.; Macek, Tomáš; Macková, M.

    2003-01-01

    Roč. 12, č. 3 (2003), s. 291-295 ISSN 1018-4619 R&D Projects: GA MŠk ME 498 Institutional research plan: CEZ:AV0Z4055905 Keywords : polychlorinated biphenyls * plants * peroxidases Subject RIV: CE - Biochemistry Impact factor: 0.325, year: 2003

  11. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

    van Noort, P.C.M.; Haftka, J.J.H.; Parsons, J.R.

    2010-01-01

    This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air−n-hexadecane and n-octanol−water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was

  12. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

    Noort, van P.C.M.; Haftka, J.J.H.; Parsons, J.R.

    2010-01-01

    This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air-n-hexadecane and n-octanol-water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was

  13. Activation of ethylene-responsive p-hydroxyphenylpyruvate dioxygenase leads to increased tocopherol levels during ripening in mango

    Science.gov (United States)

    Singh, Rajesh K.; Ali, Sharique A.; Nath, Pravendra; Sane, Vidhu A.

    2011-01-01

    Mango is characterized by high tocopherol and carotenoid content during ripening. From a cDNA screen of differentially expressing genes during mango ripening, a full-length p-hydroxyphenylpyruvate dioxygenase (MiHPPD) gene homologue was isolated that encodes a key enzyme in the biosynthesis of tocopherols. The gene encoded a 432-amino-acid protein. Transcript analysis during different stages of ripening revealed that the gene is ripening related and rapidly induced by ethylene. The increase in MiHPPD transcript accumulation was followed by an increase in tocopherol levels during ripening. The ripening-related increase in MiHPPD expression was also seen in response to abscisic acid and to alesser extent to indole-3-acetic acid. The expression of MiHPPD was not restricted to fruits but was also seen in other tissues such as leaves particularly during senescence. The strong ethylene induction of MiHPPD was also seen in young leaves indicating that ethylene induction of MiHPPD is tissue independent. Promoter analysis of MiHPPD gene in tomato discs and leaves of stable transgenic lines of Arabidopsis showed that the cis elements for ripening-related, ethylene-responsive, and senescence-related expression resided within the 1590 nt region upstream of the ATG codon. Functionality of the gene was demonstrated by the ability of the expressed protein in bacteria to convert p-hydroxyphenylpyruvate to homogentisate. These results provide the first evidence for HPPD expression during ripening of a climacteric fruit. PMID:21430290

  14. Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase

    Energy Technology Data Exchange (ETDEWEB)

    Pantouris, Georgios; Mowat, Christopher G., E-mail: C.G.Mowat@ed.ac.uk

    2014-01-03

    Highlights: •∼2800 National Cancer Institute USA compounds have been screened as potential inhibitors of TDO and/or IDO. •Seven compounds with anti-tumour properties have been identified as potent inhibitors. •NSC 36398 (taxifolin, dihydroquercetin) is selective for TDO with a K{sub i} of 16 M. •This may help further our understanding of the role of TDO in cancer. -- Abstract: The involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors of TDO that may potentially be developed for therapeutic use. In this work we have screened ∼2800 compounds from the library of the National Cancer Institute USA and identified seven potent inhibitors of TDO with inhibition constants in the nanomolar or low micromolar range. All seven have antitumour properties, killing various cancer cell lines. For comparison, the inhibition potencies of these compounds were tested against IDO and their inhibition constants are reported. Interestingly, this work reveals that NSC 36398 (dihydroquercetin, taxifolin), with an in vitro inhibition constant of ∼16 μM, is the first TDO-selective inhibitor reported.

  15. Engineering Non-Heme Mono- and Dioxygenases for Biocatalysis

    Directory of Open Access Journals (Sweden)

    Adi Dror

    2012-09-01

    Full Text Available Oxygenases are ubiquitous enzymes that catalyze the introduction of one or two oxygen atoms to unreactive chemical compounds. They require reduction equivalents from NADH or NADPH and comprise metal ions, metal ion complexes, or coenzymes in their active site. Thus, for industrial purposes, oxygenases are most commonly employed using whole cell catalysis, to alleviate the need for co-factor regeneration. Biotechnological applications include bioremediation, chiral synthesis, biosensors, fine chemicals, biofuels, pharmaceuticals, food ingredients and polymers. Controlling activity and selectivity of oxygenases is therefore of great importance and of growing interest to the scientific community. This review focuses on protein engineering of non-heme monooxygenases and dioxygenases for generating improved or novel functionalities. Rational mutagenesis based on x-ray structures and sequence alignment, as well as random methods such as directed evolution, have been utilized. It is concluded that knowledge-based protein engineering accompanied with targeted libraries, is most efficient for the design and tuning of biocatalysts towards novel substrates and enhanced catalytic activity while minimizing the screening efforts.

  16. Crystal Structure of Mammalian Cysteine dioxygenase: A Novel Mononuclear Iron Center for Cysteine Thiol Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons,C.; Liu, Q.; Huang, Q.; Hao, Q.; Begley, T.; Karplus, P.; Stipanuk, M.

    2006-01-01

    Cysteine dioxygenase is a mononuclear iron-dependent enzyme responsible for the oxidation of cysteine with molecular oxygen to form cysteinesulfinate. This reaction commits cysteine to either catabolism to sulfate and pyruvate or to the taurine biosynthetic pathway. Cysteine dioxygenase is a member of the cupin superfamily of proteins. The crystal structure of recombinant rat cysteine dioxygenase has been determined to 1.5 Angstroms resolution, and these results confirm the canonical cupin {beta}-sandwich fold and the rare cysteinyl-tyrosine intramolecular crosslink (between Cys93 and Tyr157) seen in the recently reported murine cysteine dioxygenase structure. In contrast to the catalytically inactive mononuclear Ni(II) metallocenter present in the murine structure, crystallization of a catalytically competent preparation of rat cysteine dioxygenase revealed a novel tetrahedrally coordinated mononuclear iron center involving three histidines (His86, His88, and His140) and a water molecule. Attempts to acquire a structure with bound ligand using either co-crystallization or soaks with cysteine revealed the formation of a mixed disulfide involving Cys164 near the active site, which may explain previously observed substrate inhibition. This work provides a framework for understanding the molecular mechanisms involved in thiol dioxygenation and sets the stage for exploring the chemistry of both the novel mononuclear iron center and the catalytic role of the cysteinyl-tyrosine linkage.

  17. EPR characterization of the mononuclear Cu-containing Aspergillus japonicus quercetin 2,3-dioxygenase reveals dramatic changes upon anaerobic binding of substrates

    NARCIS (Netherlands)

    Kooter, Ingeborg M.; Steiner, Roberto A.; Dijkstra, Bauke W.; Noort, Paula I. van; Egmond, Maarten R.; Huber, Martina

    Quercetin 2,3-dioxygenase (2,3QD) is a copper-containing dioxygenase that catalyses the oxidation of the flavonol quercetin to 2-protocatechuoylphloroglucinol carboxylic acid with concomitant production of carbon monoxide. In contrast to iron dioxygenases, very little is known about copper

  18. Exposure Monitoring and Risk Assessment of Biphenyl in the Workplace

    OpenAIRE

    Kim, Hyeon-Yeong; Shin, Sae-Mi; Ham, Miran; Lim, Cheol-Hong; Byeon, Sang-Hoon

    2015-01-01

    This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable ma...

  19. Prokaryotic Homologs of the Eukaryotic 3-Hydroxyanthranilate 3,4-Dioxygenase and 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase in the 2-Nitrobenzoate Degradation Pathway of Pseudomonas fluorescens Strain KU-7†

    OpenAIRE

    Muraki, Takamichi; Taki, Masami; Hasegawa, Yoshie; Iwaki, Hiroaki; Lau, Peter C. K.

    2003-01-01

    The 2-nitrobenzoic acid degradation pathway of Pseudomonas fluorescens strain KU-7 proceeds via a novel 3-hydroxyanthranilate intermediate. In this study, we cloned and sequenced a 19-kb DNA locus of strain KU-7 that encompasses the 3-hydroxyanthranilate meta-cleavage pathway genes. The gene cluster, designated nbaEXHJIGFCDR, is organized tightly and in the same direction. The nbaC and nbaD gene products were found to be novel homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase a...

  20. Evolutionarily distinct carotenoid cleavage dioxygenases are responsible for crocetin production in Buddleja davidii.

    Science.gov (United States)

    Ahrazem, Oussama; Diretto, Gianfranco; Argandoña, Javier; Rubio-Moraga, Ángela; Julve, José Manuel; Orzáez, Diego; Granell, Antonio; Gómez-Gómez, Lourdes

    2017-07-20

    Crocetin, one of the few colored apocarotenoids known in nature, is present in flowers and fruits and has long been used medicinally and as a colorant. Saffron is the main source of crocetin, although a few other plants produce lower amounts of this apocarotenoid. Notably, Buddleja davidii accumulates crocetin in its flowers. Recently, a carotenoid dioxygenase cleavage enzyme, CCD2, has been characterized as responsible for crocetin production in Crocus species. We searched for CCD2 homologues in B. davidii and identified several CCD enzymes from the CCD1 and CCD4 subfamilies. Unexpectedly, two out of the three CCD4 enzymes, namely BdCCD4.1 and BdCCD4.3, showed 7,8;7',8' activity in vitro and in vivo over zeaxanthin. In silico analyses of these enzymes and CCD2 allowed the determination of key residues for this activity. Both BdCCD4 genes are highly expressed during flower development and transcripts levels parallel the accumulation of crocins in the petals. Phylogenetic analysis showed that BdCCD4.2 grouped with almost all the characterized CCD4 enzymes, while BdCCD4.1 and BdCCD4.3 form a new sub-cluster together with CCD4 enzymes from certain Lamiales species. The present study indicates that convergent evolution led to the acquisition of 7,8;7',8' apocarotenoid cleavage activity in two separate CCD enzyme families. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Study of 'Redhaven' peach and its white-fleshed mutant suggests a key role of CCD4 carotenoid dioxygenase in carotenoid and norisoprenoid volatile metabolism

    Directory of Open Access Journals (Sweden)

    Tartarini Stefano

    2011-01-01

    Full Text Available Abstract Background Carotenoids are plant metabolites which are not only essential in photosynthesis but also important quality factors in determining the pigmentation and aroma of flowers and fruits. To investigate the regulation of carotenoid metabolism, as related to norisoprenoids and other volatile compounds in peach (Prunus persica L. Batsch., and the role of carotenoid dioxygenases in determining differences in flesh color phenotype and volatile composition, the expression patterns of relevant carotenoid genes and metabolites were studied during fruit development along with volatile compound content. Two contrasted cultivars, the yellow-fleshed 'Redhaven' (RH and its white-fleshed mutant 'Redhaven Bianca' (RHB were examined. Results The two genotypes displayed marked differences in the accumulation of carotenoid pigments in mesocarp tissues. Lower carotenoid levels and higher levels of norisoprenoid volatiles were observed in RHB, which might be explained by differential activity of carotenoid cleavage dioxygenase (CCD enzymes. In fact, the ccd4 transcript levels were dramatically higher at late ripening stages in RHB with respect to RH. The two genotypes also showed differences in the expression patterns of several carotenoid and isoprenoid transcripts, compatible with a feed-back regulation of these transcripts. Abamine SG - an inhibitor of CCD enzymes - decreased the levels of both isoprenoid and non-isoprenoid volatiles in RHB fruits, indicating a complex regulation of volatile production. Conclusions Differential expression of ccd4 is likely to be the major determinant in the accumulation of carotenoids and carotenoid-derived volatiles in peach fruit flesh. More in general, dioxygenases appear to be key factors controlling volatile composition in peach fruit, since abamine SG-treated 'Redhaven Bianca' fruits had strongly reduced levels of norisoprenoids and other volatile classes. Comparative functional studies of peach carotenoid

  2. Optimizing Polychlorinated Biphenyl Degradation by Flavonoid-Induced Cells of the Rhizobacterium Rhodococcus erythropolis U23A.

    Directory of Open Access Journals (Sweden)

    Thi Thanh My Pham

    Full Text Available There is evidence that many plant secondary metabolites may act as signal molecules to trigger the bacterial ability to metabolize polychlorinated biphenyls (PCBs during the rhizoremediation process. However, the bases for the PCB rhizoremediation process are still largely unknown. The rhizobacterium Rhodococcus erythropolis U23A is unable to use flavanone as a growth substrate. However, on the basis of an assay that monitors the amount of 4-chlorobenzoate produced from 4-chlorobiphenyl by cells grown co-metabolically on flavanone plus sodium acetate, this flavonoid was previously found to be a potential inducer of the U23A biphenyl catabolic pathway. In this work, and using the same assay, we identified ten other flavonoids that did not support growth, but that acted as inducers of the U23A biphenyl pathway, and we confirmed flavonoid induction of the biphenyl catabolic pathway using quantitative real-time polymerase chain reaction (RT-qPCR on the bphA gene. We also examined the effect of the growth co-substrate on flavonoid induction. Sodium acetate was replaced by glucose, mannose, sucrose, or mannitol, which are sugars found in plant root exudates. The data showed that the level of induction of strain U23A biphenyl-degrading enzymes was significantly influenced by the nature and concentration of the flavonoid in the growth medium, as well as by the substrate used for growth. Sucrose allowed for an optimal induction response for most flavonoids. Some flavonoids, such as flavone and isoflavone, were better inducers of the biphenyl catabolic enzymes than biphenyl itself. We also found that all flavonoids tested in this work were metabolized by strain U23A during co-metabolic growth, but that the metabolite profiles, as well as the level of efficiency of degradation, differed for each flavonoid. To obtain insight into how flavonoids interact with strain U23A to promote polychlorinated biphenyl (PCB degradation, we determined the concentration of

  3. Petunia hybrida CAROTENOID CLEAVAGE DIOXYGENASE7 is involved in the production of negative and positive branching signals in petunia.

    Science.gov (United States)

    Drummond, Revel S M; Martínez-Sánchez, N Marcela; Janssen, Bart J; Templeton, Kerry R; Simons, Joanne L; Quinn, Brian D; Karunairetnam, Sakuntala; Snowden, Kimberley C

    2009-12-01

    One of the key factors that defines plant form is the regulation of when and where branches develop. The diversity of form observed in nature results, in part, from variation in the regulation of branching between species. Two CAROTENOID CLEAVAGE DIOXYGENASE (CCD) genes, CCD7 and CCD8, are required for the production of a branch-suppressing plant hormone. Here, we report that the decreased apical dominance3 (dad3) mutant of petunia (Petunia hybrida) results from the mutation of the PhCCD7 gene and has a less severe branching phenotype than mutation of PhCCD8 (dad1). An analysis of the expression of this gene in wild-type, mutant, and grafted petunia suggests that in petunia, CCD7 and CCD8 are coordinately regulated. In contrast to observations in Arabidopsis (Arabidopsis thaliana), ccd7ccd8 double mutants in petunia show an additive phenotype. An analysis using dad3 or dad1 mutant scions grafted to wild-type rootstocks showed that when these plants produce adventitious mutant roots, branching is increased above that seen in plants where the mutant roots are removed. The results presented here indicate that mutation of either CCD7 or CCD8 in petunia results in both the loss of an inhibitor of branching and an increase in a promoter of branching.

  4. Transcriptional Response of Rhodococcus aetherivorans I24 to Polychlorinated Biphenyl-Contaminated Sediments

    KAUST Repository

    Puglisi, Edoardo

    2010-04-06

    We used a microarray targeting 3,524 genes to assess the transcriptional response of the actinomycete Rhodococcus aetherivorans I24 in minimal medium supplemented with various substrates (e. g., PCBs) and in both PCB-contaminated and non-contaminated sediment slurries. Relative to the reference condition (minimal medium supplemented with glucose), 408 genes were upregulated in the various treatments. In medium and in sediment, PCBs elicited the upregulation of a common set of 100 genes, including gene-encoding chaperones (groEL), a superoxide dismutase (sodA), alkyl hydroperoxide reductase protein C (ahpC), and a catalase/peroxidase (katG). Analysis of the R. aetherivorans I24 genome sequence identified orthologs of many of the genes in the canonical biphenyl pathway, but very few of these genes were upregulated in response to PCBs or biphenyl. This study is one of the first to use microarrays to assess the transcriptional response of a soil bacterium to a pollutant under conditions that more closely resemble the natural environment. Our results indicate that the transcriptional response of R. aetherivorans I24 to PCBs, in both medium and sediment, is primarily directed towards reducing oxidative stress, rather than catabolism. © 2010 Springer Science+Business Media, LLC.

  5. A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase

    Directory of Open Access Journals (Sweden)

    Christmas DM

    2011-07-01

    Full Text Available David M Christmas, JP Potokar, Simon JC DaviesAcademic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Bristol, UK A presentation relating to this manuscript was made by Dr David Christmas at the 9th International Meeting on Clinical Pharmacology in Psychiatry (9th IMCPP in Copenhagen, Denmark in September 2010Abstract: This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature. The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression. Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression. The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression. The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine. Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway.Keywords: depression, inflammation, indoleamine 2,3-dioxygenase, kynurenine, serotonin, tryptophan

  6. Draft Genome Sequence of Cupriavidus pauculus Strain KF709, a Biphenyl-Utilizing Bacterium Isolated from Biphenyl-Contaminated Soil.

    Science.gov (United States)

    Watanabe, Takahito; Yamazoe, Atsushi; Hosoyama, Akira; Fujihara, Hidehiko; Suenaga, Hikaru; Hirose, Jun; Futagami, Taiki; Goto, Masatoshi; Kimura, Nobutada; Furukawa, Kensuke

    2015-03-26

    We report the draft genome sequence of Cupriavidus pauculus strain KF709, which comprises 6,826,799 bp with 6,272 coding sequences. The strain KF709 utilizes biphenyl and degrades low-chlorinated biphenyls; however, it possesses fewer coding sequences involved in the degradation of aromatic compounds than other strains belonging to the Betaproteobacteria. Copyright © 2015 Watanabe et al.

  7. Draft Genome Sequence of Cupriavidus pauculus Strain KF709, a Biphenyl-Utilizing Bacterium Isolated from Biphenyl-Contaminated Soil

    OpenAIRE

    Watanabe, Takahito; Yamazoe, Atsushi; Hosoyama, Akira; Fujihara, Hidehiko; Suenaga, Hikaru; Hirose, Jun; Futagami, Taiki; Goto, Masatoshi; Kimura, Nobutada; Furukawa, Kensuke

    2015-01-01

    We report the draft genome sequence of Cupriavidus pauculus strain KF709, which comprises 6,826,799 bp with 6,272 coding sequences. The strain KF709 utilizes biphenyl and degrades low-chlorinated biphenyls; however, it possesses fewer coding sequences involved in the degradation of aromatic compounds than other strains belonging to the Betaproteobacteria.

  8. Isolation and identification of aerobic polychlorinated biphenyls degrading bacteria

    Directory of Open Access Journals (Sweden)

    Bibi Fatemeh Nabavi

    2013-01-01

    Full Text Available Aims: The purpose of this study was to isolate and identify aerobic polychlorinated biphenyls (PCBs degrading bacteria. Materials and Methods: This study was performed in lab scale aerobic sequencing batch biofilm reactor. Polyurethane foams were used as bio-carrier and synthetic wastewater was prepared with PCBs in transformer oil as the main substrate (20-700 μg/l and acetone as a solvent for PCBs as well as microelements. After achieving to adequate microbial population and acclimation of microorganisms to PCB compounds with high efficiency of PCB removal, identification of degrading microbial species was performed by 16s rRNA gene sequencing of isolated bacteria. Results: Gene sequencing results of the isolated bacteria showed that Rhodococcus spp., Pseudomonas spp., Pseudoxanthomonas spp., Agromyces spp., and Brevibacillus spp. were dominant PCB-degrading bacteria. Conclusion: PCB compounds can be degraded by some microorganisms under aerobic or anaerobic conditions or at least be reduced to low chlorinated congeners, despite their chemical stability and toxicity. Based on the results of the study, five bacterial species capable of degrading PCBs in transformer oil have been identified.

  9. Process for removing polychlorinated biphenyls from soil

    Science.gov (United States)

    Hancher, C.W.; Saunders, M.B.; Googin, J.M.

    1984-11-16

    The present invention relates to a method of removing polychlorinated biphenyls from soil. The polychlorinated biphenyls are extracted from the soil by employing a liquid organic solvent dispersed in water in the ratio of about 1:3 to 3:1. The organic solvent includes such materials as short-chain hydrocarbons including kerosene or gasoline which are immiscible with water and are nonpolar. The organic solvent has a greater affinity for the PCB's than the soil so as to extract the PCB's from the soil upon contact. The organic solvent phase is separated from the suspended soil and water phase and distilled for permitting the recycle of the organic solvent phase and the concentration of the PCB's in the remaining organic phase. The present process can be satisfactorily practiced with soil containing 10 to 20% petroleum-based oils and organic fluids such as used in transformers and cutting fluids, coolants and the like which contain PCB's. The subject method provides for the removal of a sufficient concentration of PCB's from the soil to provide the soil with a level of PCB's within the guidelines of the Environmental Protection Agency.

  10. Early-onset ocular ochronosis in a girl with alkaptonuria (AKU) and a novel mutation in homogentisate 1,2-dioxygenase (HGD).

    Science.gov (United States)

    Gucev, Z S; Slaveska, N; Laban, N; Danilovski, D; Tasic, V; Pop-Jordanova, N; Zatkova, A

    2011-01-01

    Alkaptonuria (AKU) is a disorder of phenylalanine/tyrosine metabolism due to a defect in the enzyme homogentisate 1,2-dioxygenase (HGD). This recessive disease is caused by mutations in the HGD gene. We report a 14-year-old girl who was referred after presenting black urine. Careful examination revealed ochronosis of the conjunctiva. There was no affection of the cardiac valves. Elevated excretion of homogentisic acid in urine was found. Sequence analysis of the HGD gene from genomic DNA revealed that the patient is a compound heterozygote with a previously described mutation (c.473C>T, p.Pro158Leu), and a novel one (c.821C>T, p.Pro274Leu). Her mother is heterozygous for the novel mutation, while the brother is heterozygous for the previously described mutation. In summary, we describe an alkaptonuric patient with ocular ochronosis and a novel HGD mutation, c.821C>T, p.Pro274Leu.

  11. The evolution of three types of indoleamine 2,3 dioxygenases in fungi with distinct molecular and biochemical characteristics.

    Science.gov (United States)

    Yuasa, Hajime J; Ball, Helen J

    2012-08-01

    Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme and known as a mammalian immunosuppressive molecule. In fungi, the primary role of IDO is to supply nicotinamide adenine dinucleotide (NAD(+)) via the kynurenine pathway. We previously reported that the koji-mold, Aspergillus oryzae has two IDO genes, IDOα and IDOβ. In the present study, we found that A. oryzae also has the third IDO, IDOγ. These three-types of IDOs are widely distributed among the Pezizomycotina fungi, although the black truffle, Tuber melanosporum has only one corresponding gene to IDOα/IDOβ. The yeast, Saccharomyces cerevisiae has a single IDO gene. Generally, Pezizomycotina IDOα showed similar enzymatic properties to the yeast IDO, suggesting that the IDOα is a functional homologue of the S. cerevisiae IDO. In contrast to IDOα, the K(m) value of IDOβ is higher. However, the reaction velocity of IDOβ is very fast, resulting in comparable or higher catalytic efficiency than IDOα. Thus IDOβ may functionally substitute for IDOα in fungal L-Trp metabolism. The enzymatic activity of IDOγ was comparatively very low with the values of enzymatic parameters comparable to vertebrate IDO2 enzymes. IDOα and IDOβ have similar gene structures, suggesting that they were generated by gene duplication which occurred rather early in Pezizomycotina evolution, although the timing of the duplication remains debatable. In contrast, the phylogenetic trees suggest that IDOγs form an evolutionarily distinct group of IDO enzymes, with a closer relationship to group I bacterial IDOs than other fungal IDOs. The ancestor of the IDOγ family is likely to have diverged from other eukaryotic IDOs at a very early stage of eukaryotic evolution. Copyright © 2012. Published by Elsevier B.V.

  12. GenBank blastx search result: AK062096 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062096 001-044-H12 M86348.1 Pseudomonas sp. LB400 biphenyl dioxygenase (bphA), biphenyl dioxygenase (bph...E), biphenyl dioxygenase (bphF) and biphenyl dioxygenase (bphG)s, complete cds, and dihydrodiol dehydrogenase (bphB), partial cds.|BCT BCT 1e-14 +3 ...

  13. Dual Two-Component Regulatory Systems Are Involved in Aromatic Compound Degradation in a Polychlorinated-Biphenyl Degrader, Rhodococcus jostii RHA1 ▿ †

    OpenAIRE

    Takeda, Hisashi; Shimodaira, Jun; Yukawa, Kiyoshi; Hara, Naho; Kasai, Daisuke; Miyauchi, Keisuke; Masai, Eiji; Fukuda, Masao

    2010-01-01

    A Gram-positive polychlorinated-biphenyl (PCB) degrader, Rhodococcus jostii RHA1, degrades PCBs by cometabolism with biphenyl. A two-component BphS1T1 system encoded by bphS1 and bphT1 (formerly bphS and bphT) is responsible for the transcription induction of the five gene clusters, bphAaAbAcAdC1B1, etbAa1Ab1CbphD1, etbAa2Ab2AcD2, etbAdbphB2, and etbD1, which constitute multiple enzyme systems for biphenyl/PCB degradation. The bphS2 and bphT2 genes, which encode BphS2 and BphT2, virtually ide...

  14. Thiol dioxygenase turnover yields benzothiazole products from 2-mercaptoaniline and O2-dependent oxidation of primary alcohols.

    Science.gov (United States)

    Morrow, William P; Sardar, Sinjinee; Thapa, Pawan; Hossain, Mohammad S; Foss, Frank W; Pierce, Brad S

    2017-10-01

    Thiol dioxygenases are non-heme mononuclear iron enzymes that catalyze the O 2 -dependent oxidation of free thiols (-SH) to produce the corresponding sulfinic acid (-SO 2 - ). Previous chemical rescue studies identified a putative Fe III -O 2 - intermediate that precedes substrate oxidation in Mus musculus cysteine dioxygenase (Mm CDO). Given that a similar reactive intermediate has been identified in the extradiol dioxygenase 2, 3-HCPD, it is conceivable that these enzymes share other mechanistic features with regard to substrate oxidation. To explore this possibility, enzymatic reactions with Mm CDO (as well as the bacterial 3-mercaptopropionic acid dioxygenase, Av MDO) were performed using a substrate analogue (2-mercaptoaniline, 2ma). This aromatic thiol closely approximates the catecholic substrate of homoprotocatechuate of 2, 3-HPCD while maintaining the 2-carbon thiol-amine separation preferred by Mm CDO. Remarkably, both enzymes exhibit 2ma-gated O 2 -consumption; however, none of the expected products for thiol dioxygenase or intra/extradiol dioxygenase reactions were observed. Instead, benzothiazoles are produced by the condensation of 2ma with aldehydes formed by an off-pathway oxidation of primary alcohols added to aqueous reactions to solubilize the substrate. The observed oxidation of 1º-alcohols in 2ma-reactions is consistent with the formation of a high-valent intermediate similar to what has been reported for cytochrome P450 and mononuclear iron model complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Low indoleamine 2,3-dioxygenase activity in persistent food allergy in children.

    Science.gov (United States)

    Buyuktiryaki, B; Sahiner, U M; Girgin, G; Birben, E; Soyer, O U; Cavkaytar, O; Cetin, C; Arik Yilmaz, E; Yavuz, S T; Kalayci, O; Baydar, T; Sackesen, C

    2016-02-01

    Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated. Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA. Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and β-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively). Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Spatial gradients of polychlorinated biphenyls (PCBs) and organochlorine pesticides

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Spatial gradients of polychlorinated biphenyls (PCBs) and organochlorine pesticides were examined in the young-of-the-year (YOY) blueÂżsh collected in the vicinity...

  17. Bioaccumulation dynamics of polychlorinated biphenyls (PCBs) and organochlorine pesticides

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Bioaccumulation dynamics of polychlorinated biphenyls (PCBs) and organochlorine pesticides was examined in young-of-the-year bluefish from seven sub-estuaries of New...

  18. Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Munir, Shamaila; Larsen, Stine Kiaer; Iversen, Trine Zeeberg

    2012-01-01

    The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tum...... antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.......The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor...

  19. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

  20. Directed evolution of toluene dioxygenase from Pseudomonas putida for improved selectivity toward cis-indandiol during indene bioconversion.

    Science.gov (United States)

    Zhang, N; Stewart, B G; Moore, J C; Greasham, R L; Robinson, D K; Buckland, B C; Lee, C

    2000-10-01

    Toluene dioxygenase (TDO) from Pseudomonas putida F1 converts indene to a mixture of cis-indandiol (racemic), 1-indenol, and 1-indanone. The desired product, cis-(1S,2R)-indandiol, is a potential key intermediate in the chemical synthesis of indinavir sulfate (Crixivan), Merck's HIV-1 protease inhibitor for the treatment of AIDS. To reduce the undesirable byproducts 1-indenol and 1-indanone formed during indene bioconversion, the recombinant TDO expressed in Escherichia coli was evolved by directed evolution using the error-prone polymerase chain reaction (epPCR) method. High-throughput fluorometric and spectrophotometric assays were developed for rapid screening of the mutant libraries in a 96-well format. Mutants with reduced 1-indenol by-product formation were identified, and the individual indene bioconversion product profiles of the selected mutants were confirmed by HPLC. Changes in the amino acid sequence of the mutant enzymes were identified by analyzing the nucleotide sequence of the genes. A mutant with the most desirable product profile from each library, defined as the most reduced 1-indenol concentration and with the highest cis-(1S,2R)-indandiol enantiomeric excess, was used to perform each subsequent round of mutagenesis. After three rounds of mutagenesis and screening, mutant 1C4-3G was identified to have a threefold reduction in 1-indenol formation over the wild type (20% vs 60% of total products) and a 40% increase of product (cis-indandiol) yield.

  1. Dioxygenases Catalyze O-Demethylation and O,O-Demethylenation with Widespread Roles in Benzylisoquinoline Alkaloid Metabolism in Opium Poppy*

    Science.gov (United States)

    Farrow, Scott C.; Facchini, Peter J.

    2013-01-01

    In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy. PMID:23928311

  2. Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy.

    Science.gov (United States)

    Farrow, Scott C; Facchini, Peter J

    2013-10-04

    In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy.

  3. Eucalyptus ESTs involved in the production of 9-cis epoxycarotenoid dioxygenase, a regulatory enzyme of abscisic acid production

    Directory of Open Access Journals (Sweden)

    Iraê A. Guerrini

    2005-01-01

    Full Text Available Abscisic acid (ABA regulates stress responses in plants, and genomic tools can help us to understand the mechanisms involved in that process. FAPESP, a Brazilian research foundation, in association with four private forestry companies, has established the FORESTs database (https://forests.esalq.usp.br. A search was carried out in the Eucalyptus expressed sequence tag database to find ESTs involved with 9-cis epoxycarotenoid dioxygenase (NCED, the regulatory enzyme for ABA biosynthesis, using the basic local BLAST alignment tool. We found four clusters (EGEZLV2206B11.g, EGJMWD2252H08.g, EGBFRT3107F10.g, and EGEQFB1200H10.g, which represent similar sequences of the gene that produces NCED. Data showed that the EGBFRT3107F10.g cluster was similar to the maize (Zea mays NCED enzyme, while EGEZLV2206B11.g and EGJMWD2252H08.g clusters were similar to the avocado (Persea americana NCED enzyme. All Eucalyptus clusters were expressed in several tissues, especially in flower buds, where ABA has a special participation during the floral development process.

  4. Whole-Cell Fluorescent Biosensors for Bioavailability and Biodegradation of Polychlorinated Biphenyls

    Directory of Open Access Journals (Sweden)

    David Ryan

    2010-02-01

    Full Text Available Whole-cell microbial biosensors are one of the newest molecular tools used in environmental monitoring. Such biosensors are constructed through fusing a reporter gene such as lux, gfp or lacZ,to a responsive promoter. There have been many reports of the applications of biosensors, particularly their use in assaying pollutant toxicity and bioavailability. This paper reviews the basic concepts behind the construction of whole-cell microbial biosensors for pollutant monitoring, and describes the applications of two such biosensors for detecting the bioavailability and biodegradation of Polychlorinated Biphenyls (PCBs.

  5. Substrate and pH-Dependent Kinetic Profile of 3-Mercaptopropionate Dioxygenase from Pseudomonas aeruginosa.

    Science.gov (United States)

    Fellner, Matthias; Aloi, Sekotilani; Tchesnokov, Egor P; Wilbanks, Sigurd M; Jameson, Guy N L

    2016-03-08

    Thiol dioxygenases catalyze the synthesis of sulfinic acids in a range of organisms from bacteria to mammals. A thiol dioxygenase from the bacterium Pseudomonas aeruginosa oxidizes both 3-mercaptopropionic acid and cysteine, with a ∼70 fold preference for 3-mercaptopropionic acid over all pHs. This substrate reactivity is widened compared to other thiol dioxygenases and was exploited in this investigation of the residues important for activity. A simple model incorporating two protonation events was used to fit profiles of the Michaelis-Menten parameters determined at different pH values for both substrates. The pKs determined using plots of k(cat)/Km differ at low pH, but not in a way easily attributable to protonation of the substrate alone and share a common value at higher pH. Plots of k(cat) versus pH are also quite different at low pH showing the monoprotonated ES complexes with 3-mercaptopropionic acid and cysteine have different pKs. At higher pH, k(cat) decreases sigmoidally with a similar pK regardless of substrate. Loss of reactivity at high pH is attributed to deprotonation of tyrosine 159 and its influence on dioxygen binding. A mechanism is proposed by which deprotonation of tyrosine 159 both blocks oxygen binding and concomitantly promotes cystine formation. Finally, the role of tyrosine 159 was further probed by production of a G95C variant that is able to form a cysteine-tyrosine crosslink homologous to that found in mammalian cysteine dioxygenases. Activity of this variant is severely impaired. Crystallography shows that when un-crosslinked, the cysteine thiol excludes tyrosine 159 from its native position, while kinetic analysis shows that the thioether bond impairs reactivity of the crosslinked form.

  6. An isoelectronic NO dioxygenase reaction using a nonheme iron(III)-peroxo complex and nitrosonium ion.

    Science.gov (United States)

    Yokoyama, Atsutoshi; Han, Jung Eun; Karlin, Kenneth D; Nam, Wonwoo

    2014-02-18

    Reaction of a nonheme iron(III)-peroxo complex, [Fe(III)(14-TMC)(O2)](+), with NO(+), a transformation which is essentially isoelectronic with that for nitric oxide dioxygenases [Fe(III)(O2˙(-)) + NO], affords an iron(IV)-oxo complex, [Fe(IV)(14-TMC)(O)](2+), and nitrogen dioxide (NO2), followed by conversion to an iron(III)-nitrato complex, [Fe(III)(14-TMC)(NO3)(F)](+).

  7. An isoelectronic NO dioxygenase reaction using a nonheme iron(III)-peroxo complex and nitrosonium ion†

    Science.gov (United States)

    Yokoyama, Atsutoshi; Han, Jung Eun; Karlin, Kenneth D.; Nam, Wonwoo

    2014-01-01

    Reaction of a nonheme iron(III)-peroxo complex, [FeIII(14-TMC)(O2)]+, with NO+, a transformation which is essentially isoelectronic with that for nitric oxide dioxygenases [Fe(III)(O2•−) + NO], affords an iron(IV)-oxo complex, [FeIV(14-TMC)(O)]2+, and nitrogen dioxide (NO2), followed by conversion to an iron(III)-nitrato complex, [FeIII(14-TMC)(NO3)(F)]+. PMID:24394960

  8. An isoelectronic NO dioxygenase reaction using a nonheme iron(III)-peroxo complex and nitrosonium ion†

    OpenAIRE

    Yokoyama, Atsutoshi; Han, Jung Eun; Karlin, Kenneth D.; Nam, Wonwoo

    2014-01-01

    Reaction of a nonheme iron(III)-peroxo complex, [FeIII(14-TMC)(O2)]+, with NO+, a transformation which is essentially isoelectronic with that for nitric oxide dioxygenases [Fe(III)(O2•−) + NO], affords an iron(IV)-oxo complex, [FeIV(14-TMC)(O)]2+, and nitrogen dioxide (NO2), followed by conversion to an iron(III)-nitrato complex, [FeIII(14-TMC)(NO3)(F)]+.

  9. Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis

    KAUST Repository

    Frusciante, Sarah; Diretto, Gianfranco; Bruno, Mark; Ferrante, Paola; Pietrella, Marco; Prado-Cabrero, Alfonso; Rubio-Moraga, Á ngela L.; Beyer, Peter D.; Gó mez-Gó mez, Lourdes; Al-Babili, Salim; Giuliano, Giovanni

    2014-01-01

    Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7′,8′ double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8′-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8′-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.

  10. Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis

    KAUST Repository

    Frusciante, Sarah

    2014-08-05

    Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7′,8′ double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8′-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8′-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.

  11. Isolation and characterization of two novel halotolerant Catechol 2, 3-dioxygenases from a halophilic bacterial consortium

    Science.gov (United States)

    Guo, Guang; Fang, Tingting; Wang, Chongyang; Huang, Yong; Tian, Fang; Cui, Qijia; Wang, Hui

    2015-12-01

    Study of enzymes in halophiles will help to understand the mechanism of aromatic hydrocarbons degradation in saline environment. In this study, two novel catechol 2,3-dioxygenases (C23O1 and C23O2) were cloned and overexpressed from a halophilic bacterial consortium enriched from an oil-contaminated saline soil. Phylogenetic analysis indicated that the novel C23Os and their relatives formed a new branch in subfamily I.2.A of extradiol dioxygenases and the sequence differences were further analyzed by amino acid sequence alignment. Two enzymes with the halotolerant feature were active over a range of 0-30% salinity and they performed more stable at high salinity than in the absence of salt. Surface electrostatic potential and amino acids composition calculation suggested high acidic residues content, accounting for their tolerance to high salinity. Moreover, two enzymes were further characterized. The enzymes activity both increased in the presence of Fe3+, Fe2+, Cu2+ and Al3+ and showed no significant inhibition by other tested metal ions. The optimal temperatures for the C23Os were 40 °C and 60 °C and their best substrates were catechol and 4-methylcatechol respectively. As the firstly isolated and characterized catechol dioxygenases from halophiles, the two halotolerant C23Os presented novel characteristics suggesting their potential application in aromatic hydrocarbons biodegradation.

  12. Molecular cloning and characterization of cDNAs encoding carotenoid cleavage dioxygenase in bitter melon (Momordica charantia).

    Science.gov (United States)

    Tuan, Pham Anh; Park, Sang Un

    2013-01-01

    Carotenoid cleavage dioxygenases (CCDs) are a family of enzymes that catalyze the oxidative cleavage of carotenoids at various chain positions to form a broad spectrum of apocarotenoids, including aromatic substances, pigments and phytohormones. Using the rapid amplification of cDNA ends (RACE) PCR method, we isolated three cDNA-encoding CCDs (McCCD1, McCCD4, and McNCED) from Momordica charantia. Amino acid sequence alignments showed that they share high sequence identity with other orthologous genes. Quantitative real-time RT PCR (reverse transcriptase PCR) analysis revealed that the expression of McCCD1 and McCCD4 was highest in flowers, and lowest in roots and old leaves (O-leaves). During fruit maturation, the two genes displayed differential expression, with McCCD1 peaking at mid-stage maturation while McCCD4 showed the lowest expression at that stage. The mRNA expression level of McNCED, a key enzyme involved in abscisic acid (ABA) biosynthesis, was high during fruit maturation and further increased at the beginning of seed germination. When first-leaf stage plants of M. charantia were exposed to dehydration stress, McNCED mRNA expression was induced primarily in the leaves and, to a lesser extend, in roots and stems. McNCED expression was also induced by high temperature and salinity, while treatment with exogenous ABA led to a decrease. These results should be helpful in determining the substrates and cleavage sites catalyzed by CCD genes in M. charantia, and also in defining the roles of CCDs in growth and development, and in the plant's response to environmental stress. Copyright © 2012 Elsevier GmbH. All rights reserved.

  13. Anaerobic degradation of Polychlorinated Biphenyls (PCBs) and Polychlorinated Biphenyls Ethers (PBDEs), and microbial community dynamics of electronic waste-contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Song, Mengke [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Luo, Chunling, E-mail: clluo@gig.ac.cn [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Li, Fangbai [Guangdong Institute of Eco-environmental and Soil Sciences, Guangzhou 510650 (China); Jiang, Longfei [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); College of Life Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Wang, Yan [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Zhang, Dayi [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom); Zhang, Gan [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China)

    2015-01-01

    Environmental contamination caused by electronic waste (e-waste) recycling is attracting increasing attention worldwide because of the threats posed to ecosystems and human safety. In the present study, we investigated the feasibility of in situ bioremediation of e-waste-contaminated soils. We found that, in the presence of lactate as an electron donor, higher halogenated congeners were converted to lower congeners via anaerobic halorespiration using ferrous ions in contaminated soil. The 16S rRNA gene sequences of terminal restriction fragments indicated that the three dominant strains were closely related to known dissimilatory iron-reducing bacteria (DIRB) and those able to perform dehalogenation upon respiration. The functional species performed the activities of ferrous oxidation to ferric ions and further ferrous reduction for dehalogenation. The present study links iron cycling to degradation of halogenated materials in natural e-waste-contaminated soil, and highlights the synergistic roles of soil bacteria and ferrous/ferric ion cycling in the dehalogenation of polychlorinated biphenyls (PCBs) and polybrominated biphenyl ethers (PBDEs). - Highlights: • The biodegradation PCBs and PBDEs in e-waste contaminated soils was studied. • DIRB and arylhalorespiring bacteria were responsive to dehalogenation respiration. • Soil bacteria and Fe ion cycling play synergistic roles in dehalogenation.

  14. Consolidated PCBs [polychlorinated biphenyls] improves waste control

    International Nuclear Information System (INIS)

    Smith, E.

    1991-01-01

    Consolidation of polychlorinated biphenyl (PCB) wastes is recommended for improving ownership control of wastes, eliminating PCB storage sites, and increasing cost-effectiveness of waste management. In Ontario, sites receiving the waste must be owned by the waste generator and registered as a PCB site. All PCBs must be removed from a site with no contaminated materials or wastes left behind, which requires a thorough site assessment to identify wastes prior to removal, a sampling and analytical scheme if necessary, and an approved plan for site cleanup. If large volumes of PCB-contaminated oil are involved, it may be cost-effective to put oil from several sites into bulk tanks and thus avoid the need to handle and decontaminate a large number of drums. With low volumes of oil, it may be possible to move the waste to another site where mobile PCB destruction is taking place. It also may be possible to get approval to blend high-level PCB liquids with mineral oil to reduce the PCB concentration to a level where chemical decontamination is allowed. For large volumes of high-level PCB wastes, consolidation will be necessary simply because of the high costs of mobilizing an incinerator and the requirement for public hearings for each incineration project. To make such a project cost-effective, PCB wastes will have to be concentrated from a large geographic area. 1 fig

  15. New technologies for PCB [polychlorinated biphenyl] decontamination

    International Nuclear Information System (INIS)

    Webber, I.

    1993-01-01

    Polychlorinated biphenyls (PCB) were mixed with chlorobenzenes to reduce viscosity and provide for both electrical insulation and convective heat transfers. These mixtures were known as askarels, and ca 99.8% of PCBs used in electrical applications are contained in askarel-filled transformers and capacitors. It is estimated that there are ca 180 million gal of PCB-contaminated oil distributed through over 3 million transformers in the USA. Technology used for decontaminating these transformers depends on the concentration of the PCB contamination. At low PCB concentrations of up to ca 2,000 ppM, chemical methods can be used; at higher concentrations, alternative disposal options become more attractive. For chemical treatment, a small mobile unit using quick-reacting reagents has been developed for on-site decontamination. For highly contaminated transformers, retrofilling is very attractive since the owner's liability is minimized at minimum cost. Conventional flush/drain procedures have such drawbacks as the inability to remove oil trapped in windings and the leaching of trapped PCBs back into the uncontaminated retrofill oil over time. A new process has been developed to solve the leaching problem and to decontaminate the drained askarel at room temperature using a catalyst. An alternative disposal strategy involves dismantling the transformer carcass, incinerating non-recyclable materials, and cleaning the metals and wire with solvent. 8 figs

  16. Biphenyl Modulates the Expression and Function of Respiratory Oxidases in the Polychlorinated-Biphenyls Degrader Pseudomonas pseudoalcaligenes KF707

    Directory of Open Access Journals (Sweden)

    Federica Sandri

    2017-06-01

    Full Text Available Pseudomonas pseudoalcaligenes KF707 is a soil bacterium which is known for its capacity to aerobically degrade harmful organic compounds such as polychlorinated biphenyls (PCBs using biphenyl as co-metabolite. Here we provide the first genetic and functional analysis of the KF707 respiratory terminal oxidases in cells grown with two different carbon sources: glucose and biphenyl. We identified five terminal oxidases in KF707: two c(caa3 type oxidases (Caa3 and Ccaa3, two cbb3 type oxidases (Cbb31 and Cbb32, and one bd type cyanide-insensitive quinol oxidase (CIO. While the activity and expression of both Cbb31 and Cbb32 oxidases was prevalent in glucose grown cells as compared to the other oxidases, the activity and expression of the Caa3 oxidase increased considerably only when biphenyl was used as carbon source in contrast to the Cbb32 oxidase which was repressed. Further, the respiratory activity and expression of CIO was up-regulated in a Cbb31 deletion strain as compared to W.T. whereas the CIO up-regulation was not present in Cbb32 and C(caa3 deletion mutants. These results, together, reveal that both function and expression of cbb3 and caa3 type oxidases in KF707 are modulated by biphenyl which is the co-metabolite needed for the activation of the PCBs-degradation pathway.

  17. OXIDATION OF POLYCHLORINATED BIPHENYLS BY PSEUDOMONAS SP. STRAIN LB400 AND PSEUDOMONAS PSEUDOALCALIGENES KF707

    Science.gov (United States)

    Biphenyl-grown cells and cell extracts prepared from biphenyl-grown cells of Pseudomonas sp. strain LB400 oxidize a much wider range of chlorinated biphenyls than do analogous preparations from Pseudomonas pseudoalcaligenes KF707. These results are attributed to differences in th...

  18. Exposure Monitoring and Risk Assessment of Biphenyl in the Workplace

    Directory of Open Access Journals (Sweden)

    Hyeon-Yeong Kim

    2015-05-01

    Full Text Available This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m3, respectively. In addition, the carcinogenic risk of biphenyl as determined by risk assessment was 0.14 × 10−4 (central tendency exposure and 0.56 × 10−4 (reasonable maximum exposure, which is below the acceptable risk value of 1.0 × 10−4. Furthermore, the central tendency exposure and reasonable maximum exposure hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively, which are all lower than the acceptable hazard quotient of 1.0. Therefore, exposure to biphenyl was found to be safe in current workplace environments. Because occupational exposure limits are based on socioeconomic assessment, they are generally higher than true values seen in toxicity experiments. Based on the results of exposure monitoring of biphenyl, the current occupational exposure limits in Korea could be reviewed.

  19. Exposure monitoring and risk assessment of biphenyl in the workplace.

    Science.gov (United States)

    Kim, Hyeon-Yeong; Shin, Sae-Mi; Ham, Miran; Lim, Cheol-Hong; Byeon, Sang-Hoon

    2015-05-13

    This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m³, respectively. In addition, the carcinogenic risk of biphenyl as determined by risk assessment was 0.14 × 10⁻⁴ (central tendency exposure) and 0.56 × 10⁻⁴ (reasonable maximum exposure), which is below the acceptable risk value of 1.0 × 10⁻⁴. Furthermore, the central tendency exposure and reasonable maximum exposure hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively, which are all lower than the acceptable hazard quotient of 1.0. Therefore, exposure to biphenyl was found to be safe in current workplace environments. Because occupational exposure limits are based on socioeconomic assessment, they are generally higher than true values seen in toxicity experiments. Based on the results of exposure monitoring of biphenyl, the current occupational exposure limits in Korea could be reviewed.

  20. Structure of the 2, 4′-dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP

    Energy Technology Data Exchange (ETDEWEB)

    Keegan, R.; Lebedev, A. [RAL, Harwell Oxford, Didcot OX11 0FA (United Kingdom); Erskine, P.; Guo, J.; Wood, S. P. [UCL Division of Medicine (Royal Free Campus), Rowland Hill Street, London NW3 2PF (United Kingdom); Hopper, D. J. [Aberystwyth University, Penglais, Aberystwyth SY23 3DA Wales (United Kingdom); Rigby, S. E. J. [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Cooper, J. B., E-mail: jon.cooper@ucl.ac.uk [UCL Division of Medicine (Royal Free Campus), Rowland Hill Street, London NW3 2PF (United Kingdom); RAL, Harwell Oxford, Didcot OX11 0FA (United Kingdom)

    2014-09-01

    The first X-ray structure of a 2, 4′-dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP at a resolution of 2.2 Å is reported. This structure establishes that the enzyme adopts the cupin-fold, forming compact dimers with a pronounced hydrophobic interface between the monomers. Each monomer possesses a catalytic ferrous iron that is coordinated by three histidines (76, 78 and 114) and an additional ligand which has been putatively assigned as a carbonate, although formate and acetate are possibilities. The enzyme 2, 4′-dihydroxyacetophenone dioxygenase (DAD) catalyses the conversion of 2, 4′-dihydroxyacetophenone to 4-hydroxybenzoic acid and formic acid with the incorporation of molecular oxygen. Whilst the vast majority of dioxygenases cleave within the aromatic ring of the substrate, DAD is very unusual in that it is involved in C—C bond cleavage in a substituent of the aromatic ring. There is evidence that the enzyme is a homotetramer of 20.3 kDa subunits, each containing nonhaem iron, and its sequence suggests that it belongs to the cupin family of dioxygenases. In this paper, the first X-ray structure of a DAD enzyme from the Gram-negative bacterium Alcaligenes sp. 4HAP is reported, at a resolution of 2.2 Å. The structure establishes that the enzyme adopts a cupin fold, forming dimers with a pronounced hydrophobic interface between the monomers. The catalytic iron is coordinated by three histidine residues (76, 78 and 114) within a buried active-site cavity. The iron also appears to be tightly coordinated by an additional ligand which was putatively assigned as a carbonate dianion since this fits the electron density optimally, although it might also be the product formate. The modelled carbonate is located in a position which is highly likely to be occupied by the α-hydroxyketone group of the bound substrate during catalysis. Modelling of a substrate molecule in this position indicates that it will interact with many conserved amino acids in

  1. Involvement of the Cys-Tyr cofactor on iron binding in the active site of human cysteine dioxygenase.

    Science.gov (United States)

    Arjune, Sita; Schwarz, Guenter; Belaidi, Abdel A

    2015-01-01

    Sulfur metabolism has gained increasing medical interest over the last years. In particular, cysteine dioxygenase (CDO) has been recognized as a potential marker in oncology due to its altered gene expression in various cancer types. Human CDO is a non-heme iron-dependent enzyme, which catalyzes the irreversible oxidation of cysteine to cysteine sulfinic acid, which is further metabolized to taurine or pyruvate and sulfate. Several studies have reported a unique post-translational modification of human CDO consisting of a cross-link between cysteine 93 and tyrosine 157 (Cys-Tyr), which increases catalytic efficiency in a substrate-dependent manner. However, the reaction mechanism by which the Cys-Tyr cofactor increases catalytic efficiency remains unclear. In this study, steady-state kinetics were determined for wild type CDO and two different variants being either impaired or saturated with the Cys-Tyr cofactor. Cofactor formation in CDO resulted in an approximately fivefold increase in k cat and tenfold increase in k cat/K m over the cofactor-free CDO variant. Furthermore, iron titration experiments revealed an 18-fold decrease in K d of iron upon cross-link formation. This finding suggests a structural role of the Cys-Tyr cofactor in coordinating the ferrous iron in the active site of CDO in accordance with the previously postulated reaction mechanism of human CDO. Finally, we identified product-based inhibition and α-ketoglutarate and glutarate as CDO inhibitors using a simplified well plate-based activity assay. This assay can be used for high-throughput identification of additional inhibitors, which may contribute to understand the functional importance of CDO in sulfur amino acid metabolism and related diseases.

  2. Dioxygenase-encoding AtDAO1 gene controls IAA oxidation and homeostasis in Arabidopsis

    Czech Academy of Sciences Publication Activity Database

    Porco, S.; Pěnčík, Aleš; Rashed, A.; Voss, U.; Casanova-Saez, R.; Bishopp, A.; Golebiowska, A.; Bhosale, R.; Swarup, R.; Swarup, K.; Peňáková, Pavlína; Novák, Ondřej; Staswick, P.; Hedden, P.; Phillips, A.; Vissenberg, K.; Bennett, M.J.

    2016-01-01

    Roč. 113, č. 39 (2016), s. 11016-11021 ISSN 0027-8424 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Arabidopsis thaliana * IAA degradation * oxidase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.661, year: 2016

  3. Expression of 9-cis-EPOXYCAROTENOID DIOXYGENASE4 Is Essential for Thermoinhibition of Lettuce Seed Germination but Not for Seed Development or Stress Tolerance[C][W

    Science.gov (United States)

    Huo, Heqiang; Dahal, Peetambar; Kunusoth, Keshavulu; McCallum, Claire M.; Bradford, Kent J.

    2013-01-01

    Thermoinhibition, or failure of seeds to germinate at warm temperatures, is common in lettuce (Lactuca sativa) cultivars. Using a recombinant inbred line population developed from a lettuce cultivar (Salinas) and thermotolerant Lactuca serriola accession UC96US23 (UC), we previously mapped a quantitative trait locus associated with thermoinhibition of germination to a genomic region containing a gene encoding a key regulated enzyme in abscisic acid (ABA) biosynthesis, 9-cis-EPOXYCAROTENOID DIOXYGENASE4 (NCED4). NCED4 from either Salinas or UC complements seeds of the Arabidopsis thaliana nced6-1 nced9-1 double mutant by restoring germination thermosensitivity, indicating that both NCED4 genes encode functional proteins. Transgenic expression of Salinas NCED4 in UC seeds resulted in thermoinhibition, whereas silencing of NCED4 in Salinas seeds led to loss of thermoinhibition. Mutations in NCED4 also alleviated thermoinhibition. NCED4 expression was elevated during late seed development but was not required for seed maturation. Heat but not water stress elevated NCED4 expression in leaves, while NCED2 and NCED3 exhibited the opposite responses. Silencing of NCED4 altered the expression of genes involved in ABA, gibberellin, and ethylene biosynthesis and signaling pathways. Together, these data demonstrate that NCED4 expression is required for thermoinhibition of lettuce seeds and that it may play additional roles in plant responses to elevated temperature. PMID:23503626

  4. Fused Heterocyclic Compounds as Potent Indoleamine-2,3-dioxygenase 1 Inhibitors.

    Science.gov (United States)

    Panda, Subhankar; Roy, Ashalata; Deka, Suman Jyoti; Trivedi, Vishal; Manna, Debasis

    2016-12-08

    Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives. Further lead optimizations directed to the identification of potent compounds, 4j and 4l (IC 50 = 260 and 151 nM, respectively). These compounds also exhibited IDO1 inhibitory activities in the low nanomolar range in MDA-MB-231 cells with very low cytotoxicity. Stronger selectivity for the IDO1 enzyme (>300-fold) over tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. Hence, these fused heterocyclic compounds are attractive candidates for the advanced study of IDO1-dependent cellular function and immunotherapeutic applications.

  5. Polychlorinated biphenyl sources, environmental levels, and exposures in school buildings

    Science.gov (United States)

    Background: Building materials and components containing polychlorinated biphenyls (PCBs) were used in some U.S. school buildings until the late 1970s and may be present today. There is limited information on source factors and occupant exposures. Methods: Analysis of PCBs in mat...

  6. Congener profiles of polychlorinated biphenyls and the effect on ...

    African Journals Online (AJOL)

    This study investigated the effect of freshwater as a point source of PCBs contributing to a marine outfall region. Inflowing and outflowing water from the North End Lake, Port Elizabeth, was collected to determine the contamination levels of polychlorinated biphenyls (PCBs). Mussels at the outflow to the sea were also ...

  7. Metabolic Pathways of Polychlorinated Biphenyls Degradation by Pseudomonas sp. 2

    Czech Academy of Sciences Publication Activity Database

    Komancová, M.; Jurčová, Irena; Kochánková, L.; Burkhard, J.

    2003-01-01

    Roč. 50, č. 4 (2003), s. 537ů543 ISSN 0045-6535 Institutional research plan: CEZ:AV0Z4072921 Keywords : polychlorinated biphenyls * biodegradation * aerobic bacteria Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.904, year: 2003

  8. Polychlorinated biphenyl exposure and deiodinase activity in young infants

    NARCIS (Netherlands)

    Soechitram, Shalini D.; Berghuis, Sietske A.; Visser, Theo J.; Sauer, Pieter J. J.

    2017-01-01

    Background: Several studies have shown effects of polychlorinated biphenyls (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while other studies did not find such effects. How PCBs might affect thyroid hormone metabolism, is still unclear. Potential mechanisms are direct

  9. Attenuation of polychlorinated biphenyl sorption to charcoal by humic acids

    NARCIS (Netherlands)

    Koelmans, A.A.; Meulman, B.; Meijer, T.; Jonker, M.T.O.

    2009-01-01

    Strong sorption to black carbon may limit the environmental risks of organic pollutants, but interactions with cosorbing humic acid (HA) may interfere. We studied the attenuative effect of HA additions on the sorption of polychlorinated biphenyls (PCBs) to a charcoal. "Intrinsic" sorption to

  10. Polychlorinated Biphenyls: In situ Bioremediation from the Environment

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) are a group of hydrophobic and stable organic compounds consisting of 209 possible congeners. Because of their unique physico-chemical properties, PCBs were used in a wide range of industrial applications. The properties that made PCBs useful in i...

  11. Photochemical of Polychlorinated biphenyl by the photolysis and ...

    African Journals Online (AJOL)

    pressure mercury lamp. The whole Lamp was immersed in a reactor thermostat controlling the temperature at 32 ± 2 °C. The Polychlorinated biphenyls (PCBs) were analyzed by GC/ECD. The degradation of PCBs in terms of one, two and three lamp ...

  12. The role of adrenal hormones in the activation of tryptophan 2,3-dioxygenase by nicotinic acid in rat liver.

    Science.gov (United States)

    Sainio, E L

    1997-09-01

    In this study, our previous finding that nicotinic acid activates tryptophan 2,3-dioxygenase as strongly as tryptophan was investigated in further detail. This study focused on the role of the adrenals in the activation process. Adrenalectomy abolished the activation due to nicotinic acid, but not the activation caused by tryptophan. The role of corticoids and/or adrenomedullary hormones in the enzyme activation was studied, by supplementing these hormones in adrenalectomized rats using minipumps implanted under the skin. The results showed that the enhanced activity of tryptophan 2,3-dioxygenase caused by nicotinic acid was partly restored by adrenaline following adrenalectomy but not by corticosterone supplementation. The results were supported by further experiments in which the rats were treated with adrenaline or corticosterone intraperitoneally before nicotinic acid administration. The conclusion that adrenaline participates in the regulation of tryptophan 2,3-dioxygenase should promote further study to determine whether adrenaline is a general modulator of this enzyme. This experimental model generated new information on the activation mechanism of tryptophan 2,3-dioxygenase by nicotinic acid.

  13. Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model

    NARCIS (Netherlands)

    Taher, Yousef A.; Piavaux, Benoit J. A.; Gras, Renee; van Esch, Betty C. A. M.; Hofman, Gerard A.; Bloksma, Nanne; Henricks, Paul A. J.; van Oosterhout, Antoon J. M.

    Background: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. Objective: We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive

  14. Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production

    NARCIS (Netherlands)

    Metghalchi, Sarvenaz; Ponnuswamy, Padmapriya; Simon, Tabassome; Haddad, Yacine; Laurans, Ludivine; Clement, Marc; Dalloz, Marion; Romain, Melissa; Esposito, Bruno; Koropoulis, Vincent; Lamas, Bruno; Paul, Jean-Louis; Cottin, Yves; Kotti, Salma; Bruneval, Patrick; Callebert, Jacques; den Ruijter, Hester; Launay, Jean-Marie; Danchin, Nicolas; Sokol, Harry; Tedgui, Alain; Taleb, Soraya; Mallat, Ziad

    2015-01-01

    Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme that catalizes the degradation of tryptophan along the kynurenine pathway. Here, we show that Ido1 activity sustains an immunostimulatory potential through inhibition of interleukin (Il)10. In atherosclerosis, Ido1-dependent inhibition

  15. Cloning of two individual cDNAS encoding 9-cis-epoxycarotenoid dioxygenase from Gentiana lutea, their tissue-specific expression and physiological effect in transgenic tobacco.

    Science.gov (United States)

    Zhu, Changfu; Kauder, Friedrich; Römer, Susanne; Sandmann, Gerhard

    2007-02-01

    Two 9-cis-epoxycarotenoid dioxygenase (NCED) cDNAs have been cloned from a petal library of Gentiana lutea. Both cDNAs carry a putative transit sequence for chloroplast import and differ mainly in their length and the 5'-flanking regions. GlNCED1 was evolutionary closely related to Arabidopsis thaliana NCED6 whereas GlNCED2 showed highest homology to tomato NCED1 and A. thaliana NCED3. The amounts of GlNCED2 transcript were below Northern detection in G. lutea. In contrast, GlNCED1 was specifically expressed at higher levels in developing flowers when petals start appearing. By genetic engineering of tobacco with coding regions of either gene under a constitutive promoter, their function was further analyzed. Although mRNA of both genes was detectable in the corresponding transgenic plants, a physiological effect was only found for GlNCED1 but not for GlNCED2. In germination experiments of GlNCED1 transgenic lines, delayed radicle formation and cotyledon appearance were observed. However, the transformants exhibited no improved tolerance against desiccation stress. In contrast to other plants with over-expressed NCEDs, prolonged delay of seed germination is the only abscisic-acid-related phenotypic effect in the GlNCED1 transgenic lines.

  16. Targeting the immunoregulatory indoleamine 2,3 dioxygenase pathway in immunotherapy

    Science.gov (United States)

    Johnson, Burles A; Baban, Babak; Mellor, Andrew L

    2009-01-01

    Natural immune tolerance is a formidable barrier to successful immunotherapy to treat established cancers and chronic infections. Conversely, creating robust immune tolerance via immunotherapy is the major goal in treating autoimmune and allergic diseases, and enhancing survival of transplanted organs and tissues. In this review, we focus on a natural mechanism that creates local T-cell tolerance in many clinically relevant settings of chronic inflammation involving expression of the cytosolic enzyme indoleamine 2,3-dioxygenase (IDO) by specialized subsets of dendritic cells. IDO-expressing dendritic cells suppress antigen-specific T-cell responses directly, and induce bystander suppression by activating regulatory T cells. Thus, manipulating IDO is a promising strategy to treat a range of chronic inflammatory diseases. PMID:20161103

  17. The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels

    2009-01-01

    BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance...... to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T...... of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals...

  18. Probing the structural basis of oxygen binding in a cofactor-independent dioxygenase.

    Science.gov (United States)

    Li, Kunhua; Fielding, Elisha N; Condurso, Heather L; Bruner, Steven D

    2017-07-01

    The enzyme DpgC is included in the small family of cofactor-independent dioxygenases. The chemistry of DpgC is uncommon as the protein binds and utilizes dioxygen without the aid of a metal or organic cofactor. Previous structural and biochemical studies identified the substrate-binding mode and the components of the active site that are important in the catalytic mechanism. In addition, the results delineated a putative binding pocket and migration pathway for the co-substrate dioxygen. Here, structural biology is utilized, along with site-directed mutagenesis, to probe the assigned dioxygen-binding pocket. The key residues implicated in dioxygen trafficking were studied to probe the process of binding, activation and chemistry. The results support the proposed chemistry and provide insight into the general mechanism of dioxygen binding and activation.

  19. Molecular dynamics simulations and free energy calculations on the enzyme 4-hydroxyphenylpyruvate dioxygenase.

    Science.gov (United States)

    De Beer, Stephanie B A; Glättli, Alice; Hutzler, Johannes; Vermeulen, Nico P E; Oostenbrink, Chris

    2011-07-30

    4-Hydroxyphenylpyruvate dioxygenase is a relevant target in both pharmaceutical and agricultural research. We report on molecular dynamics simulations and free energy calculations on this enzyme, in complex with 12 inhibitors for which experimental affinities were determined. We applied the thermodynamic integration approach and the more efficient one-step perturbation. Even though simulations seem well converged and both methods show excellent agreement between them, the correlation with the experimental values remains poor. We investigate the effect of slight modifications on the charge distribution of these highly conjugated systems and find that accurate models can be obtained when using improved force field parameters. This study gives insight into the applicability of free energy methods and current limitations in force field parameterization. Copyright © 2011 Wiley Periodicals, Inc.

  20. Role of inhalation in exposure to polychlorinated biphenyls (PCBs)

    International Nuclear Information System (INIS)

    Monarca, S.; Dominici, L.; Fatigoni, C.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are a group of aromatic compounds consisting of a biphenyl variously chlorinated. Industrial production of PCBs started in 1929 and stopped in the second half of the '70s in USA and in the late 80's and 90's in Europe. PCBs are ubiquitous pollutants. The way of human exposure to PCBs is a matter of discussion. Scientific data show that the greater exposure occurs through diet. However, other available data suggest a not marginal role of the inhalation exposure. The sources of PCBs to which population are exposed depend on the amount of redistribution of these compounds released in the environment. The aim of this work is to highlight numerous studies proving that the intake of PCBs by inhalation cannot be neglected, in particular in heavily industrialized areas and where the concentration of PCBs in the environmental matrices is particularly high

  1. Anaerobic Dehalogenation of Hydroxylated Polychlorinated Biphenyls by Desulfitobacterium dehalogenans

    OpenAIRE

    Wiegel, Juergen; Zhang, Xiaoming; Wu, Qingzhong

    1999-01-01

    Ten years after reports on the existence of anaerobic dehalogenation of polychlorinated biphenyls (PCBs) in sediment slurries, we report here on the rapid reductive dehalogenation of para-hydroxylated PCBs (HO-PCBs), the excreted main metabolites of PCB in mammals, which can exhibit estrogenic and antiestrogenic activities in humans. The anaerobic bacterium Desulfitobacterium dehalogenans completely dehalogenates all flanking chlorines (chlorines in ortho position to the para-hydroxyl group) ...

  2. Polychlorinated biphenyl reduction in lake trout by irradiation and broiling

    International Nuclear Information System (INIS)

    Cichy, R.F.; Zabik, M.E.; Weaver, C.M.

    1979-01-01

    The Great Lakes Environmental contaminants surveys (1974-1975) have concluded that excessive concentrations of polychlorinated biphenyls (PCBs) are present in a specific species of lake trout (Salvelinus namaycush). Over 30 ppM of PCBs have been detected in the edible fillet of this fat trout. The objective of this study was to determine the effect of gamma irradiation combined with broiling on the levels of PCBs in lake trout fillets

  3. Polychlorinated Biphenyl Presence in the Columbia River Corridor

    Energy Technology Data Exchange (ETDEWEB)

    R. M. Hermann

    2007-09-06

    The U. S. Department of Energy (DOE) is required by Comprehensive Environmental Response, Compensation, and Liability Act of 1980 regulations to develop a conceptual understanding of potential contaminant releases from the Hanford Site based on an evaluation of existing data and known historical practices. Polychlorinated biphenyls (PCBs) are one environmental contaminant potentially released through leaks, spills, or disposal. This document presents a summary of selected relevant existing information, including environmental studies and Hanford Site analytical data.

  4. Reactivity of polychlorinated biphenyls in nucleophilic and electrophilic substitutions

    Energy Technology Data Exchange (ETDEWEB)

    Gorbunova, Tatyana I., E-mail: gorbunova@ios.uran.ru [I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Kovalevskoy St., 22, Ekaterinburg 620990 (Russian Federation); Subbotina, Julia O. [Ural Federal University named after the first President of Russia B.N. Yeltsin, Mira St., 19, Ekaterinburg 620002 (Russian Federation); Saloutin, Viktor I.; Chupakhin, Oleg N. [I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Kovalevskoy St., 22, Ekaterinburg 620990 (Russian Federation)

    2014-08-15

    Graphical abstract: - Highlights: • Quantum chemical calculations were carried out for PCBs congeners. • Calculated descriptors were used to explain the PCBs reactivity in S{sub N} and S{sub E} substitutions. • Obtained data were used to estimate the PCBs reactivity in the S{sub N} reactions. • Calculated descriptors were insufficient to explain the PCBs reactivity in the S{sub E} reactions. • New neutralization methods of the large-capacity PCBs were discussed. - Abstract: To explain the chemical reactivity of polychlorinated biphenyls in nucleophilic (S{sub N}) and electrophilic (S{sub E}) substitutions, quantum chemical calculations were carried out at the B3LYP/6-31G(d) level of the Density Functional Theory in gas phase. Carbon atomic charges in biphenyl structure were calculated by the Atoms-in-Molecules method. Chemical hardness and global electrophilicity index parameters were determined for congeners. A comparison of calculated descriptors and experimental data for congener reactivity in the S{sub N} and S{sub E} reactions was made. It is shown that interactions in the S{sub N} mechanism are reactions of the hard acid–hard base type, these are the most effective in case of highly chlorinated substrates. To explain the congener reactivity in the S{sub E} reactions, correct descriptors were not established. The obtained results can be used to carry out chemical transformations of the polychlorinated biphenyls in order to prepare them for microbiological destruction or preservation.

  5. Near-IR MCD of the nonheme ferrous active site in naphthalene 1,2-dioxygenase: correlation to crystallography and structural insight into the mechanism of Rieske dioxygenases.

    Science.gov (United States)

    Ohta, Takehiro; Chakrabarty, Sarmistha; Lipscomb, John D; Solomon, Edward I

    2008-02-06

    Near-IR MCD and variable temperature, variable field (VTVH) MCD have been applied to naphthalene 1,2-dioxygenase (NDO) to describe the coordination geometry and electronic structure of the mononuclear nonheme ferrous catalytic site in the resting and substrate-bound forms with the Rieske 2Fe2S cluster oxidized and reduced. The structural results are correlated with the crystallographic studies of NDO and other related Rieske nonheme iron oxygenases to develop molecular level insights into the structure/function correlation for this class of enzymes. The MCD data for resting NDO with the Rieske center oxidized indicate the presence of a six-coordinate high-spin ferrous site with a weak axial ligand which becomes more tightly coordinated when the Rieske center is reduced. Binding of naphthalene to resting NDO (Rieske oxidized and reduced) converts the six-coordinate sites into five-coordinate (5c) sites with elimination of a water ligand. In the Rieske oxidized form the 5c sites are square pyramidal but transform to a 1:2 mixture of trigonal bipyramial/square pyramidal sites when the Rieske center is reduced. Thus the geometric and electronic structure of the catalytic site in the presence of substrate can be significantly affected by the redox state of the Rieske center. The catalytic ferrous site is primed for the O2 reaction when substrate is bound in the active site in the presence of the reduced Rieske site. These structural changes ensure that two electrons and the substrate are present before the binding and activation of O2, which avoids the uncontrolled formation and release of reactive oxygen species.

  6. Complete Reductive Dehalogenation of Brominated Biphenyls by Anaerobic Microorganisms in Sediment

    Science.gov (United States)

    Bedard, Donna L.; Van Dort, Heidi M.

    1998-01-01

    We sought to determine whether microorganisms from the polychlorinated biphenyl (PCB)-contaminated sediment in Woods Pond (Lenox, Mass.) could dehalogenate brominated biphenyls. The PCB dechlorination specificities for the microorganisms in this sediment have been well characterized. This allowed us to compare the dehalogenation specificities for brominated biphenyls and chlorinated biphenyls within a single sediment. Anaerobic sediment microcosms were incubated separately at 25°C with 16 different mono- to tetrabrominated biphenyls (350 μM) and disodium malate (10 mM). Samples were extracted and analyzed by gas chromatography with an electron capture detector and a mass spectrometer detector at various times for up to 54 weeks. All of the tested brominated biphenyls were dehalogenated. For most congeners, including 2,6-dibromobiphenyl (26-BB) and 24-25-BB, the dehalogenation began within 1 to 2 weeks. However, for 246-BB and 2-2-BB, debromination was first observed at 7 and 14 weeks, respectively. Most intermediate products did not persist, but when 2-2-BB was produced as a dehalogenation product, it persisted for at least 15 weeks before it was dehalogenated to 2-BB and then to biphenyl. The dehalogenation specificities for brominated and chlorinated biphenyls were similar: meta and para substituents were generally removed first, and ortho substituents were more recalcitrant. However, the brominated biphenyls were better dehalogenation substrates than the chlorinated biphenyls. All of the tested bromobiphenyls, including those with ortho and unflanked meta and para substituents, were ultimately dehalogenated to biphenyl, whereas their chlorinated counterparts either were not dehalogenation substrates or were only partially dehalogenated. Our data suggest that PCB-dechlorinating microorganisms may be able to dehalogenate brominated biphenyls and may exhibit a relaxed specificity for these substrates. PMID:16349530

  7. 4-Substituted-2-Methoxyphenol: Suitable Building Block to Prepare New Bioactive Natural-like Hydroxylated Biphenyls.

    Science.gov (United States)

    Dettori, Maria Antonietta; Fabbri, Davide; Pisano, Marina; Rozzo, Carla; Palmieri, Giuseppe; Dess, Alessandro; Dallocchio, Roberto; Delogu, Giovanna

    2015-02-01

    A small collection of eugenol- and curcumin-analog hydroxylated biphenyls was prepared by straightforward methods starting from natural 4-substituted-2-methoxyphenols and their antitumoral activity was evaluated in vitro . Two curcumin-biphenyl derivatives showed interesting growth inhibitory activities on different malignant melanoma cell lines with IC 50 ranging from 13 to 1 µM. Preliminary molecular modeling studies were carried out to evaluate conformations and dihedral angles suitable for antiproliferative activity in hydroxylated biphenyls bearing a side aliphatic chain.

  8. Staphylococcus aureus CstB is a novel multidomain persulfide dioxygenase-sulfurtransferase involved in hydrogen sulfide detoxification

    Science.gov (United States)

    Shen, Jiangchuan; Keithly, Mary E.; Armstrong, Richard N.; Higgins, Khadine A.; Edmonds, Katherine A.; Giedroc, David P.

    2016-01-01

    Hydrogen sulfide (H2S) is both a lethal gas and an emerging gasotransmitter in humans, suggesting that cellular H2S level must be tightly regulated. CstB is encoded by the cst operon of the major human pathogen Staphylococcus aureus (S. aureus) and is under the transcriptional control of the persulfide sensor CstR and H2S. Here we show that CstB is a multifunctional Fe(II)-containing persulfide dioxygenase (PDO), analogous to the vertebrate protein ETHE1 (Ethylmalonic Encephalopathy Protein 1). Chromosomal deletion of ethe1 is fatal in vertebrates. In the presence of molecular oxygen (O2), hETHE1 oxidizes glutathione persulfide (GSSH) to generate sulfite and reduced glutathione. In contrast, CstB oxidizes major cellular low molecular weight (LMW) persulfide substrates from S. aureus, coenzyme A persulfide (CoASSH) and bacillithiol persulfide (BSSH), directly to generate thiosulfate (TS) and reduced thiols, thereby avoiding the cellular toxicity of sulfite. Both Cys201 in the N-terminal PDO domain (CstBPDO) and Cys408 in the C-terminal rhodanese domain (CstBRhod) strongly enhance the TS generating activity of CstB. CstB also possesses persulfide transferase (PT; reverse rhodanese) activity which generates TS when provided with LMW persulfides and sulfite, as well as conventional thiosulfate transferase (TST; rhodanese) activity; both activities require Cys408. CstB protects S. aureus against H2S toxicity with C201S and C408S cstB genes unable to rescue a NaHS-induced ΔcstB growth phenotype. Induction of the cst operon by NaHS reveals that functional CstB impacts the cellular TS concentrations. These data collectively suggest that CstB may have evolved to facilitate the clearance of LMW persulfides that occur upon the elevation of the level of cellular H2S and hence may have an impact on bacterial viability under H2S stress, in concert with the other enzymes encoded by the cst operon. PMID:26177047

  9. Role of rhizosphere microorganisms in phytoremediation of biphenyl in a contaminated groundwater plume

    International Nuclear Information System (INIS)

    Sun, B.; Ramsay, J.

    2007-01-01

    This presentation discussed a pump and treat technology used in combination with a phytoremediation technology to remediate a biphenyl contaminated groundwater plume. Biphenyl is used in industrial applications as fungicide and heat transfer agent. It is highly toxic, has poor water solubility and sorbs strongly to soils. Costs for the project were estimated at $860,000 over a period of 20 years, while it was estimated that the addition of phytoremediation would cost only $125,000 over a period of 20 years. The phytoremediation containment area was added to the site which was comprised of a pump and treat system and landfill lagoons. In situ biodegradation of biphenyl was evaluated using microorganisms in poplar and willow rhizospheres. Basal salts were used as a culture medium. Methods to enhance biphenyl degradation were also investigated. Aerobic growth on biphenyl at temperatures of 8 degrees C were measured, and microbial populations were identified. The consortium with the highest biphenyl degradation was then analyzed. Major members were identified as Burkholderia xenovorans LB400 and a strain of Burkholderia xenovorans. Nitrate reduction, sulphate reduction, and methanogens were measured. Enrichment of anaerobic biphenyl degraders. Anaerobic biphenyl degradation was measured after 90 days. Details of anaerobic mineralization experiments were also provided. It was concluded that anaerobic biphenyl degradation was enhanced by TEA and fertilizer addition, as well as by poplar root exudate. tabs., figs

  10. Synergistic Processing of Biphenyl and Benzoate: Carbon Flow Through the Bacterial Community in Polychlorinated-Biphenyl-Contaminated Soil

    Science.gov (United States)

    Leewis, Mary-Cathrine; Uhlik, Ondrej; Leigh, Mary Beth

    2016-02-01

    Aerobic mineralization of PCBs, which are toxic and persistent organic pollutants, involves the upper (biphenyl, BP) and lower (benzoate, BZ) degradation pathways. The activity of different members of the soil microbial community in performing one or both pathways, and their synergistic interactions during PCB biodegradation, are not well understood. This study investigates BP and BZ biodegradation and subsequent carbon flow through the microbial community in PCB-contaminated soil. DNA stable isotope probing (SIP) was used to identify the bacterial guilds involved in utilizing 13C-biphenyl (unchlorinated analogue of PCBs) and/or 13C-benzoate (product/intermediate of BP degradation and analogue of chlorobenzoates). By performing SIP with two substrates in parallel, we reveal microbes performing the upper (BP) and/or lower (BZ) degradation pathways, and heterotrophic bacteria involved indirectly in processing carbon derived from these substrates (i.e. through crossfeeding). Substrate mineralization rates and shifts in relative abundance of labeled taxa suggest that BP and BZ biotransformations were performed by microorganisms with different growth strategies: BZ-associated bacteria were fast growing, potentially copiotrophic organisms, while microbes that transform BP were oligotrophic, slower growing, organisms. Our findings provide novel insight into the functional interactions of soil bacteria active in processing biphenyl and related aromatic compounds in soil, revealing how carbon flows through a bacterial community.

  11. Atom Tunneling in the Hydroxylation Process of Taurine/α-Ketoglutarate Dioxygenase Identified by Quantum Mechanics/Molecular Mechanics Simulations.

    Science.gov (United States)

    Álvarez-Barcia, Sonia; Kästner, Johannes

    2017-06-01

    Taurine/α-ketoglutarate dioxygenase is one of the most studied α-ketoglutarate-dependent dioxygenases (αKGDs), involved in several biotechnological applications. We investigated the key step in the catalytic cycle of the αKGDs, the hydrogen transfer process, by a quantum mechanics/molecular mechanics approach (B3LYP/CHARMM22). Analysis of the charge and spin densities during the reaction demonstrates that a concerted mechanism takes place, where the H atom transfer happens simultaneously with the electron transfer from taurine to the Fe═O cofactor. We found the quantum tunneling of the hydrogen atom to increase the rate constant by a factor of 40 at 5 °C. As a consequence, a quite high kinetic isotope effect close to 60 is obtained, which is consistent with the experimental value.

  12. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

    KAUST Repository

    Brä uer, Alois; Beck, Philipp; Hintermann, Lukas; Groll, Michael

    2015-01-01

    © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.

  13. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

    KAUST Repository

    Bräuer, Alois

    2015-11-10

    © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.

  14. Using "Pseudomonas Putida xylE" Gene to Teach Molecular Cloning Techniques for Undergraduates

    Science.gov (United States)

    Dong, Xu; Xin, Yi; Ye, Li; Ma, Yufang

    2009-01-01

    We have developed and implemented a serial experiment in molecular cloning laboratory course for undergraduate students majored in biotechnology. "Pseudomonas putida xylE" gene, encoding catechol 2, 3-dioxygenase, was manipulated to learn molecular biology techniques. The integration of cloning, expression, and enzyme assay gave students…

  15. Molecular mechanism of strict substrate specificity of an extradiol dioxygenase, DesB, derived from Sphingobium sp. SYK-6.

    Directory of Open Access Journals (Sweden)

    Keisuke Sugimoto

    Full Text Available DesB, which is derived from Sphingobium sp. SYK-6, is a type II extradiol dioxygenase that catalyzes a ring opening reaction of gallate. While typical extradiol dioxygenases show broad substrate specificity, DesB has strict substrate specificity for gallate. The substrate specificity of DesB seems to be required for the efficient growth of S. sp. SYK-6 using lignin-derived aromatic compounds. Since direct coordination of hydroxyl groups of the substrate to the non-heme iron in the active site is a critical step for the catalytic reaction of the extradiol dioxygenases, the mechanism of the substrate recognition and coordination of DesB was analyzed by biochemical and crystallographic methods. Our study demonstrated that the direct coordination between the non-heme iron and hydroxyl groups of the substrate requires a large shift of the Fe (II ion in the active site. Mutational analysis revealed that His124 and His192 in the active site are essential to the catalytic reaction of DesB. His124, which interacts with OH (4 of the bound gallate, seems to contribute to proper positioning of the substrate in the active site. His192, which is located close to OH (3 of the gallate, is likely to serve as the catalytic base. Glu377' interacts with OH (5 of the gallate and seems to play a critical role in the substrate specificity. Our biochemical and structural study showed the substrate recognition and catalytic mechanisms of DesB.

  16. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  17. Health and productivity of dairy cows fed polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Willett, L.B.; Liu, T.T.; Durst, H.I.; Smith, K.L.; Redman, D.R.

    1987-07-01

    Holstein cows were studied through a complete lactation, a nonlactating period, and 42 days of a subsequent lactation for overt and subtle responses to a commercial mixture of polychlorinated biphenyls. Dosed cows (n = 4) received consecutive 60-day periods of daily dosing with 10, 100, and 1000 mg of Aroclor 1254. Control cows (n = 6) received daily sham doses. The following were recorded: daily milk production, feed intake, and health observations; weekly body weight, temperature, heart and respiratory rates and rectal palpation; semi-monthly clinical chemistry determinations; and monthly milk fat, microbiological culture of quarter foremilk samples, and composite milk somatic cell counts. Mean daily milk production (22.4 +/- 1.1 vs 24.8 +/- 1.0 kg) and net energy of a complete lactation (1.46 +/- 0.05 vs 1.45 +/- 0.03 Mcal/kg dry matter intake) were not different (p = 0.85) for control and PCB-dosed cows. Milk production during the first 42 days of the subsequent lactation was also similar for control and dosed cows. Occurrences of injuries, dysfunctions, and general infections were not related to polychlorinated biphenyl exposure. Intramammary infections were detected for both lactations with 51 and 32 infections detected in microbiological cultures, respectively, for the control and dosed groups. Environmental pathogens were most frequently isolated from cases of clinically apparent mastitis. The majority of quarter infections detected were due to Corynebacterium bovis. Only one animal (dosed, necropsy revealed left oviduct obstructed) failed to conceive with three to six services required before conception for the other control and dosed cows. Exposure to polychlorinated biphenyls resulting in maximal residues in milk fat, near 100 micrograms/g, had no apparent effect on health and productivity.

  18. Analytical method of polychlorinated biphenyls(PCBs) in transformer oil

    Energy Technology Data Exchange (ETDEWEB)

    Shin, S.K. [National Institute of Environmental Research, Incheon (Korea); Kim, H.J.; Chung, D.; Kim, K.S.; Kim, J.K.; Chung, Y.H.; Chung, I.R.

    2004-09-15

    Polychlorinated biphenyls (PCBs) is a chlorinated biphenyl compound with the general formula C{sub 12}H{sub 10-n}/Cl{sub n}. PCBs generally occur as mixtures, where n can vary from 1 to 10. The 10 sites available for possible chlorine substitution result in 209 possible PCB congeners. There is now considerable concern regarding; the presence of PCB congeners in insulating oils used within large-scale electrical supply systems. Due to its outstanding chemical and thermal stabilities and electrical insulation properties, the commercial and industrial products of polychlorinated biphenyls (PCBs), such as Aroclors, Kaneclors, Clophens, Phenaclors etc., had been widely used as thermal oil and transformer oil from 1930s until the 1970s. PCBs from a group of persistent organic pollutants of the environment, especially dangerous to living organisms due to high toxicity, persistency, and bio-concentration in adipose tissue. Despite of this fact, PCB-contaminated oils are still commonly encountered partly because PCBs used as dielectric liquids in transformer and condenser. The source of PCBs in environments can range from used transformer oils or dielectric liquids to liquid wastes, and some PCBs contamination is occurred due to the re-use of incompletely reconditioned oil. The current action plan of Republic of Korea dictates that organizations with electrical equipment contaminated with more than 2 mg/L PCBs will need to treat as PCBs-containing wastes, and 50mg/L of PCBs or PCBs equivalent to be treated as a pure PCB preparation. In this study, transformer oils analyzed based on guideline for PCBs analytical method of transformer oil in Korea.

  19. Ideal gas thermodynamic properties for the phenyl, phenoxy, and o-biphenyl radicals

    Science.gov (United States)

    Burcat, A.; Zeleznik, F. J.; Mcbride, B. J.

    1985-01-01

    Ideal gas thermodynamic properties of the phenyl and o-biphenyl radicals, their deuterated analogs and the phenoxy radical were calculated to 5000 K using estimated vibrational frequencies and structures. The ideal gas thermodynamic properties of benzene, biphenyl, their deuterated analogs and phenyl were also calculated.

  20. Degradation of polychlorinated biphenyls (PCBs) using palladized iron

    International Nuclear Information System (INIS)

    West, O.R.; Liang, L.; Holden, W.L.

    1996-06-01

    Contamination from polychlorinated biphenyls (PCBs) is a persistent problem within the Department of Energy complex, as well as in numerous industrial sites around the US. To date, commercially available technologies for destroying these highly stable compounds involve degradation at elevated temperatures either through incineration or base-catalyzed dehalogenation at 300 degrees C. Since the heating required with these processes substantially increases the costs for treatment of PCB-contaminated wastes, there is a need for finding an alternative approach where PCB can be degraded at ambient temperatures. This report describes the degradation of PCB's utilizing the bimetallic substrate of iron/palladium

  1. On the substrate- and stereospecificity of the plant carotenoid cleavage dioxygenase 7

    KAUST Repository

    Bruno, Mark; Hofmann, Manuel; Vermathen, Martina; Alder, Adrian; Beyer, Peter D.; Al-Babili, Salim

    2014-01-01

    Strigolactones are phytohormones synthesized from carotenoids via a stereospecific pathway involving the carotenoid cleavage dioxygenases 7 (CCD7) and 8. CCD7 cleaves 9-cis-β-carotene to form a supposedly 9-cis-configured β-apo-10′-carotenal. CCD8 converts this intermediate through a combination of yet undetermined reactions into the strigolactone-like compound carlactone. Here, we investigated the substrate and stereo-specificity of the Arabidopsis and pea CCD7 and determined the stereo-configuration of the β-apo-10′-carotenal intermediate by using Nuclear Magnetic Resonance Spectroscopy. Our data unequivocally demonstrate the 9-cis-configuration of the intermediate. Both CCD7s cleave different 9-cis-carotenoids, yielding hydroxylated 9-cis-apo-10′-carotenals that may lead to hydroxylated carlactones, but show highest affinity for 9-cis-β-carotene. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Niacin metabolism and indoleamine 2,3-dioxygenase activation in malnourished patients with flaky paint dermatosis.

    Science.gov (United States)

    Maltos, André Luiz; Portari, Guilherme Vannucchi; Moraes, Giselle Vanessa; Monteiro, Marina Casteli Rodrigues; Vannucchi, Helio; da Cunha, Daniel Ferreira

    2015-06-01

    Flaky paint dermatosis, characterized by extensive, often bilateral areas of flaking and pigmentation, mostly in sun unexposed areas is considered a feature of kwashiorkor in both children and adults, and must be differentiated from other dermatosis, including chapped and xerotica skin, and pellagra. In this case series we provide evidence that malnourished patients with flaky paint dermatosis and infection/inflammation shown laboratory data suggestive of indoleamine 2,3-dioxygenase (IDO) activation, besides decreased urinary excretion of N1-methylnicotinamide (N1 MN), a marker of pellagra. We study nine adult patients showing flaky paint dermatosis and clinical features of infection or inflammation, and increased serum C-reactive protein, characteristic of the presence of acute phase response syndrome. As a group, they had low or deficient urinary N1 MN excretion (0.52 ± 0.39 mg/g creatinine) compatible with pellagra. They also showed low serum tryptophan levels (dermatosis showed laboratory data suggestive of IDO activation, besides decreased N1 MN urinary excretion. Taken together, the data support the idea that flaky paint dermatosis could be a skin manifestation of niacin deficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase

    Science.gov (United States)

    Kuehnl, Susanne; Schroecksnadel, Sebastian; Temml, Veronika; Gostner, Johanna M.; Schennach, Harald; Schuster, Daniela; Schwaiger, Stefan; Rollinger, Judith M.; Fuchs, Dietmar; Stuppner, Hermann

    2013-01-01

    Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of C. tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells in vitro methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of C. tinctorius and three lignan derivatives, trachelogenin, arctigenin and matairesinol were isolated. The influence on tryptophan breakdown was investigated in peripheral blood mononuclear cells (PBMCs). Effects were compared to neopterin production in the same cellular assay. Both seed extracts suppressed tryptophan breakdown in stimulated PBMC. The three structurally closely related isolates exerted differing suppressive activity on PBMC: arctigenin (IC50 26.5 μM) and trachelogenin (IC50 of 57.4 μM) showed higher activity than matairesinol (IC50 >200 μM) to inhibit tryptophan breakdown. Effects on neopterin production were similar albeit generally less strong. Data show an immunosuppressive property of compounds which slows down IDO activity. The in vitro results support the view that some of the anti-inflammatory, anti-cancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649

  4. Structural insights into substrate and inhibitor binding sites in human indoleamine 2,3-dioxygenase 1

    Energy Technology Data Exchange (ETDEWEB)

    Lewis-Ballester, Ariel; Pham, Khoa N.; Batabyal, Dipanwita; Karkashon, Shay; Bonanno, Jeffrey B.; Poulos, Thomas L.; Yeh, Syun-Ru (Einstein); (UCI)

    2017-11-22

    Human indoleamine 2,3-dioxygenase 1 (hIDO1) is an attractive cancer immunotherapeutic target owing to its role in promoting tumoral immune escape. However, drug development has been hindered by limited structural information. Here, we report the crystal structures of hIDO1 in complex with its substrate, Trp, an inhibitor, epacadostat, and/or an effector, indole ethanol (IDE). The data reveal structural features of the active site (Sa) critical for substrate activation; in addition, they disclose a new inhibitor-binding mode and a distinct small molecule binding site (Si). Structure-guided mutation of a critical residue, F270, to glycine perturbs the Si site, allowing structural determination of an inhibitory complex, where both the Sa and Si sites are occupied by Trp. The Si site offers a novel target site for allosteric inhibitors and a molecular explanation for the previously baffling substrate-inhibition behavior of the enzyme. Taken together, the data open exciting new avenues for structure-based drug design.

  5. Indoleamine 2,3-dioxygenase and immune changes under antidepressive treatment in major depression in females.

    Science.gov (United States)

    Zoga, Margarita; Oulis, Panagiotis; Chatzipanagiotou, Stylianos; Masdrakis, Vasilios G; Pliatsika, Paraskevi; Boufidou, Fotini; Foteli, Stefania; Soldatos, Constantin R; Nikolaou, Chryssoula; Papageorgiou, Charalampos

    2014-01-01

    Indoleamine 2, 3-dioxygenase (IDO) induction has been suggested as a mechanism by which immune activation affects tryptophan metabolism and serotonin synthesis in major depressive disorder (MDD). We investigated IDO and changes in inflammatory mediators in patients with MDD undergoing effective treatment. Forty female patients with MDD and 40 controls were recruited. Serum IDO was assessed by enzyme-linked immunosorbent assay (ELISA). We also determined tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), C-reactive protein (CRP) and serotonin concentrations. Patients' baseline concentrations of IDO and immune mediators were higher and serotonin concentrations were lower compared to controls. IDO and TNFα concentrations decreased under treatment and IDO changes were positively correlated with patient improvement. IFNγ and CRP concentrations remained unchanged. Serotonin concentration tended to increase. IDO might play an important role in the pathophysiology of MDD. Moreover, antidepressant therapy might reduce IDO production through an IFNγ-independent pathway. Finally, peripheral concentration of IDO assessed by ELISA might be a useful marker of MDD. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Indoleamine 2,3-dioxygenase expression in patients with allergic rhinitis: a case-control study

    Directory of Open Access Journals (Sweden)

    Luukkainen Annika

    2011-12-01

    Full Text Available Abstract Background Indoleamine 2,3-dioxygenase (IDO is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated. Objective Our aim was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis patients allergic to birch pollen during peak exposure to birch pollen allergen and compare it to non-atopic patients. Methods IDO expression was immunohistochemically evaluated from nasal specimens obtained in- and off-season from otherwise healthy non-smoking volunteers both allergic to birch pollen (having mild or moderate allergic rhinoconjunctivitis and non-allergic controls. Results: The IDO expression levels were low in healthy controls and remained low also in patients allergic to birch pollen. There were no differences in the expression of IDO in- and off-season in either healthy or allergic subjects. Conclusions There is a controversy in the role of IDO in upper and lower airways during allergic airway disease. It seems that IDO is associated to allergic inflammations of the lower airways, but does not have a local role in the nasal cavity at least in mild or moderate forms of allergic rhinitis.

  7. Indoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.

    Science.gov (United States)

    de Mattos Barbosa, Mayara Garcia; da Silva Prata, Rhana Berto; Andrade, Priscila Ribeiro; Ferreira, Helen; de Andrade Silva, Bruno Jorge; da Paixão de Oliveira, Jéssica Araújo; Assis, Tayná Quintella; de Toledo-Pinto, Thiago Gomes; de Lima Bezerra, Ohanna Cavalcanti; da Costa Nery, José Augusto; Rosa, Patricia Sammarco; Bozza, Marcelo Torres; Lara, Flávio Alves; Moraes, Milton Ozório; Schmitz, Veronica; Sarno, Euzenir Nunes; Pinheiro, Roberta Olmo

    2017-11-01

    Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO 4 stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites.

    Science.gov (United States)

    Breda, Carlo; Sathyasaikumar, Korrapati V; Sograte Idrissi, Shama; Notarangelo, Francesca M; Estranero, Jasper G; Moore, Gareth G L; Green, Edward W; Kyriacou, Charalambos P; Schwarcz, Robert; Giorgini, Flaviano

    2016-05-10

    Metabolites of the kynurenine pathway (KP) of tryptophan (TRP) degradation have been closely linked to the pathogenesis of several neurodegenerative disorders. Recent work has highlighted the therapeutic potential of inhibiting two critical regulatory enzymes in this pathway-kynurenine-3-monooxygenase (KMO) and tryptophan-2,3-dioxygenase (TDO). Much evidence indicates that the efficacy of KMO inhibition arises from normalizing an imbalance between neurotoxic [3-hydroxykynurenine (3-HK); quinolinic acid (QUIN)] and neuroprotective [kynurenic acid (KYNA)] KP metabolites. However, it is not clear if TDO inhibition is protective via a similar mechanism or if this is instead due to increased levels of TRP-the substrate of TDO. Here, we find that increased levels of KYNA relative to 3-HK are likely central to the protection conferred by TDO inhibition in a fruit fly model of Huntington's disease and that TRP treatment strongly reduces neurodegeneration by shifting KP flux toward KYNA synthesis. In fly models of Alzheimer's and Parkinson's disease, we provide genetic evidence that inhibition of TDO or KMO improves locomotor performance and ameliorates shortened life span, as well as reducing neurodegeneration in Alzheimer's model flies. Critically, we find that treatment with a chemical TDO inhibitor is robustly protective in these models. Consequently, our work strongly supports targeting of the KP as a potential treatment strategy for several major neurodegenerative disorders and suggests that alterations in the levels of neuroactive KP metabolites could underlie several therapeutic benefits.

  9. On the substrate- and stereospecificity of the plant carotenoid cleavage dioxygenase 7

    KAUST Repository

    Bruno, Mark

    2014-05-01

    Strigolactones are phytohormones synthesized from carotenoids via a stereospecific pathway involving the carotenoid cleavage dioxygenases 7 (CCD7) and 8. CCD7 cleaves 9-cis-β-carotene to form a supposedly 9-cis-configured β-apo-10′-carotenal. CCD8 converts this intermediate through a combination of yet undetermined reactions into the strigolactone-like compound carlactone. Here, we investigated the substrate and stereo-specificity of the Arabidopsis and pea CCD7 and determined the stereo-configuration of the β-apo-10′-carotenal intermediate by using Nuclear Magnetic Resonance Spectroscopy. Our data unequivocally demonstrate the 9-cis-configuration of the intermediate. Both CCD7s cleave different 9-cis-carotenoids, yielding hydroxylated 9-cis-apo-10′-carotenals that may lead to hydroxylated carlactones, but show highest affinity for 9-cis-β-carotene. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Functional expression of a valencene dioxygenase from Pleurotus sapidus in E. coli.

    Science.gov (United States)

    Zelena, Kateryna; Krings, Ulrich; Berger, Ralf G

    2012-03-01

    Valencene dioxygenase (ValOx) from the edible basidiomycete Pleurotus sapidus converted the sesquiterpene (+)-valencene to the valuable grapefruit flavour (+)-nootkatone and to nootkatols through intermediate hydroperoxides. Expression of the enzyme was carried out in the cytosol and periplasm of Escherichia coli. The heterologous production led to high yields of inclusion bodies. The poor yield of soluble recombinant protein was improved by various strategies including cold shock expression, chaperone co-expression, and employment of mutant E. coli strains. Up to 60 mg of the biologically active, soluble ValOx was produced by cold shock under control of the cspA promoter at 8 °C in the BL21(DE3)Star strain and co-expression of the E. coli trigger factor. The recombinant enzyme, purified using the N-terminal His tag, showed the catalytic properties of the wild-type enzyme, as was confirmed by the LC-MS analysis of hydroperoxide intermediates and GC-MS analysis of the volatile products. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis

    International Nuclear Information System (INIS)

    Li, L.-A.; Lin, Tsu-Chun Emma

    2007-01-01

    Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium-induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10 -5 M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10 -7 M and CYP11B2 at 10 -9 M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis

  12. Suppression of 9-cis-epoxycarotenoid dioxygenase, which encodes a key enzyme in abscisic acid biosynthesis, alters fruit texture in transgenic tomato.

    Science.gov (United States)

    Sun, Liang; Sun, Yufei; Zhang, Mei; Wang, Ling; Ren, Jie; Cui, Mengmeng; Wang, Yanping; Ji, Kai; Li, Ping; Li, Qian; Chen, Pei; Dai, Shengjie; Duan, Chaorui; Wu, Yan; Leng, Ping

    2012-01-01

    Cell wall catabolism during fruit ripening is under complex control and is key for fruit quality and shelf life. To examine the role of abscisic acid (ABA) in tomato (Solanum lycopersicum) fruit ripening, we suppressed SlNCED1, which encodes 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in the biosynthesis of ABA. To suppress SlNCED1 specifically in tomato fruits, and thus avoid the pleiotropic phenotypes associated with ABA deficiency, we used an RNA interference construct driven by the fruit-specific E8 promoter. ABA accumulation and SlNCED1 transcript levels in the transgenic fruit were down-regulated to between 20% and 50% of the levels measured in the control fruit. This significant reduction in NCED activity led to a down-regulation in the transcription of genes encoding major cell wall catabolic enzymes, specifically polygalacturonase (SlPG), pectin methyl esterase (SlPME), β-galactosidase precursor mRNA (SlTBG), xyloglucan endotransglycosylase (SlXET), endo-1,4-β-cellulose (SlCels), and expansin (SlExp). This resulted in an increased accumulation of pectin during ripening. In turn, this led to a significant extension of the shelf life to 15 to 29 d compared with a shelf life of only 7 d for the control fruit and an enhancement of fruit firmness at the mature stage by 30% to 45%. In conclusion, ABA affects cell wall catabolism during tomato fruit ripening via down-regulation of the expression of major catabolic genes (SlPG, SlPME, SlTBG, SlXET, SlCels, and SlExp).

  13. Suppression of 9-cis-Epoxycarotenoid Dioxygenase, Which Encodes a Key Enzyme in Abscisic Acid Biosynthesis, Alters Fruit Texture in Transgenic Tomato1[W][OA

    Science.gov (United States)

    Sun, Liang; Sun, Yufei; Zhang, Mei; Wang, Ling; Ren, Jie; Cui, Mengmeng; Wang, Yanping; Ji, Kai; Li, Ping; Li, Qian; Chen, Pei; Dai, Shengjie; Duan, Chaorui; Wu, Yan; Leng, Ping

    2012-01-01

    Cell wall catabolism during fruit ripening is under complex control and is key for fruit quality and shelf life. To examine the role of abscisic acid (ABA) in tomato (Solanum lycopersicum) fruit ripening, we suppressed SlNCED1, which encodes 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in the biosynthesis of ABA. To suppress SlNCED1 specifically in tomato fruits, and thus avoid the pleiotropic phenotypes associated with ABA deficiency, we used an RNA interference construct driven by the fruit-specific E8 promoter. ABA accumulation and SlNCED1 transcript levels in the transgenic fruit were down-regulated to between 20% and 50% of the levels measured in the control fruit. This significant reduction in NCED activity led to a down-regulation in the transcription of genes encoding major cell wall catabolic enzymes, specifically polygalacturonase (SlPG), pectin methyl esterase (SlPME), β-galactosidase precursor mRNA (SlTBG), xyloglucan endotransglycosylase (SlXET), endo-1,4-β-cellulose (SlCels), and expansin (SlExp). This resulted in an increased accumulation of pectin during ripening. In turn, this led to a significant extension of the shelf life to 15 to 29 d compared with a shelf life of only 7 d for the control fruit and an enhancement of fruit firmness at the mature stage by 30% to 45%. In conclusion, ABA affects cell wall catabolism during tomato fruit ripening via down-regulation of the expression of major catabolic genes (SlPG, SlPME, SlTBG, SlXET, SlCels, and SlExp). PMID:22108525

  14. Implication of Tryptophan 2,3-Dioxygenase and its Novel Variants in the Hippocampus and Cerebellum During the Developing and Adult Brain

    Directory of Open Access Journals (Sweden)

    Masaaki Kanai

    2010-07-01

    Full Text Available Tryptophan 2,3-dioxygenase (TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo-/-mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form, tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro. While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed.

  15. Implication of Tryptophan 2,3-Dioxygenase and its Novel Variants in the Hippocampus and Cerebellum during the Developing and Adult Brain

    Directory of Open Access Journals (Sweden)

    Masaaki Kanai

    2010-01-01

    Full Text Available Tryptophan 2,3-dioxygenase (TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo −/− mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form, tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro . While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed.

  16. Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

    International Nuclear Information System (INIS)

    Li, L.-A.; Wang, P.-W.; Chang, Louis W.

    2004-01-01

    To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

  17. Biobatteries and biofuel cells with biphenylated carbon nanotubes

    Science.gov (United States)

    Stolarczyk, Krzysztof; Kizling, Michał; Majdecka, Dominika; Żelechowska, Kamila; Biernat, Jan F.; Rogalski, Jerzy; Bilewicz, Renata

    2014-03-01

    Single-walled carbon nanotubes (SWCNTs) covalently biphenylated are used for the construction of cathodes in a flow biobattery and in flow biofuel cell. Zinc covered with a hopeite layer is the anode in the biobattery and glassy carbon electrode covered with bioconjugates of single-walled carbon nanotubes with glucose oxidase and catalase is the anode of the biofuel cell. The potentials of the electrodes are measured vs. the Ag/AgCl reference electrode under changing loads of the fuel cell/biobattery. The power density of the biobattery with biphenylated nanotubes at the cathode is ca. 0.6 mW cm-2 and the open circuit potential is ca. 1.6 V. In order to obtain larger power densities and voltages three biobatteries are connected in a series which leads to the open circuit potential of ca. 4.8 V and power density 2.1 mW cm-2 at 3.9 V under 100 kΩ load. The biofuel cell shows power densities of ca. 60 μW cm-2 at 20 kΩ external resistance but the open circuit potential for such biofuel cell is only 0.5 V. The biobattery showing significantly larger power densities and open circuit voltages are especially useful for testing novel cathodes and applications such as powering units for clocks and sensing devices.

  18. Momentum space analysis of the electronic structure of biphenyl

    International Nuclear Information System (INIS)

    Morini, F; Shojaei, S H Reza; Deleuze, M S

    2014-01-01

    The results of a yet to come experimental study of the electronic structure of biphenyl employing electron momentum spectroscopy (EMS) have been theoretically predicted, taking into account complications such as structural mobility in the electronic ground state, electronic correlation and relaxation, and a dispersion of the inner-valence ionization intensity to electronically excited (shake-up) configurations in the cation. The main purpose of this work is to explore the current limits of EMS in unraveling details of the molecular structure, namely the torsional characteristics of large and floppy aromatic molecules. At the benchmark ADC(3)/cc-pVDZ level of theory, the influence of the twist angle between the two phenyl rings is found to be extremely limited, except for individual orbital momentum profiles corresponding to ionization lines at electron binding energies ranging from 15 to 18 eV. When taking band overlap effects into account, this influence is deceptively far too limited to allow for any experimental determination of the torsional characteristics of biphenyl by means of EMS. (paper)

  19. Mutational analysis of the HGO gene in Finnish alkaptonuria patients

    Science.gov (United States)

    de Bernabe, D. B.-V.; Peterson, P.; Luopajarvi, K.; Matintalo, P.; Alho, A.; Konttinen, Y.; Krohn, K.; de Cordoba, S. R.; Ranki, A.

    1999-01-01

    Alkaptonuria (AKU), the prototypic inborn error of metabolism, has recently been shown to be caused by loss of function mutations in the homogentisate-1,2-dioxygenase gene (HGO). So far 17 mutations have been characterised in AKU patients of different ethnic origin. We describe three novel mutations (R58fs, R330S, and H371R) and one common AKU mutation (M368V), detected by mutational and polymorphism analysis of the HGO gene in five Finnish AKU pedigrees. The three novel AKU mutations are most likely specific for the Finnish population and have originated recently.


Keywords: alkaptonuria; homogentisate-1,2-dioxygenase; Finland PMID:10594001

  20. Indoleamine 2,3-dioxygenase and regulatory T cells in acute myeloid leukemia.

    Science.gov (United States)

    Mansour, Iman; Zayed, Rania A; Said, Fadwa; Latif, Lamyaa Abdel

    2016-09-01

    The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Thirty-seven adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology, and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (P = 0.002 and P < 0.001, respectively). A positive correlation was found between IDO expression and Tregs percentage (P value = 0.012, r = 0.5). In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which could have an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

  1. Resonance Raman study on indoleamine 2,3-dioxygenase: Control of reactivity by substrate-binding

    Energy Technology Data Exchange (ETDEWEB)

    Yanagisawa, Sachiko; Hara, Masayuki [Graduate School of Life Science and Picobiology Institute, University of Hyogo, Koto 3-2-1, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); Sugimoto, Hiroshi; Shiro, Yoshitsugu [Biometal Science Laboratory, RIKEN SPring-8 Center, Harima Institute, Koto 1-1-1, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Ogura, Takashi, E-mail: ogura@sci.u-hyogo.ac.jp [Graduate School of Life Science and Picobiology Institute, University of Hyogo, Koto 3-2-1, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan)

    2013-06-20

    Highlights: • Indoleamine 2,3-dioygenase has been studied by resonance Raman spectroscopy. • Trp-binding to the enzyme induces high frequency shift of the Fe–His stretching mode. • Increased imidazolate character of histidine promotes the O–O bond cleavage step. • A fine-tuning of the reactivity of the O–O bond cleavage reaction is identified. • The results are consistent with the sequential oxygen-atom-transfer mechanism. - Abstract: Resonance Raman spectra of ligand-bound complexes including the 4-phenylimidazole complex and of free and L-Trp-bound forms of indoleamine 2, 3-dioxygenase in the ferric state were examined. Effects on the vinyl and propionate substituent groups of the heme were detected in a ligand-dependent fashion. The effects of phenyl group of 4-phenylimidazole on the vinyl and propionate Raman bands were evident when compared with the case of imidazole ligand. Substrate binding to the ferrous protein caused an upshift of the iron–histidine stretching mode by 3 cm{sup −1}, indicating an increase in negativity of the imidazole ring, which favors the O–O bond cleavage. The substrate binding event is likely to be communicated from the heme distal side to the iron–histidine bond through heme substituent groups and the hydrogen-bond network which includes water molecules, as identified in an X-ray structure of a 4-phenylimidazole complex. The results provide evidence for fine-tuning of the reactivity of O–O bond cleavage by the oxygenated heme upon binding of L-Trp.

  2. Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients.

    Science.gov (United States)

    Adu-Gyamfi, Clement G; Snyman, Tracy; Hoffmann, Christopher J; Martinson, Neil A; Chaisson, Richard E; George, Jaya A; Suchard, Melinda S

    2017-10-15

    There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  3. Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice

    Directory of Open Access Journals (Sweden)

    Carlos R. Dostal

    2017-12-01

    Full Text Available Stressors activate the hypothalamic-pituitary-adrenal (HPA axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2. Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent. Thus, C57BL/6J mice were used to characterize DO expression in brain-regions, astrocytes and microglia to characterize restraint-stress-induced DO expression. Stress increased kynurenine in brain and plasma, demonstrating increased DO activity. Of three Ido1 transcripts, only Ido1-v1 expression was increased by stress and within astrocytes, not microglia, indicating transcript- and glial-specificity. Stress increased Ido1-v1 only in frontal cortex and hypothalamus, indicating brain-region specificity. Of eight Ido2 transcripts, Ido2-v3 expression was increased by stress, again only within astrocytes. Likewise, stress increased Tdo2-FL expression in astrocytes, not microglia. Interestingly, Ido2 and Tdo2 transcripts were not correspondingly induced in Ido1-knockout (Ido1KO mice, suggesting that Ido1 is necessary for the central DO response to acute stress. Unlike acute inflammatory models resulting in DO induction within microglia, only astrocyte DO expression was increased by acute restraint-stress, defining their unique role during stress-dependent activation of the Kynurenine Pathway. Keywords: Stress, Ido, Tdo, Kynurenine, Astrocyte, Liver

  4. The selenazal drug ebselen potently inhibits indoleamine 2,3-dioxygenase by targeting enzyme cysteine residues.

    Science.gov (United States)

    Terentis, Andrew C; Freewan, Mohammed; Sempértegui Plaza, Tito S; Raftery, Mark J; Stocker, Roland; Thomas, Shane R

    2010-01-26

    The heme enzyme indoleamine 2,3-dioxygenase (IDO) plays an important immune regulatory role by catalyzing the oxidative degradation of l-tryptophan. Here we show that the selenezal drug ebselen is a potent IDO inhibitor. Exposure of human macrophages to ebselen inhibited IDO activity in a manner independent of changes in protein expression. Ebselen inhibited the activity of recombinant human IDO (rIDO) with an apparent inhibition constant of 94 +/- 17 nM. Optical and resonance Raman spectroscopy showed that ebselen altered the active site heme of rIDO by inducing a transition of the ferric heme iron from the predominantly high- to low-spin form and by lowering the vibrational frequency of the Fe-CO stretch of the CO complex, indicating an opening of the distal heme pocket. Substrate binding studies showed that ebselen enhanced nonproductive l-tryptophan binding, while circular dichroism indicated that the drug reduced the helical content and protein stability of rIDO. Thiol labeling and mass spectrometry revealed that ebselen reacted with multiple cysteine residues of IDO. Removal of cysteine-bound ebselen with dithiothreitol reversed the effects of the drug on the heme environment and significantly restored enzyme activity. These findings indicate that ebselen inhibits IDO activity by reacting with the enzyme's cysteine residues that result in changes to protein conformation and active site heme, leading to an increase in the level of nonproductive substrate binding. This study highlights that modification of cysteine residues is a novel and effective means of inhibiting IDO activity. It also suggests that IDO is under redox control and that the enzyme represents a previously unrecognized in vivo target of ebselen.

  5. Stepwise O-Atom Transfer in Heme-Based Tryptophan Dioxygenase: Role of Substrate Ammonium in Epoxide Ring Opening.

    Science.gov (United States)

    Shin, Inchul; Ambler, Brett R; Wherritt, Daniel; Griffith, Wendell P; Maldonado, Amanda C; Altman, Ryan A; Liu, Aimin

    2018-03-28

    Heme-based tryptophan dioxygenases are established immunosuppressive metalloproteins with significant biomedical interest. Here, we synthesized two mechanistic probes to specifically test if the α-amino group of the substrate directly participates in a critical step of the O atom transfer during catalysis in human tryptophan 2,3-dioxygenase (TDO). Substitution of the nitrogen atom of the substrate to a carbon (probe 1) or oxygen (probe 2) slowed the catalytic step following the first O atom transfer such that transferring the second O atom becomes less likely to occur, although the dioxygenated products were observed with both probes. A monooxygenated product was also produced from probe 2 in a significant quantity. Analysis of this new product by HPLC coupled UV-vis spectroscopy, high-resolution mass spectrometry, 1 H NMR, 13 C NMR, HSQC, HMBC, and infrared (IR) spectroscopies concluded that this monooxygenated product is a furoindoline compound derived from an unstable epoxyindole intermediate. These results prove that small molecules can manipulate the stepwise O atom transfer reaction of TDO and provide a showcase for a tunable mechanism by synthetic compounds. The product analysis results corroborate the presence of a substrate-based epoxyindole intermediate during catalysis and provide the first substantial experimental evidence for the involvement of the substrate α-amino group in the epoxide ring-opening step during catalysis. This combined synthetic, biochemical, and biophysical study establishes the catalytic role of the α-amino group of the substrate during the O atom transfer reactions and thus represents a substantial advance to the mechanistic comprehension of the heme-based tryptophan dioxygenases.

  6. Stereospecific oxidation of (R)- and (S)-1-indanol by naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4.

    OpenAIRE

    Lee, K; Resnick, S M; Gibson, D T

    1997-01-01

    A recombinant Escherichia coli strain which expresses naphthalene dioxygenase (NDO) from Pseudomonas sp. strain NCIB 9816-4 oxidized (S)-1-indanol to trans-(1S,3S)-indan-1,3-diol (95.5%) and (R)-3-hydroxy-1-indanone (4.5%). The same cells oxidized (R)-1-indanol to cis-1,3-indandiol (71%), (R)-3-hydroxy-1-indanone (18.2%), and cis-1,2,3-indantriol (10.8%). Purified NDO oxidized (S)-1-indenol to both syn- and anti-2,3-dihydroxy-1-indanol.

  7. Stereospecific oxidation of (R)- and (S)-1-indanol by naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4.

    Science.gov (United States)

    Lee, K; Resnick, S M; Gibson, D T

    1997-05-01

    A recombinant Escherichia coli strain which expresses naphthalene dioxygenase (NDO) from Pseudomonas sp. strain NCIB 9816-4 oxidized (S)-1-indanol to trans-(1S,3S)-indan-1,3-diol (95.5%) and (R)-3-hydroxy-1-indanone (4.5%). The same cells oxidized (R)-1-indanol to cis-1,3-indandiol (71%), (R)-3-hydroxy-1-indanone (18.2%), and cis-1,2,3-indantriol (10.8%). Purified NDO oxidized (S)-1-indenol to both syn- and anti-2,3-dihydroxy-1-indanol.

  8. Purification and properties of protocatechuate 3,4-dioxygenase from Chaetomium piluliferum induced with p-hydroxybenzoic acid.

    Science.gov (United States)

    Wojtaś-Wasilewska, M; Trojanowski, J

    1980-01-01

    1. Protocatechuate 3,4-dioxygenase (protocatechuate : oxygen 3,4-oxidoreductase, EC 1.13.11.3) was isolated from mycelium of Chaetomium piluliferum induced with p-hydroxybenzoic acid. The enzyme was purified about 80-fold by ammonium sulphate fractionation and DEAE-cellulose and Sephadex G-200 chromatography, and was homogeneous on polyacrylamide-gel electrophoresis. 2. The enzyme showed high substrate specificity; its pH optimum was 7.5-8.0, and molecula weight about 76 000 as determined by filtration on Sephadex G-200. The Michaelis constant for protocatechuic acid was 11.1 microM.

  9. Polychlorinated biphenyls: persistent pollutants with immunological, neurological, and endocrinological consequences.

    Science.gov (United States)

    Crinnion, Walter J

    2011-03-01

    Polychlorinated biphenyls (PCBs) are considered "persistent organic pollutants;" fat-soluble compounds that bioaccumulate in individuals and bio-magnify in the food chain. PCBs were the first industrial compounds to experience a worldwide ban on production because of their potent toxicity. These compounds are still present in our food supply (fish, dairy, hamburger, and poultry being the most contaminated) and our bodies. Once in the body, they can cause long-term problems, especially for those exposed in utero. PCB bioaccumulation can lead to reduced infection fighting ability, increased rates of autoimmunity, cognitive and behavioral problems, and hypothyroidism. Some research also links PCBs to increased rates of type 2 diabetes. Testing is currently available for some of the most damaging PCBs. The testing compares individual levels to national reference values and can be interpreted to determine current exposure. Dietary measures can be enacted that will reduce PCB half-lives in humans by increasing excretion.

  10. Vapor solvent decontamination of PCB [polychlorinated biphenyls] transformer components

    International Nuclear Information System (INIS)

    Green, G.R.; Green, G.R.

    1992-01-01

    A process is provided to recover reclaimable material from discarded transformers containing PCB (polychlorinated biphenyl) insulating oils and to minimize the volume of materials which are subject to environmental regulation upon disposal. According to the invention, the transformer is drained and given an initial cleaning. The internal parts are removed and cleaned a second time as is the empty transformer casing. Recoverable materials such as aluminum and copper are cleaned to less than 10 μg of PCB per 100 cm 2 , allowing these materials to be recycled rather than buried. Almost all of the remaining nonmetallic materials are combustible solids or liquids which can be destroyed by incineration. The cleaning is accomplished using trichloroethylene solvent, chosen for its low boiling point which makes it easy to recycle using an isothermal separator. The removed transformer parts are cleaned in a secondary cleaning station consisting of 3 separate sections including tumbling baskets. 2 figs

  11. Kinetics of polychlorinated biphenyl partitioning to marine Chrysophyte Isochrysis galbana

    International Nuclear Information System (INIS)

    Ko, Fung-Chi; Baker, Joel E.; Tew, Kwee S.

    2012-01-01

    This study focused on the uptake kinetics of polychlorinated biphenyl (PCB) congeners by the Chrysophyte, Isochrysis galbana. A gas-purging experimental system was used to maintain constant dissolved PCB concentrations. Three phases of absorption were observed: first, a rapid absorption phase within the first 15 min, second, a first order process reaching the maximum concentration within 48 h of exposure, and third, a plateau phase as yet to be determined with very slight increases in concentration. In this study, the percentage of the maximum concentration reached within the first phase varied from 10% to 67%, depending on the size of the PCB (as determined by molecular weight and total surface area), whereas the uptake rate (k u ) during the second phase was more comparable across different PCBs. In addition, for the first phase, the bioconcentration factor (BCF) of PCBs deviated from its expected relationship with hydrophobicity, as determined by K ow , and was instead related to the molecular structure of the compound.

  12. Guidance on the management of polychlorinated biphenyls (PCBs)

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-01

    Polychlorinated biphenyls (PCBs) are a class of synthetic organic chemicals including 209 known isomers, each with from 1 to 10 chlorine atoms on a biphenyl ring. PCBs have a number of desirable properties for industrial applications including thermal stability, flame retardance, and low vapor pressure. Because of these properties, PCBs were widely used as dielectric fluid in electrical equipment such as utility transformers and capacitors. PCBs were also extensively used in hydraulic fluid and heat transfer fluid, in gaskets, as additives in cutting oils and lubricant, and in a variety of other uses. The Toxic Substances Control Act (TSCA) banned the manufacture of PCBs after 1978 in response to emerging information about the adverse health effects of PCBs and their persistence in the environment. In addition, TSCA directed the Administrator of the Environmental Protection Agency (EPA) to prescribe methods for disposal of PCBS, require marking of PCBs with warning labels, and control their use. The TSCA regulations allow continued use of PCBs provided that the use is totally enclosed and does not pose a risk to human health or the environment. However, at the end of their useful life, all PCB materials must be disposed of according to the TSCA regulations. This guidance document uses graphics and flow charts where possible to present the TSCA regulations according to management activities such as use, storage, disposal, and spill cleanup. The document is designed to be read on an as-needed basis; that is, each chapter can stand alone or may be read in combination with others to help the reader determine the regulations relevant to his or her individual situation and needs. Every attempt has been made to include the requirements of other statutes and regulations that apply to PCB materials and provide references for the reader to consult for additional information.

  13. Spermatogenic capacity in fertile men with elevated exposure to polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Petersen, Maria Skaalum; Halling, Jónrit; Weihe, Pál

    2015-01-01

    BACKGROUND: Endocrine disrupting industrial chemicals, such as polychlorinated biphenyls (PCBs), are suspected to adversely affect male reproductive functions. OBJECTIVES: The Faroe Islands community exhibits an unusually wide range of exposures to dietary contaminants, and in this setting we...

  14. CATALYTIC STEAM REFORMING OF CHLOROCARBONS: POLYCHLORINATED BIPHENYLS (PCBS). (R826694C633)

    Science.gov (United States)

    Experiments with commercial askarals (Aroclors 1221, 1248 and 1254) have confirmed the feasibility of catalytic steam reforming as a method for destroying polychlorinated biphenyls (PCBs). Rhodium, platinum and nickel supported on Preliminary results of the comparison of the electrochemical behavior of a thioether and biphenyl

    Science.gov (United States)

    Morales, W.; Jones, W. R.

    1983-01-01

    An electrochemical cell was constructed to explore the feasibility of using electrochemical techniques to simulate the tribochemistry of various substances. The electrochemical cell was used to study and compare the behavior of a thioether 1,3-bis(phenylthio) benzene and biphenyl. It is found that under controlled conditions biphenyl undergoes a reversible reduction to a radical anion whereas the thioether undergoes an irreversible reduction yielding several products. The results are discussed in relationship to boundary lubrication.

  15. Influence of Aroclor 1242 Concentration on Polychlorinated Biphenyl Biotransformations in Hudson River Test Tube Microcosms

    Science.gov (United States)

    Fish, K. M.

    1996-01-01

    When 93.3 to 933 (mu)mol of Aroclor 1242 per kg was added to Hudson River sediment test tube microcosms, the rates of polychlorinated biphenyl biotransformations increased with increasing Aroclor 1242 concentration after a 4- to 8-week acclimation period. In contrast, when 37.3 (mu)mol of Aroclor 1242 per kg was added, polychlorinated biphenyl biotransformations occurred at slow constant rates. PMID:16535387

  16. The effects of trace elements, cations, and environmental conditions on protocatechuate 3,4-dioxygenase activity

    Directory of Open Access Journals (Sweden)

    Andréa Scaramal da Silva

    2013-04-01

    Full Text Available Phenanthracene is a highly toxic organic compound capable of contaminating water and soils, and biodegradation is an important tool for remediating polluted environments. This study aimed to evaluate the effects of trace elements, cations, and environmental conditions on the activity of the protocatechol 3,4-dioxygenase (P3,4O enzyme produced by the isolate Leifsonia sp. in cell-free and immobilized extracts. The isolate was grown in Luria Bertani broth medium (LB amended with 250 mg L-1 of phenanthrene. Various levels of pH (4.0-9.0, temperature (5-80 °C, time (0-90 min, trace elements (Cu2+, Hg2+ and Fe3+, and cations (Mg2+, Mn2+, K+ and NH4+ were tested to determine which conditions optimized enzyme activity. In general, the immobilized extract exhibited higher enzyme activity than the cell-free extract in the presence of trace elements and cations. Adding iron yielded the highest relative activity for both cell-free and immobilized extracts, with values of 16 and 99 %, respectively. Copper also increased enzyme activity for both cell-free and immobilized extracts, with values of 8 and 44 %, respectively. Enzyme activity in the phosphate buffer was high across a wide range of pH, reaching 80 % in the pH range between 6.5 and 8.0. The optimum temperatures for enzyme activity differed for cell-free and immobilized extracts, with maximum enzyme activity observed at 35 ºC for the cell-free extract and at 55 ºC for the immobilized extract. The cell-free extract of the P3,4O enzyme exhibited high activity only during the first 3 min of incubation, when it showed 50 % relative activity, and dropped to 0 % after 60 min of incubation. By contrast, activity in the immobilized extract was maintained during 90 min of incubation. This isolate has important characteristics for phenanthrene biodegradation, producing high quantities of the P3,4O enzyme that forms part of the most important pathway for PAH biodegradation.

  17. The Relationships among Tryptophan, Kynurenine, Indoleamine 2,3-Dioxygenase, Depression, and Neuropsychological Performance.

    Science.gov (United States)

    Hestad, Knut A; Engedal, Knut; Whist, Jon E; Farup, Per G

    2017-01-01

    It has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO) is a biological mediator of inflammation related to the psychopathology of depression, with a Kynurenine (KYN) increase in the Tryptophan (TRP) metabolic pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and the ratio of KYN to TRP concentrations × 10 3 (KT Ratio) in serum and cerebrospinal fluid (CSF) in (a) a group of depressed patients and (b) a control group of patients referred to a neurologic outpatient clinic for whom no specific diagnosis could be established. The KT Ratio is considered an index that represents IDO. The participants were examined with the Beck Depression Inventory II (BDI-II), the Montgomery Aasberg Depression Rating Scale (MADRS), and a neuropsychological test battery. We found no significant differences between the two study groups with respect to TRP, KYN, or KT Ratio in serum or CSF. Differences in neuropsychological performance between the two patient groups could be seen in the following tests: Animal Fluency, Digit Symbol, the DKEFS Color-Interference Test (Naming Part), Trail Making Test A and B, and the Grooved Pegboard Non-dominant Hand. KYN in serum correlated highly with KYN in CSF. KYN in serum correlated significantly with both age and gender. When analyzing males and females separately, we found that women had a lower level of TRP in both serum (Mann-Whitney U -test: TRP in Serum; p = 0.001) and CSF (Mann-Whitney U -test: TRP in CSF; p = 0.003). Women had a lower level of KYN in serum ( p = 0.029) than men did. Age was positively associated with KYN. KYN in CSF correlated only with age, however; there were no gender differences. No significant relationship was seen between BDI-II and MADRS on the one hand, and KYN and TRP on the other. KYN in CSF as the KT Ratio in both serum and CSF was associated with neuropsychological performance. Thus, we suggest that KYN and KT Ratio are related more strongly to

  18. The Relationships among Tryptophan, Kynurenine, Indoleamine 2,3-Dioxygenase, Depression, and Neuropsychological Performance

    Directory of Open Access Journals (Sweden)

    Knut A. Hestad

    2017-10-01

    Full Text Available It has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO is a biological mediator of inflammation related to the psychopathology of depression, with a Kynurenine (KYN increase in the Tryptophan (TRP metabolic pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and the ratio of KYN to TRP concentrations × 103 (KT Ratio in serum and cerebrospinal fluid (CSF in (a a group of depressed patients and (b a control group of patients referred to a neurologic outpatient clinic for whom no specific diagnosis could be established. The KT Ratio is considered an index that represents IDO. The participants were examined with the Beck Depression Inventory II (BDI-II, the Montgomery Aasberg Depression Rating Scale (MADRS, and a neuropsychological test battery. We found no significant differences between the two study groups with respect to TRP, KYN, or KT Ratio in serum or CSF. Differences in neuropsychological performance between the two patient groups could be seen in the following tests: Animal Fluency, Digit Symbol, the DKEFS Color-Interference Test (Naming Part, Trail Making Test A and B, and the Grooved Pegboard Non-dominant Hand. KYN in serum correlated highly with KYN in CSF. KYN in serum correlated significantly with both age and gender. When analyzing males and females separately, we found that women had a lower level of TRP in both serum (Mann–Whitney U-test: TRP in Serum; p = 0.001 and CSF (Mann–Whitney U-test: TRP in CSF; p = 0.003. Women had a lower level of KYN in serum (p = 0.029 than men did. Age was positively associated with KYN. KYN in CSF correlated only with age, however; there were no gender differences. No significant relationship was seen between BDI-II and MADRS on the one hand, and KYN and TRP on the other. KYN in CSF as the KT Ratio in both serum and CSF was associated with neuropsychological performance. Thus, we suggest that KYN and KT Ratio are related more strongly to

  19. Immuno-regulatory function of indoleamine 2,3 dioxygenase through modulation of innate immune responses.

    Directory of Open Access Journals (Sweden)

    Malihe-Sadat Poormasjedi-Meibod

    Full Text Available Successful long-term treatment of type-1 diabetes mainly relies on replacement of β-cells via islet transplantation. Donor shortage is one of the main obstacles preventing transplantation from becoming the treatment of choice. Although animal organs could be an alternative source for transplantation, common immunosuppressive treatments demonstrate low efficacy in preventing xenorejection. Immunoprotective effects of indoleamine 2,3-dioxygenase (IDO on T-cell mediated allorejection has been extensively studied. Our studies revealed that IDO expression by fibroblasts, induced apoptosis in T-cells while not affecting non-immune cell survival/function. Since macrophages play a pivotal role in xenograft rejection, herein we investigated the effect of IDO-induced tryptophan deficiency/kynurenine accumulation on macrophage function/survival. Moreover, we evaluated the local immunosuppressive effect of IDO on islet-xenograft protection. Our results indicated that IDO expression by bystander fibroblasts significantly reduced the viability of primary macrophages via apoptosis induction. Treatment of peritoneal macrophages by IDO-expressing fibroblast conditioned medium significantly reduced their proinflammatory activity through inhibition of iNOS expression. To determine whether IDO-induced tryptophan starvation or kynurenine accumulation is responsible for macrophage apoptosis and inhibition of their proinflammatory activity, Raw264.7 cell viability and proinflammatory responses were evaluated in tryptophan deficient medium or in the presence of kynurenine. Tryptophan deficiency, but not kynurenine accumulation, reduced Raw264.7 cell viability and suppressed their proinflammatory activity. Next a three-dimensional islet-xenograft was engineered by embedding rat islets within either control or IDO-expressing fibroblast-populated collagen matrix. Islets morphology and immune cell infiltration were then studied in the xenografts transplanted into the C57

  1. Regional analysis of potential polychlorinated biphenyl degrading bacterial strains from China

    Directory of Open Access Journals (Sweden)

    Jianjun Shuai

    Full Text Available ABSTRACT Polychlorinated biphenyls (PCBs, the chlorinated derivatives of biphenyl, are one of the most prevalent, highly toxic and persistent groups of contaminants in the environment. The objective of this study was to investigate the biodegradation of PCBs in northeastern (Heilongjiang Province, northern (Shanxi Province and eastern China (Shanghai municipality. From these areas, nine soil samples were screened for PCB-degrading bacteria using a functional complementarity method. The genomic 16S rDNA locus was amplified and the products were sequenced to identify the bacterial genera. Seven Pseudomonas strains were selected to compare the capacity of bacteria from different regions to degrade biphenyl by HPLC. Compared to the biphenyl content in controls of 100%, the biphenyl content went down to 3.7% for strain P9-324, 36.3% for P2-11, and 20.0% for the other five strains. These results indicate that a longer processing time led to more degradation of biphenyl. PCB-degrading bacterial strains are distributed differently in different regions of China.

  2. Identification of an evolutionary conserved structural loop that is required for the enzymatic and biological function of tryptophan 2,3-dioxygenase

    NARCIS (Netherlands)

    Michels, Helen; Seinstra, Renee I.; Uitdehaag, Joost C. M.; Koopman, Mandy; van Faassen, Martijn; Martineau, Celine N.; Kema, Ido P.; Buijsman, Rogier; Nollen, Ellen A. A.

    2016-01-01

    The enzyme TDO (tryptophan 2,3-dioxygenase; TDO-2 in Caenorhabditis elegans) is a potential therapeutic target to cancer but is also thought to regulate proteotoxic events seen in the progression of neurodegenerative diseases. To better understand its function and develop specific compounds that

  3. Increased Tregs associated with elevated Indoleamine-2,3-dioxygenase activity and an imbalanced Kynurenine pathway in IFNpositive primary Sjögren's syndrome

    NARCIS (Netherlands)

    N.I. Maria (Naomi); C.G. van Helden-Meeuwsen; Z. Brkić (Zana); S.M.J. Paulissen (Sandra); E.C. Steenwijk (Eline); V.A.S.H. Dalm (Virgil); P.L.A. van Daele (Paul); M.P. van Hagen (Martin); F.G.M. Kroese (Frans G.); J.A.G. van Roon (J. A G); A. Harkin (Andrew); A.W. Dik (Willem); H.A. Drexhage (Hemmo); E.W. Lubberts (Erik); M.A. Versnel (Marjan)

    2016-01-01

    textabstractIntroduction Indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme converting tryptophan (TRP) to kynurenine (KYN), is driven in part by type I/II IFNs. Naïve T cells are polarized into FoxP3+ regulatory T cells (Tregs) upon exposure to either IDO+ cells or KYN. Recent studies

  4. NRVS Studies of the Peroxide Shunt Intermediate in a Rieske Dioxygenase and Its Relation to the Native FesupII/supOinf2/infReaction

    Czech Academy of Sciences Publication Activity Database

    Sutherlin, K. D.; Rivard, B. S.; Böttger, L. H.; Liu, L. V.; Rogers, M. S.; Srnec, Martin; Park, K.; Yoda, Y.; Kitao, S.; Kobayashi, Y.; Saito, M.; Seto, M.; Hu, M.; Zhao, J.; Lipscomb, J. D.; Solomon, E. I.

    2018-01-01

    Roč. 140, č. 16 (2018), s. 5544-5559 ISSN 0002-7863 Institutional support: RVO:61388955 Keywords : NRVS studies * Rieske dioxygenase * mononuclear nonheme iron enzymes Subject RIV: CF - Physical ; The oretical Chemistry OBOR OECD: Physical chemistry Impact factor: 13.858, year: 2016

  5. Degradation of polychlorinated biphenyls using mesoporous iron-based spinels

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Linyan; Su, Guijin, E-mail: gjsu@rcees.ac.cn; Zhang, Aiqian; Shi, Yali; Xia, Chaobo; Lu, Huijie; Li, Liewu; Liu, Sha; Zheng, Minghui

    2013-10-15

    Highlights: • The NiFe{sub 2}O{sub 4} had the highest activity in degradation of CB-209, followed by Fe{sub 3}O{sub 4}. • Hydroxyl species, organic acids, PCBs and chlorobenzenes were identified as products. • Three degradation reactions and one combination reaction competitively occurred. • Hydrodechlorination of CB-209 was more favored over Fe{sub 3}O{sub 4} than NiFe{sub 2}O{sub 4}. • Oxidation reaction of CB-209 was more favored over NiFe{sub 2}O{sub 4} than Fe{sub 3}O{sub 4}. -- Abstract: A series of mesoporous iron-based spinel materials were synthesized to degrade polychlorinated biphenyls (PCBs), with CB-209 being used as a model compound. The materials were characterized by X-ray powder diffraction (XRD), pore structure analysis, and X-ray photoelectron spectroscopy (XPS). A comparison of the dechlorination efficiencies (DEs) of the materials revealed that NiFe{sub 2}O{sub 4} had the highest DE, followed by Fe{sub 3}O{sub 4}. Newly produced polychlorinated biphenyls, chlorinated benzenes, hydroxyl species and organic acids were detected by gas chromatography–mass spectrometry, high performance liquid chromatography–mass spectrometry and ion chromatograph. Identification of the intermediate products indicates that three degradation pathways, hydrodechlorination, the breakage of C-C bridge bond and oxidative reaction, accompanied by one combination reaction, are competitively occurring over the iron-based spinels. The relative amounts of produced three NoCB isomers were illustrated by the C-Cl BDEs of CB-209 at meta-, para- and ortho-positions, and their energy gap between HOMO and LUMO. The consumption of the reactive oxygen species caused by the transformation of Fe{sub 3}O{sub 4} into Fe{sub 2}O{sub 3} in the Fe{sub 3}O{sub 4} reaction system, and the existence of the highly reactive O{sub 2}{sup −}· species in the NiFe{sub 2}O{sub 4} reaction system, could provide a reason why the oxidation reaction was more favored over NiFe{sub 2}O

  6. Functional diversity of bacterial genes associated with aromatic hydrocarbon degradation in anthropogenic dark earth of Amazonia

    Directory of Open Access Journals (Sweden)

    Mariana Gomes Germano

    2012-05-01

    Full Text Available The objective of this work was to evaluate the catabolic gene diversity for the bacterial degradation of aromatic hydrocarbons in anthropogenic dark earth of Amazonia (ADE and their biochar (BC. Functional diversity analyses in ADE soils can provide information on how adaptive microorganisms may influence the fertility of soils and what is their involvement in biogeochemical cycles. For this, clone libraries containing the gene encoding for the alpha subunit of aromatic ring-hydroxylating dioxygenases (α-ARHD bacterial gene were constructed, totaling 800 clones. These libraries were prepared from samples of an ADE soil under two different land uses, located at the Caldeirão Experimental Station - secondary forest (SF and agriculture (AG -, and the biochar (SF_BC and AG_BC, respectively. Heterogeneity estimates indicated greater diversity in BC libraries; and Venn diagrams showed more unique operational protein clusters (OPC in the SF_BC library than the ADE soil, which indicates that specific metabolic processes may occur in biochar. Phylogenetic analysis showed unidentified dioxygenases in ADE soils. Libraries containing functional gene encoding for the alpha subunit of the aromatic ring-hydroxylating dioxygenases (ARHD gene from biochar show higher diversity indices than those of ADE under secondary forest and agriculture.

  7. The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

    NARCIS (Netherlands)

    Hoogenboom, Ron; Bovee, Toine; Traag, Win A; Hoogerbrugge, Ronald; Baumann, Bert; Portier, Liza; Weg, Guido van de; Vries, Jaap de

    2006-01-01

    The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a

  8. Polychlorinated biphenyls and their interaction with the environment

    Energy Technology Data Exchange (ETDEWEB)

    Dickerson, K.S.; Korte, N.E.

    1994-05-01

    This document is a review of the existing technical literature regarding the physical and biological properties of polychlorinated biphenyls (PCBs) and their interaction with the environment. It is intended to be used when evaluating PCB-contaminated soil and the effects of specific environmental conditions on PCB degradation. PCBs are a class of chlorinated aromatic compounds with 209 possible structural arrangements. The composition of PCBs in the environment changes over time due to various physiochemical and biological properties and processes: vapor pressure, solubility, octanol-water partitioning, adsorption, and biodegradation. As the number of chlorine atoms increases, both vapor pressure and water solubility decrease, while adsorption and the octanol-water partitioning coefficient increase. Dechlorination of PCBs occurs primarily through aerobic and anaerobic microbial degradation. Aerobic bacteria preferentially dechlorinate less-chlorinated PCBs, while anaerobic bacteria preferentially dechlorinate more highly chlorinated PCBs. The less-chlorinated PCB congeners are less persistent in the environment due to volatilization, solubility, and aerobic biodegradation, while the more-chlorinated PCBs are more persistent in the environment due to adsorption. The composition of an original PCB mixture in the environment can be expected to change due to a combination of processes described above. Any attempt to determine the source of PCBs or Aroclors identified in an environment sample must be approached with caution to avoid inaccurate conclusions.

  9. Preconception maternal polychlorinated biphenyl concentrations and the secondary sex ratio

    International Nuclear Information System (INIS)

    Taylor, Kira C.; Jackson, Leila W.; Lynch, Courtney D.; Kostyniak, Paul J.; Buck Louis, Germaine M.

    2007-01-01

    The secondary sex ratio is the ratio of male to female live births and historically has ranged from 102 to 106 males to 100 females. Temporal declines have been reported in many countries prompting authors to hypothesize an environmental etiology. Blood specimens were obtained from 99 women aged 24-34 prior to attempting pregnancy and quantified for 76 polychlorinated biphenyl (PCB) congeners using dual column gas chromatography with electron capture detection. Women were prospectively followed until pregnancy or 12 cycles of trying. The odds of a male birth for three PCB groupings (total, estrogenic, anti-estrogenic) controlling for maternal characteristics were estimated using logistic regression. Among the 50 women with live births and PCB data, 26 female and 24 male infants were born (ratio 0.92). After adjusting for age and body mass index, odds of a male birth were elevated among women in the second (OR=1.29) and third (OR=1.48) tertiles of estrogenic PCBs; odds (OR=0.70) were reduced among women in the highest tertile of anti-estrogenic PCBs. All confidence intervals included one. The direction of the odds ratios in this preliminary study varied by PCB groupings, supporting the need to study specific PCB patterns when assessing environmental influences on the secondary sex ratio

  10. Polychlorinated Biphenyls Water Pollution along the River Nile, Egypt

    Directory of Open Access Journals (Sweden)

    Ayman Mohamed Megahed

    2015-01-01

    Full Text Available Ten polychlorinated biphenyl (PCB congeners were determined in water samples collected along the River Nile using gas chromatography-electron capture detector (GC-ECD. PCB concentrations ranged from 14 to 20 μg/L, which were higher than those reported in previous studies, indicating serious PCB pollution in the River Nile. PCB congener profiles varied depending on the sampling sties. PCB-138 was the predominant congener accounting for more than 18% of total PCBs. The composition of PCB congeners in the water revealed that highly chlorinated PCB technical mixtures such as Aroclor 1254 was the main PCB production historically used in Egypt. An increasing trend in PCB levels from the upper stream to the Nile estuaries was observed. The calculated flux of PCBs indicated that 6.8 tons of PCBs is dumped into the Mediterranean Sea each year from the River Nile. The hazard quotients and carcinogenic risk caused by PCB pollution in the River Nile were above the acceptable level indicating that PCBs in the River Nile water pose adverse health effects for all age groups. Our findings revealed that PCBs possess a serious risk to the Egyptian population that depends mainly on the River Nile as a source of water. Thus, stricter legislation and regulatory controls should be applied to reduce the risk of PCBs in Egypt.

  11. Phytoremediation of soil contaminated with cadmium, copper and polychlorinated biphenyls.

    Science.gov (United States)

    Wu, Longhua; Li, Zhu; Han, Cunliang; Liu, Ling; Teng, Ying; Sun, Xianghui; Pan, Cheng; Huang, Yujuan; Luo, Yongming; Christie, Peter

    2012-07-01

    A pot experiment and afield trial were conducted to study the remediation of an aged field soil contaminated with cadmium, copper and polychlorinated biphenyls (PCBs) (7.67 +/- 0.51 mg kg(-1) Cd, 369 +/- 1 mg kg(-1) Cu in pot experiment; 8.46 +/- 0.31 mg kg(-1) Cd, 468 +/- 7 mg kg(-1) Cu, 323 +/- 12 microg kg(-1) PCBs for field experiment) under different cropping patterns. In the pot experiment Sedum plumbizincicola showed pronounced Cd phytoextraction. After two periods (14 months) of cropping the Cd removal rates in these two treatments were 52.2 +/- 12.0 and 56.1 +/- 9.1%, respectively. Total soil PCBs in unplanted control pots decreased from 323 +/- 11 to 49.3 +/- 6.6 microg kg(-1), but with no significant difference between treatments. The field microcosm experiment intercropping of three plant species reduced the yield of S. plumbizincicola, with a consequent decrease in soil Cd removal. S. plumbizincicola intercropped with E. splendens had the highest shoot Cd uptake (18.5 +/- 1.8 mg pot(-1)) after 6 months planting followed by intercropping with M. sativa (15.9 +/- 1.9 mg pot(-1)). Liming with S. plumbizincicola intercropped with M. sativa significantly promoted soil PCB degradation by 25.2%. Thus, adjustment of soil pH to 5.56 combined with intercropping with S. plumbizincicola and M. sativagave high removal rates of Cd, Cu, and PCBs.

  12. Sex effect on polychlorinated biphenyl concentrations in fish: a synthesis

    Science.gov (United States)

    Madenjian, C.P.

    2011-01-01

    Polychlorinated biphenyls (PCBs) accumulate in fish primarily via food intake, and therefore, PCBs serve as a chemical tracer for food consumption. Sex differences in PCB concentrations of fish have been attributed to the following three mechanisms: (i) females losing a substantial portion of their PCB body burden during spawning and consequently their PCB concentration is considerably reduced immediately after spawning; (ii) sex differences in habitat utilization leading to sex differences in the PCB concentrations of the prey; and (iii) sex differences in gross growth efficiency, which is defined as growth divided by the amount of food consumption needed to achieve that growth. Based on my analyses and synthesis, mechanisms (i) and (ii) operate in relatively few fish populations, but can lead to mature males having PCB concentrations two to three times higher than mature female PCB concentrations. In contrast, mechanism (iii) operates in all fish populations, but typically, mechanism (iii) results in relatively modest sex differences, with mature males only between 15 and 35% higher in PCB concentration than mature females. In summary, the study of sex differences in PCB concentrations of fish has led to insights into fish behaviour and fish physiology.

  13. Organochlorine pesticides and polychlorinated biphenyls in California sea lions

    Energy Technology Data Exchange (ETDEWEB)

    Kannan, K.; Kajiwara, N.; Le Boeuf, B.J.; Tanabe, S

    2004-10-01

    Concentrations of polychlorinated biphenyls (PCBs), DDTs, chlordanes, HCHs, hexachlorobenzene (HCB), dieldrin, heptachlor epoxide, tris(4-chlorophenyl)methane (TCPMe), and tris(4-chlorophenyl)methanol (TCPMOH) were measured in the blubber of California sea lions (Zalophus californianus) collected in 2000. DDTs were the most predominant contaminants, followed by PCBs, chlordanes, TCPMe, HCHs, TCPMOH, dieldrin, and heptachlor epoxide. Concentrations of PCBs and DDTs varied from a few {mu}g/g to several hundreds of {mu}g/g on a lipid weight basis. Concentrations of DDTs have declined by an order of magnitude over the last three decades in California sea lions; nevertheless, the measured concentrations of PCBs and DDTs in California sea lions are still some of the highest values reported for marine mammals in recent years. Concentrations of organochlorines were highly correlated with one another. Concentrations of PCBs and DDTs in the blubber of gray whale, humpback whale, northern elephant seal, and harbor seal, and in the adipose fat of sea otter, were lower than the levels found in California sea lions, and were in the range of a few to several {mu}g/g on a lipid weight basis.

  14. Prenatal exposure to polychlorinated biphenyls: a neuropsychologic analysis.

    Science.gov (United States)

    Boucher, Olivier; Muckle, Gina; Bastien, Célyne H

    2009-01-01

    A large body of literature documents the effects of prenatal exposure to polychlorinated biphenyls (PCBs) on cognitive development of children. Despite this fact, no integrative synthesis has been published yet to identify the cognitive functions that are particularly affected. Our aim is to review this literature in an attempt to identify the cognitive profile associated with prenatal PCB exposure. Studies were identified by searching the PubMed database for articles published before June 2008. We reviewed data from nine prospective longitudinal birth cohorts for different aspects of cognition. Associations between indicators of prenatal PCB exposure and performance on cognitive tasks reported in the selected studies are summarized and classified as general cognitive abilities, verbal or visual-spatial skills, memory, attention, and executive functions. The most consistent effects observed across studies are impaired executive functioning related to increased prenatal PCB exposure. Negative effects on processing speed, verbal abilities, and visual recognition memory are also reported by most studies. Converging results from different cohort studies in which exposure arises from different sources make it unlikely that co-exposure with another associated contaminant is responsible for the observed effects. Prenatal PCB exposure appears to be related to a relatively specific cognitive profile of impairments. Failure to assess functions that are specifically impaired may explain the absence of effects found in some studies. Our findings have implications in the selection of cognitive assessment methods in future studies.

  15. Polychlorinated Biphenyls Water Pollution along the River Nile, Egypt.

    Science.gov (United States)

    Megahed, Ayman Mohamed; Dahshan, Hesham; Abd-El-Kader, Mahdy A; Abd-Elall, Amr Mohamed Mohamed; Elbana, Mariam Hassan; Nabawy, Ehab; Mahmoud, Hend A

    2015-01-01

    Ten polychlorinated biphenyl (PCB) congeners were determined in water samples collected along the River Nile using gas chromatography-electron capture detector (GC-ECD). PCB concentrations ranged from 14 to 20 μg/L, which were higher than those reported in previous studies, indicating serious PCB pollution in the River Nile. PCB congener profiles varied depending on the sampling sties. PCB-138 was the predominant congener accounting for more than 18% of total PCBs. The composition of PCB congeners in the water revealed that highly chlorinated PCB technical mixtures such as Aroclor 1254 was the main PCB production historically used in Egypt. An increasing trend in PCB levels from the upper stream to the Nile estuaries was observed. The calculated flux of PCBs indicated that 6.8 tons of PCBs is dumped into the Mediterranean Sea each year from the River Nile. The hazard quotients and carcinogenic risk caused by PCB pollution in the River Nile were above the acceptable level indicating that PCBs in the River Nile water pose adverse health effects for all age groups. Our findings revealed that PCBs possess a serious risk to the Egyptian population that depends mainly on the River Nile as a source of water. Thus, stricter legislation and regulatory controls should be applied to reduce the risk of PCBs in Egypt.

  16. Binding properties of halogenated biphenyls to cells and macromolecules

    International Nuclear Information System (INIS)

    Pepe, M.G.

    1982-01-01

    The interaction of polychlorinated biphenyls (PCB) with serum proteins may help explain the cellular incorporation of PCB as the effect of PCB on thyroid hormone function. PCB reduces serum thyroxine and triiodothyronine levels in rats; the mechanism for this effect is unknown. The initial distribution of PCB from blood to tissue is rapid and depends on blood perfusion and tissue affinity; however, the translocation of unmetabolized PCB from its initial storage sites to adipose tissue may depend on serum and cellular protein interactions. Therefore, the ability of PCB to displace triiodothyronine binding to albumin and antibodies, as well as the effect of binding to serum proteins as a mechanism for cellular incorporation was measured. PCB binding to albumin showed both high and low affinity binding sites. This binding was able to prevent triiodothyronine binding to albumin. The distribution of PCB inserum showed that lipoproteins contained 94% of the total 14 C PCB added, while 5% of the 14 C PCB was bound to albumin. The in vitro binding of 14 C PCB to serum obtained from rats pretreated with PCB in their diets for 6 months showed a significant decrease (p 14 C PCB was higher (p < 0.05) in liver, adrenal and adipose cells than pituitary and thyroid cells

  17. Remediation of PCB [polychlorinated biphenyl] -contaminated soils from scrapyards

    International Nuclear Information System (INIS)

    MacKnight, S.

    1991-01-01

    Much of the recent attention on contamination of the environment by polychlorinated biphenyls (PCB) has focused on liquid PCB spills from electrical equipment. A new, and possibly more serious, source of PCB contamination is the scrap yard, typically located in or near major urban centers, where the local scrap dealer would purchase used transformers or other PCB-containing electrical equipment, recover copper and other metals, and dump the PCB-containing oils on the ground. With the rising value of urban and suburban lands, these scrap yards may be slated for redevelopment, making the cleanup of contaminated soils necessary. The heterogeneous distribution of scrap yard contaminants requires a very detailed site assessment, and the heterogeneous mixture of typical scrap yard contaminants (not only PCB) cannot be treated in a simple fashion. These problems are illustrated for the case of the assessment and cleanup of a scrap yard site in Nova Scotia. A grid block system was used to sample soil at the site, and samples were analyzed for PCB, metals, and hydrocarbons. The most severely contaminated spots were mapped; groundwater patterns were also examined. The remediation process can be divided into 5 phases: physical separation of uncontaminated material; three stages of separation of materials into those having single, several-but-similar, and multicomponent mixed contaminations; and selection of appropriate process technologies. Since there is currently no approved PCB destruction facility in Atlantic Canada, excavated soils containing PCB are stored securely on the site to await approval for some type of incineration process

  18. Organochlorine pesticides and polychlorinated biphenyls in California sea lions

    International Nuclear Information System (INIS)

    Kannan, K.; Kajiwara, N.; Le Boeuf, B.J.; Tanabe, S.

    2004-01-01

    Concentrations of polychlorinated biphenyls (PCBs), DDTs, chlordanes, HCHs, hexachlorobenzene (HCB), dieldrin, heptachlor epoxide, tris(4-chlorophenyl)methane (TCPMe), and tris(4-chlorophenyl)methanol (TCPMOH) were measured in the blubber of California sea lions (Zalophus californianus) collected in 2000. DDTs were the most predominant contaminants, followed by PCBs, chlordanes, TCPMe, HCHs, TCPMOH, dieldrin, and heptachlor epoxide. Concentrations of PCBs and DDTs varied from a few μg/g to several hundreds of μg/g on a lipid weight basis. Concentrations of DDTs have declined by an order of magnitude over the last three decades in California sea lions; nevertheless, the measured concentrations of PCBs and DDTs in California sea lions are still some of the highest values reported for marine mammals in recent years. Concentrations of organochlorines were highly correlated with one another. Concentrations of PCBs and DDTs in the blubber of gray whale, humpback whale, northern elephant seal, and harbor seal, and in the adipose fat of sea otter, were lower than the levels found in California sea lions, and were in the range of a few to several μg/g on a lipid weight basis

  19. Activated carbon immobilizes residual polychlorinated biphenyls in weathered contaminated soil.

    Science.gov (United States)

    Langlois, Valérie S; Rutter, Allison; Zeeb, Barbara A

    2011-01-01

    Activated carbon (AC) has recently been shown to be effective in sequestering persistent organic pollutants (POPs) from aquatic sediments. Most studies have demonstrated significant reductions of POP concentrations in water and in aquatic organisms; however, limited data exist on the possibility of using AC to immobilize remaining POPs at terrestrial contaminated sites. Under greenhouse conditions, pumpkin ssp cv. Howden) were grown, and red wiggler worms () were exposed to an industrial contaminated soil containing a mixture of polychlorinated biphenyls (PCBs), i.e., Aroclors 1254 and 1260) treated with one of four concentrations of AC (0.2, 0.8, 3.1, and 12.5%) for 2 mo. The addition of AC to contaminated soils virtually eliminated the bioavailability of PCBs to the plant and invertebrate species. There were reductions in PCB concentrations of more than 67% in ssp and 95% in . These data suggest that AC could be included as part of comprehensive site closure strategy at PCB-contaminated sites. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  20. The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond.

    Science.gov (United States)

    Fedeles, Bogdan I; Singh, Vipender; Delaney, James C; Li, Deyu; Essigmann, John M

    2015-08-21

    The AlkB family of Fe(II)- and α-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation. The prototypical and homonymous family member is an Escherichia coli "adaptive response" protein that protects the bacterial genome against alkylation damage. AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. Nine mammalian AlkB homologs exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes. This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. A Refined Model for the Structure of Acireductone Dioxygenase from Klebsiella ATCC 8724 Incorporating Residual Dipolar Couplings

    Energy Technology Data Exchange (ETDEWEB)

    Pochapsky, Thomas C., E-mail: pochapsk@brandeis.edu; Pochapsky, Susan S.; Ju Tingting [Brandeis University, Department of Chemistry (United States); Hoefler, Chris [Brandeis University, Department of Biochemistry (United States); Liang Jue [Brandeis University, Department of Chemistry (United States)

    2006-02-15

    Acireductone dioxygenase (ARD) from Klebsiella ATCC 8724 is a metalloenzyme that is capable of catalyzing different reactions with the same substrates (acireductone and O{sub 2}) depending upon the metal bound in the active site. A model for the solution structure of the paramagnetic Ni{sup 2+}-containing ARD has been refined using residual dipolar couplings (RDCs) measured in two media. Additional dihedral restraints based on chemical shift (TALOS) were included in the refinement, and backbone structure in the vicinity of the active site was modeled from a crystallographic structure of the mouse homolog of ARD. The incorporation of residual dipolar couplings into the structural refinement alters the relative orientations of several structural features significantly, and improves local secondary structure determination. Comparisons between the solution structures obtained with and without RDCs are made, and structural similarities and differences between mouse and bacterial enzymes are described. Finally, the biological significance of these differences is considered.

  2. Structure and mechanism leading to formation of the cysteine sulfinate product complex of a biomimetic cysteine dioxygenase model.

    Science.gov (United States)

    Sallmann, Madleen; Kumar, Suresh; Chernev, Petko; Nehrkorn, Joscha; Schnegg, Alexander; Kumar, Devesh; Dau, Holger; Limberg, Christian; de Visser, Sam P

    2015-05-11

    Cysteine dioxygenase is a unique nonheme iron enzyme that is involved in the metabolism of cysteine in the body. It contains an iron active site with an unusual 3-His ligation to the protein, which contrasts with the structural features of common nonheme iron dioxygenases. Recently, some of us reported a truly biomimetic model for this enzyme, namely a trispyrazolylborato iron(II) cysteinato complex, which not only has a structure very similar to the enzyme-substrate complex but also represents a functional model: Treatment of the model with dioxygen leads to cysteine dioxygenation, as shown by isolating the cysteine part of the product in the course of the work-up. However, little is known on the conversion mechanism and, so far, not even the structure of the actual product complex had been characterised, which is also unknown in case of the enzyme. In a multidisciplinary approach including density functional theory calculations and X-ray absorption spectroscopy, we have now determined the structure of the actual sulfinato complex for the first time. The Cys-SO2 (-) functional group was found to be bound in an η(2) -O,O-coordination mode, which, based on the excellent resemblance between model and enzyme, also provides the first support for a corresponding binding mode within the enzymatic product complex. Indeed, this is again confirmed by theory, which had predicted a η(2) -O,O-binding mode for synthetic as well as the natural enzyme. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Isolation and characterization of a novel polychlorinated biphenyl-degrading bacterium, Paenibacillus sp. KBC101

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, M.; Ezaki, S.; Suzuki, N.; Kurane, R. [Kubota Corporation, Ryuugasaki City (Japan). Biotechnology Research Centre

    2005-07-01

    The biphenyl-utilizing bacterial strain KBC101 has been newly isolated from soil. Biphenyl-grown cells of KBC101 efficiently degraded di- to nonachlorobiphenyls. The isolate was identified as Paenibacillus sp. with respect to its 16S rDNA sequence and fatty acid profiles, as well as various biological and physiological characteristics. In the case of highly chlorinated biphenyl (polychlorinated biphenyl; PCB) congeners, the degradation activities of this strain were superior to those of the previously reported strong PCB degrader, Rhodococcus sp. RHA1. Recalcitrant coplanar PCBs, such as 3,4,3',4'-CB, were also efficiently degraded by strain KBC101 cells. This is the first report of a representative of the genus Paenibacillus capable of degrading PCBs. In addition to growth of biphenyl, strain KBC101 could grow on dibenzofuran, xanthene, benzophenone, anthrone, phenanthrene, napthalene, fluorene, fluoranthene, and chrysene as sole sources of carbon and energy. Paenibacillus sp. strain KBC101 presented heterogeneous degradation profiles toward various aromatic compounds. (orig.)

  4. Polychlorinated biphenyls in Spanish adults: Determinants of serum concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Agudo, Antonio, E-mail: a.agudo@iconcologia.net [Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, Av. Gran Via no 199-203, 08907 L' Hospitalet de Llobregat (Spain); Goni, Fernando [Laboratorio de Salud Publica de Guipuzcoa, 20013 San Sebastian (Spain); CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Etxeandia, Arsenio [Laboratorio de Salud Publica de Vizcaya, 48010 Bilbao (Spain); Vives, Asuncion [Laboratorio Unificado Donostia, Hospital N. S. Aranzazu, 20014 San Sebastian (Spain); Millan, Esmeralda [Departamento de Quimica Aplicada, Universidad del Pais Vasco, Facultad de Quimica, 20080 San Sebastian (Spain); Lopez, Raul [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Amiano, Pilar [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Direccion de Salud de Guipuzcoa, 20013 San Sebastian (Spain); Ardanaz, Eva; Barricarte, Aurelio [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Instituto de Salud Publica de Navarra, 31003 Pamplona (Spain); Dolores Chirlaque, M. [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Consejeria de Sanidad, 3008 Murcia (Spain); Dorronsoro, Miren [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Direccion de Salud de Guipuzcoa, 20013 San Sebastian (Spain); Jakszyn, Paula [Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, Av. Gran Via no 199-203, 08907 L' Hospitalet de Llobregat (Spain); Larranaga, Nerea [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Direccion de Salud de Guipuzcoa, 20013 San Sebastian (Spain); Martinez, Carmen [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Escuela Andaluza de Salud Publica, 18080 Granada (Spain); Navarro, Carmen [CIBER Epidemiologia y Salud Publica (CIBERESP) (Spain); Consejeria de Sanidad, 3008 Murcia (Spain); Rodriguez, Laudina [Consejeria de Salud y Servicios Sanitarios de Asturias, 33001 Oviedo (Spain); and others

    2009-07-15

    Background: Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population. Objective: To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations. Methods: Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD). Results: The concentration of total PCBs was 459 ng/g lipids (or 3.1 {mu}g/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 {mu}g/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately. Conclusions: We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.

  5. Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

    Science.gov (United States)

    Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

    2012-10-01

    Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies

  6. Association between polychlorinated biphenyls and Parkinson’s disease neuropathology

    Science.gov (United States)

    Hatcher-Martin, Jaime M.; Gearing, Marla; Steenland, Kyle; Levey, Allan I.; Miller, Gary W.; Pennell, Kurt D.

    2012-01-01

    Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and

  7. Immunotoxicity Monitoring in a Population Exposed to Polychlorinated Biphenyls

    Directory of Open Access Journals (Sweden)

    Hajo Haase

    2016-03-01

    Full Text Available The relationship between polychlorinated biphenyl (PCB burden and several indicators of immune function was investigated as part of the HELPcB (Health Effects in High-Level Exposure to PCB program, offering bio-monitoring to workers, relatives, and neighbors exposed to PCBs by a German transformers and capacitors recycling company. The present retrospective observational study evaluates the correlation of plasma levels of total PCBs, five indicator congeners (28, 101, 138, 153, 180, and seven dioxin-like congeners (105, 114, 118, 156, 157, 167, 189 with several parameters of immune function. The cross-sectional study was performed immediately after the end of exposure (258 subjects, and one (218 subjects, and two (177 subjects years later. At the first time point, measurements showed significant positive correlation between congeners with low to medium chlorination and the relative proportion of CD19 positive B-cells among lymphocytes, as well as a negative correlation of PCB114 with serum IgM, and of PCB 28 with suppressor T-cell and NK-cell numbers. Congeners with a high degree of chlorination, in particular PCB157 and 189, were positively associated with expression of the activation marker CD25 on T-cells in the cohort of the second time point. No associations between PCB levels and IFN-y production by T-cells and killing by NK-cells were found. In conclusion, there were several effects on the cellular composition of adaptive immunity, affecting both T- and B-cells. However, the values were not generally outside the reference ranges for healthy adult individuals and did not indicate overt functional immunodeficiency, even in subjects with the uppermost PCB burden.

  8. Polychlorinated biphenyls in Spanish adults: Determinants of serum concentrations

    International Nuclear Information System (INIS)

    Agudo, Antonio; Goni, Fernando; Etxeandia, Arsenio; Vives, Asuncion; Millan, Esmeralda; Lopez, Raul; Amiano, Pilar; Ardanaz, Eva; Barricarte, Aurelio; Dolores Chirlaque, M.; Dorronsoro, Miren; Jakszyn, Paula; Larranaga, Nerea; Martinez, Carmen; Navarro, Carmen; Rodriguez, Laudina

    2009-01-01

    Background: Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population. Objective: To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations. Methods: Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD). Results: The concentration of total PCBs was 459 ng/g lipids (or 3.1 μg/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 μg/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately. Conclusions: We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.

  9. Dechlorination of polychlorinated biphenyls by iron and its oxides.

    Science.gov (United States)

    Sun, Yifei; Liu, Xiaoyuan; Kainuma, Masashi; Wang, Wei; Takaoka, Masaki; Takeda, Nobuo

    2015-10-01

    The decomposition efficiency of polychlorinated biphenyls (PCBs) was determined using elemental iron (Fe) and three iron (hydr)oxides, i.e., α-Fe2O3, Fe3O4, and α-FeOOH, as catalysts. The experiments were performed using four distinct PCB congeners (PCB-209, PCB-153, and the coplanar PCB-167 and PCB-77) at temperatures ranging from 180 °C to 380 °C and under an inert, oxidizing or reducing atmosphere composed of N2, N2+O2, or N2+H2. From these three options N2 showed to provide the best reaction atmosphere. Among the iron compounds tested, Fe3O4 showed the highest activity for decomposing PCBs. The decomposition efficiencies of PCB-209, PCB-167, PCB-153, and PCB-77 by Fe3O4 in an N2 atmosphere at 230 °C were 88.5%, 82.5%, 69.9%, and 66.4%, respectively. Other inorganic chlorine (Cl) products which were measured by the amount of inorganic Cl ions represented 82.5% and 76.1% of the reaction products, showing that ring cleavage of PCBs was the main elimination process. Moreover, the dechlorination did not require a particular hydrogen donor. We used X-ray photoelectron spectroscopy to analyze the elemental distribution at the catalyst's surface. The O/Fe ratio influenced upon the decomposition efficiency of PCBs: the lower this ratio, the higher the decomposition efficiency. X-ray absorption near edge structure spectra showed that α-Fe2O3 effectively worked as a catalyst, while Fe3O4 and α-FeOOH were consumed as reactants, as their final state is different from their initial state. Finally, a decomposition pathway was postulated in which the Cl atoms in ortho-positions were more difficult to eliminate than those in the para- or meta-positions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Mol, Nanette M; Sørensen, Nicolina; Weihe, Pal

    2002-01-01

    To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty.......To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty....

  11. Molecular Descriptors Family on Structure Activity Relationships 6. Octanol-Water Partition Coefficient of Polychlorinated Biphenyls

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2006-01-01

    Full Text Available Octanol-water partition coefficient of two hundred and six polychlorinated biphenyls was model by the use of an original method based on complex information obtained from compounds structure. The regression analysis shows that best results are obtained in four-varied model (r2 = 0.9168. The prediction ability of the model was studied through leave-one-out analysis (r2cv(loo = 0.9093 and in training and test sets analysis. Modeling the octanol-water partition coefficient of polychlorinated biphenyls by integration of complex structural information provide a stable and performing four-varied model, allowing us to make remarks about relationship between structure of polychlorinated biphenyls and associated octanol-water partition coefficients.

  12. Toward a generalized computational workflow for exploiting transient pockets as new targets for small molecule stabilizers: Application to the homogentisate 1,2-dioxygenase mutants at the base of rare disease Alkaptonuria.

    Science.gov (United States)

    Bernini, Andrea; Galderisi, Silvia; Spiga, Ottavia; Bernardini, Giulia; Niccolai, Neri; Manetti, Fabrizio; Santucci, Annalisa

    2017-10-01

    Alkaptonuria (AKU) is an inborn error of metabolism where mutation of homogentisate 1,2-dioxygenase (HGD) gene leads to a deleterious or misfolded product with subsequent loss of enzymatic degradation of homogentisic acid (HGA) whose accumulation in tissues causes ochronosis and degeneration. There is no licensed therapy for AKU. Many missense mutations have been individuated as responsible for quaternary structure disruption of the native hexameric HGD. A new approach to the treatment of AKU is here proposed aiming to totally or partially rescue enzyme activity by targeting of HGD with pharmacological chaperones, i.e. small molecules helping structural stability. Co-factor pockets from oligomeric proteins have already been successfully exploited as targets for such a strategy, but no similar sites are present at HGD surface; hence, transient pockets are here proposed as a target for pharmacological chaperones. Transient pockets are detected along the molecular dynamics trajectory of the protein and filtered down to a set of suitable sites for structural stabilization by mean of biochemical and pharmacological criteria. The result is a computational workflow relevant to other inborn errors of metabolism requiring rescue of oligomeric, misfolded enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

    OpenAIRE

    Curti, A; Trabanelli, S; Onofri, C; Aluigi, M; Salvestrini, V; Ocadlikova, D; Evangelisti, C; Rutella, S; De Cristofaro, R; Ottaviani, E; Baccarani, M; Lemoli, RM

    2010-01-01

    Background: The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia.\\ud Design and Methods: Leukemic d...

  14. Remarkable Role of Indoleamine 2,3-Dioxygenase and Tryptophan Metabolites in Infectious Diseases: Potential Role in Macrophage-Mediated Inflammatory Diseases

    OpenAIRE

    Murakami, Yuki; Hoshi, Masato; Imamura, Yukio; Arioka, Yuko; Yamamoto, Yasuko; Saito, Kuniaki

    2013-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1), the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and th...

  15. Crystallization and preliminary crystallographic analysis of maganese(II)-dependent 2,3-dihydroxybiphenyl 1,2-dioxygenase from Bacillus sp. JF8

    International Nuclear Information System (INIS)

    Senda, Miki; Hatta, Takashi; Kimbara, Kazuhide; Senda, Toshiya

    2010-01-01

    A thermostable manganese(II)-dependent 2,3-dihydroxybiphenyl-1,2-dioxygenase derived from Bacillus sp. JF8 was crystallized in two forms using the sitting-drop vapour-diffusion method. Both crystals diffracted to approximately 1.3 Å resolution. A thermostable manganese(II)-dependent 2,3-dihydroxybiphenyl-1,2-dioxygenase derived from Bacillus sp. JF8 was crystallized. The initial screening for crystallization was performed by the sitting-drop vapour-diffusion method using a crystallization robot, resulting in the growth of two crystal forms. The first crystal belonged to space group P1, with unit-cell parameters a = 62.7, b = 71.4, c = 93.6 Å, α = 71.2, β = 81.0, γ = 64.0°, and diffracted to 1.3 Å resolution. The second crystal belonged to space group I222, with unit-cell parameters a = 74.2, b = 90.8, c = 104.3 Å, and diffracted to 1.3 Å resolution. Molecular-replacement trials using homoprotocatechuate 2,3-dioxygenase from Arthrobacter globiformis (28% amino-acid sequence identity) as a search model provided a satisfactory solution for both crystal forms

  16. Foetal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice

    International Nuclear Information System (INIS)

    Darnerud, P.O.; Sinjari, T.; Joensson, C.J.

    1996-01-01

    Earlier studies have shown that the Ah-receptor binding polychlorinated biphenyl (PCB) congener 3,3',4,4'-tetrachlorobiphenyl (IUPAC number CB-77) accumulated as hydroxy and methylsulphone metabolites in late gestational mice foetuses. In the present paper the foetal accumulation potential in mice of other dioxin-like PCB congeners was studied: 3,3'4,4',4-pentachlorobiphenyl, 3,3'4,4'5,5'-hexachlorobiphenyl and 2,3,3',4,4'-pentachlorobiphenyl (IUPAC numbers CB-126, CB-169, CB-105, to some extent dioxin-like) were compared to results of CB-77 (all congeners 14 C-labelled and in equimolar doses (2.0 μmol/kg body wt.)). CB-77 resulted in the comparatively strongest foetal 14 C-accumulation, when measured in plasma or whole body homogenate four days after administration (day 17 of pregnancy); the plasma 14 C-values (calculated as pmol/g wet wt.) were 760, 130, 60 and 40 for CB-77, -126, 105 and -169, respectively, and the CB-77 derived radioactivity in the foetal compartment was 3.6% of administered dose (i.e. a considerable portion of the remaining maternal body radioactivity). Thin-layer chromatography (TLC) results, suggesting extensive CB-77 metabolism and foetal metabolite uptake, support earlier findings. The effects of CB-77 and CB-169 on foetal 7-ethoxyresorufin-O-deethylase (EROD) activities (day 17 of gestation; two days after 5 mg/kg body wt. dose (14.0-17.0 μmol/kg body wt.)) was about 20 times lower than of CB-126. In the dam, high radioactivity levels were observed int he liver and fat (highest concentrations found in CB-126 and CB-105, respectively). Strain comparison - foetal 14 C-uptake (four days after administration of CB-77) in C57BL mice was almost five times higher than in NMRI - may be correlated to earlier observed differences in EROD activities between these strains. The present results indicate that congener and strain differences exist regarding both foetal and maternal distribution patterns of coplanar PCB congeners and point out the

  17. Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women

    International Nuclear Information System (INIS)

    Spector, June T.; De Roos, Anneclaire J.; Ulrich, Cornelia M.; Sheppard, Lianne; Sjoedin, Andreas; Wener, Mark H.; Wood, Brent

    2014-01-01

    Background: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. Objectives: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. Methods: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. Results: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. Conclusions: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. - Highlights: • Plasma PCBs and immune function were measured in 109 women at baseline and one year. • Immune measures included T lymphocyte proliferation

  18. Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Spector, June T., E-mail: spectj@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105 (United States); Department of Medicine, School of Medicine, University of Washington, Seattle, WA (United States); De Roos, Anneclaire J., E-mail: ajd335@drexel.edu [Epidemiology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, Seattle, WA 98109 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Ulrich, Cornelia M., E-mail: neli.ulrich@nct-heidelberg.de [Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, Seattle, WA 98109 (United States); National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Sheppard, Lianne, E-mail: sheppard@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105 (United States); Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA (United States); Sjoedin, Andreas, E-mail: asjodin@cdc.gov [National Center for Environmental Health, CDC, 4770 Buford Highway NE, Atlanta, GA 30341 (United States); Wener, Mark H., E-mail: wener@u.washington.edu [Department of Medicine, School of Medicine, University of Washington, Seattle, WA (United States); Wood, Brent, E-mail: woodbl@u.washington.edu [Department of Medicine, School of Medicine, University of Washington, Seattle, WA (United States); and others

    2014-05-01

    Background: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. Objectives: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. Methods: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. Results: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. Conclusions: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. - Highlights: • Plasma PCBs and immune function were measured in 109 women at baseline and one year. • Immune measures included T lymphocyte proliferation

  19. Lactational transfer of mercury and polychlorinated biphenyls in polar bears.

    Science.gov (United States)

    Knott, Katrina K; Boyd, Daryle; Ylitalo, Gina M; O'Hara, Todd M

    2012-07-01

    We examined concentrations of total mercury (tHg, inorganic and methylated forms) and polychlorinated biphenyls (PCBs) in blood and milk from free-ranging Southern Beaufort-Chukchi Sea polar bears (Ursus maritimus) to assess maternal transfer of contaminants during lactation and the potential health risk to nursing young. Concentrations of contaminants in the blood of dependent and juvenile animals (ages 1-5 years) ranged from 35.9 to 52.2 μg kg(-1) ww for tHg and 13.9 to 52.2 μg kg(-1) ww (3255.81-11067.79 μg kg(-1) lw) for ΣPCB(7)s, similar to those of adult females, but greater than adult males. Contaminant concentrations in milk ranged from 5.7 to 71.8 μg tHg kg(-1)ww and 160 to 690 μg ΣPCB(11)s kg(-1) ww (547-5190 μg kg(-1) lw). The daily intake levels for tHg by milk consumption estimated for dependent young were below the tolerable daily intake level (TDIL) of tHg established for adult humans. Although the daily intake levels of PCBs through milk consumption for cubs of the year exceeded the TDIL thresholds, calculated dioxin equivalents for PCBs in milk were below adverse physiological thresholds for aquatic mammals. Relatively high concentrations of non-dioxin like PCBs in polar bear milk and blood could impact endocrine function of Southern Beaufort-Chukchi Sea polar bears, but this is uncertain. Transfer of contaminants during mid to late lactation likely limits bioaccumulation of dietary contaminants in female polar bears during spring. As polar bears respond to changes in their arctic sea ice habitat, the adverse health impacts associated with nutritional stress may be exacerbated by tHg and PCBs exposure, especially in ecologically and toxicologically sensitive polar bear cohorts such as reproductive females and young. Copyright © 2012. Published by Elsevier Ltd.

  20. CAR gene cluster and transcript levels of carotenogenic genes in Rhodotorula mucilaginosa.

    Science.gov (United States)

    Landolfo, Sara; Ianiri, Giuseppe; Camiolo, Salvatore; Porceddu, Andrea; Mulas, Giuliana; Chessa, Rossella; Zara, Giacomo; Mannazzu, Ilaria

    2018-01-01

    A molecular approach was applied to the study of the carotenoid biosynthetic pathway of Rhodotorula mucilaginosa. At first, functional annotation of the genome of R. mucilaginosa C2.5t1 was carried out and gene ontology categories were assigned to 4033 predicted proteins. Then, a set of genes involved in different steps of carotenogenesis was identified and those coding for phytoene desaturase, phytoene synthase/lycopene cyclase and carotenoid dioxygenase (CAR genes) proved to be clustered within a region of ~10 kb. Quantitative PCR of the genes involved in carotenoid biosynthesis showed that genes coding for 3-hydroxy-3-methylglutharyl-CoA reductase and mevalonate kinase are induced during exponential phase while no clear trend of induction was observed for phytoene synthase/lycopene cyclase and phytoene dehydrogenase encoding genes. Thus, in R. mucilaginosa the induction of genes involved in the early steps of carotenoid biosynthesis is transient and accompanies the onset of carotenoid production, while that of CAR genes does not correlate with the amount of carotenoids produced. The transcript levels of genes coding for carotenoid dioxygenase, superoxide dismutase and catalase A increased during the accumulation of carotenoids, thus suggesting the activation of a mechanism aimed at the protection of cell structures from oxidative stress during carotenoid biosynthesis. The data presented herein, besides being suitable for the elucidation of the mechanisms that underlie carotenoid biosynthesis, will contribute to boosting the biotechnological potential of this yeast by improving the outcome of further research efforts aimed at also exploring other features of interest.

  1. Chemometric comparison of polychlorinated biphenyl residues and toxicologically active polychlorinated biphenyl congeners in the eggs of Forster's Terns (Sterna fosteri)

    Science.gov (United States)

    Schwartz, Ted R.; Stalling, David L.

    1991-01-01

    The separation and characterization of complex mixtures of polychlorinated biphenyls (PCBs) is approached from the perspective of a problem in chemometrics. A technique for quantitative determination of PCB congeners is described as well as an enrichment technique designed to isolate only those congener residues which induce mixed aryl hydrocarbon hydroxylase enzyme activity. A congener-specific procedure is utilized for the determination of PCBs in whichn-alkyl trichloroacetates are used as retention index marker compounds. Retention indices are reproducible in the range of ±0.05 to ±0.7 depending on the specific congener. A laboratory data base system developed to aid in the editing and quantitation of data generated from capillary gas chromatography was employed to quantitate chromatographic data. Data base management was provided by computer programs written in VAX-DSM (Digital Standard MUMPS) for the VAX-DEC (Digital Equipment Corp.) family of computers.In the chemometric evaluation of these complex chromatographic profiles, data are viewed from a single analysis as a point in multi-dimensional space. Principal Components Analysis was used to obtain a representation of the data in a lower dimensional space. Two-and three-dimensional proections based on sample scores from the principal components models were used to visualize the behavior of Aroclor® mixtures. These models can be used to determine if new sample profiles may be represented by Aroclor profiles. Concentrations of individual congeners of a given chlorine substitution may be summed to form homologue concentration. However, the use of homologue concentrations in classification studies with environmental samples can lead to erroneous conclusions about sample similarity. Chemometric applications are discussed for evaluation of Aroclor mixture analysis and compositional description of environmental residues of PCBs in eggs of Forster's terns (Sterna fosteri) collected from colonies near Lake Poygan

  2. Neurological condition in 18-month-old children perinatally exposed to polychlorinated biphenyls and dioxins

    NARCIS (Netherlands)

    Huisman, M; KoopmanEsseboom, C; vanderPaauw, CG; Tuinstra, LGMT; Fidler, [No Value; WeisglasKuperus, N; Sauer, PJJ; Boersma, ER; Touwen, BCL

    1995-01-01

    The neurological optimality of 418 Dutch children was evaluated at the age of 18 months, in order to determine whether prenatal and breast milk mediated exposure to polychlorinated biphenyls (PCBs) and dioxins affected neurological development, Half of the infants were breast-fed, the other half

  3. Polychlorinated biphenyl-induced alterations of thyroid hormone homeostasis and brain development in the rat

    NARCIS (Netherlands)

    Morse, D.C.

    1995-01-01

    Introduction

    The work described in this thesis was undertaken to gain insight in the processes involved in the developmental neurotoxicity of polychlorinated biphenyls. It has been previously hypothesized that the alteration of thyroid hormone status by PCBs may

  4. EFFECTS OF POLYCHLORINATED-BIPHENYLS (PCBS) AND DIOXINS ON GROWTH AND DEVELOPMENT

    NARCIS (Netherlands)

    SAUER, PJJ; HUISMAN, M; KOOPMANESSEBOOM, C; MORSE, DC; SMITSVANPROOIJE, AE; VANDEBERG, KJ; TUINSTRA, LGMT; VANDERPAAUW, CG; BOERSMA, ER; WEISGLASKUPERUS, N; LAMMERS, JHCM; KULIG, BM; BROUWER, A

    1994-01-01

    Polychlorinated biphenyls (PCBs) and dioxins are potentially toxic compounds which occur widely in the environment. Their effects on the growth and development of infants at the levels currently found in highly industrialised western countries is not well known. This Dutch multicenter study,

  5. Preparation of plants containing bacterial enzyme for degradation of polychlorinated biphenyls

    Czech Academy of Sciences Publication Activity Database

    Francová, K.; Surá, M.; Macek, Tomáš; Szekeres, M.; Bancos, S.; Demnerová, K.; Sylvestre, M.; Macková, M.

    2003-01-01

    Roč. 12, č. 3 (2003), s. 309-313 ISSN 1018-4619 Institutional research plan: CEZ:AV0Z4055905 Keywords : transgenic plants * polychlorinated biphenyls * phytoremediation Subject RIV: DK - Soil Contamination ; De-contamination incl. Pesticides Impact factor: 0.325, year: 2003

  6. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos.

  7. New Biochemical Pathway for Biphenyl Degradation in Plants: Structural, Mechanistic and Biotechnological Aspects

    International Nuclear Information System (INIS)

    Pacios, L. F.; Campos, V. M.; Merino, I.; Gomez, L.

    2009-01-01

    Polychlorinated biphenyls (PVBs) and other structurally-related xenobiotics are amongst the most relevant organic pollutants known today. while some bacterial species can metabolize PCBs, with varying efficiency, no catabolic pathways have yet been described in plants. This is so despite the great potential of (at least some) plant species for soil and groundwater decontamination, a technology known as phyto remediation. (Author)

  8. Predicting the bioaccumulation of polyaromatic hydrocarbons and polychlorinated biphenyls in benthic animals in sediments

    NARCIS (Netherlands)

    Tuikka, A. I.; Leppänen, M. T.; Akkanen, J.; Sormunen, A. J.; Leonards, P. E.G.; van Hattum, B.; van Vliet, L. A.; Brack, W.; Smedes, F.; Kukkonen, J. V.K.

    2016-01-01

    There were two main objectives in this study. The first was to compare the accuracy of different prediction methods for the chemical concentrations of polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the organism, based on the measured chemical concentrations existing in

  9. Effects of black carbon on bioturbination-induced benthic fluxes of polychlorinated biphenyls

    NARCIS (Netherlands)

    Koelmans, A.A.; Jonker, M.T.O.

    2011-01-01

    It is unknown whether carbonaceous geosorbents, such as black carbon (BC) affect bioturbation by benthic invertebrates, thereby possibly affecting sediment–water exchange of sediment-bound contaminants. Here, we assess the effects of oil soot on polychlorinated biphenyl (PCB) mass transfer from

  10. Contamination of free-range chicken eggs with dioxins and dioxin-like polychlorinated biphenyls

    NARCIS (Netherlands)

    Schoeters, G.; Hoogenboom, L.A.P.

    2006-01-01

    Dioxins and dioxin-like (DL) polychlorinated biphenyls (PCB) are persistent organic pollutants that enter the body mainly by food intake. A small margin exists between current exposure levels in the human population and the levels causing biological effects. Therefore, stringent control of

  11. Induction of monooxygenation in rainbow trout by polybrominated biphenyls: a comparative study.

    Science.gov (United States)

    Elcombe, C R; Lech, J J

    1978-01-01

    Two commercial polychlorinated biphenyl mixtures (Aroclor 1254 and Aroclor 1242) and one polybrominated biphenyl mixture (FireMaster BP-6) were examined for their abilities to induce hepatic microsomal monooxygenation in rainbow trout (Salmo gairdneri). Pretreatment of rainbow trout with Aroclors 1254 and 1242 (150 mg/kg IP) resulted in an approximate 10-fold induction of arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation within 7 days after injection. These enzyme activities remained elevated above control values for at least 2-3 weeks. Administration of FireMaster BP-6 (150 mg/kg IP) also resulted in an induction of several monooxygenase activities. Arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation were increased by 6-, 3,- and 25-fold, respectively. Only the latter two activities remained elevated two weeks post-injection. Ethylmorphine-N-demethylation was unaffected by the polyhalogenated biphenyls. Significant increases in P-450 hemoprotein were not observed after pretreatment with any of the polyhalogenated biphenyls studied. PMID:209992

  12. Library of biphenyl privileged substructures using a safety-catch linker approach

    DEFF Research Database (Denmark)

    Severinsen, Rune; Bourne, Gregory T; Tran, Tran T

    2008-01-01

    A biphenyl privileged structure library containing three attachment points were synthesized using a catechol-based safety-catch linker strategy. The method requires the attachment of a bromo-acid to the linker, followed by a Pd-catalyzed Suzuki cross-coupling reaction. Further derivatization...

  13. ANALYSIS OF SOIL AND DUST SAMPLES FOR POLYCHLORINATED BIPHENYLS BY ENZYME LINKED IMMUNOSORBENT ASSAY (ELISA)

    Science.gov (United States)

    An inhibition enzyme-linked immunosorbent assay (ELISA) was used to determine polychlorinated biphenyls (PCBs) in house dust and soil. Soil and house dust samples were analyzed for PCB by both gas chromatography/electron capture detection (GC/ECD) and ELISA methods. A correlati...

  14. [Determination of biphenyl ether herbicides in water using HPLC with cloud-point extraction].

    Science.gov (United States)

    He, Cheng-Yan; Li, Yuan-Qian; Wang, Shen-Jiao; Ouyang, Hua-Xue; Zheng, Bo

    2010-01-01

    To determine residues of multiple biphenyl ether herbicides simultaneously in water using high performance liquid chromatography (HPLC) with cloud-point extraction. The residues of eight biphenyl ether herbicides (including bentazone, fomesafen, acifluorfen, aclonifen, bifenox, fluoroglycofenethy, nitrofen, oxyfluorfen) in water samples were extracted with cloud-point extraction of Triton X-114. The analytes were separated and determined using reverse phase HPLC with ultraviolet detector at 300 nm. Optimized conditions for the pretreatment of water samples and the parameters of chromatographic separation applied. There was a good linear correlation between the concentration and the peak area of the analytes in the range of 0.05-2.00 mg/L (r = 0.9991-0.9998). Except bentazone, the spiked recoveries of the biphenyl ether herbicides in the water samples ranged from 80.1% to 100.9%, with relative standard deviations ranging from 2.70% to 6.40%. The detection limit of the method ranged from 0.10 microg/L to 0.50 microg/L. The proposed method is simple, rapid and sensitive, and can meet the requirements of determination of multiple biphenyl ether herbicides simultaneously in natural waters.

  15. Allee effect in polar bears: A potential consequence of polychlorinated biphenyl contamination.

    Czech Academy of Sciences Publication Activity Database

    Pavlová, Viola; Nabe-Nielsen, J.; Dietz, R.; Sonne, C.; Grimm, V.

    2016-01-01

    Roč. 283, č. 1843 (2016), č. článku 20161883. ISSN 0962-8452 Institutional support: RVO:60077344 Keywords : allee effect * polychlorinated biphenyls * polar bears * male reproduction Subject RIV: EH - Ecology, Behaviour Impact factor: 4.940, year: 2016

  16. Uptake of polychlorinated biphenyls and organochlorine pesticides from soil and air into radishes (Raphanus sativus)

    DEFF Research Database (Denmark)

    Mikes, Ondrej; Cupr, P.; Trapp, Stefan

    2009-01-01

    Uptake of organochlorine pesticides and polychlorinated biphenyls from soil and air into radishes was measured at a heavily contaminated field site. The highest contaminant concentrations were found for DDT and its metabolites, and for beta-hexachlorocyclohexane. Bioconcentration factor (BCF, def...

  17. Reductive Dechlorination of Polychlorinated Biphenyls in Marine Sediments

    National Research Council Canada - National Science Library

    Sowers, Kevin

    1999-01-01

    ... Community by Comparative Sequence Analysis of Genes Coding for 16S rRNA, Microbial Reductive Dechlorination of Aroclor 1260 in Anaerobic Slurries of Estuarine Sediments, Differential RFLP patterns of PCR...

  18. Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening

    Directory of Open Access Journals (Sweden)

    Guoqing Zhang

    2018-03-01

    Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1 is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 μM on enzymatic level and 89.11 μM on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 μM on both enzymatic level and cellular level. The structure–activity relationship (SAR of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development.

  19. Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening

    Science.gov (United States)

    Zhang, Guoqing; Xing, Jing; Wang, Yulan; Wang, Lihao; Ye, Yan; Lu, Dong; Zhao, Jihui; Luo, Xiaomin; Zheng, Mingyue; Yan, Shiying

    2018-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 μM on enzymatic level and 89.11 μM on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 μM on both enzymatic level and cellular level. The structure–activity relationship (SAR) of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development. PMID:29651242

  20. Insights into the Reaction Mechanism of Aromatic Ring Cleavage by Homogentisate Dioxygenase: A Quantum Mechanical/Molecular Mechanical Study.

    Science.gov (United States)

    Qi, Yue; Lu, Jiarui; Lai, Wenzhen

    2016-05-26

    To elucidate the reaction mechanism of the ring cleavage of homogentisate by homogentisate dioxygenase, quantum mechanical/molecular mechanical (QM/MM) calculations were carried out by using two systems in different protonation states of the substrate C2 hydroxyl group. When the substrate C2 hydroxyl group is ionized (the ionized pathway), the superoxo attack on the substrate is the rate-limiting step in the catalytic cycle, with a barrier of 15.9 kcal/mol. Glu396 was found to play an important role in stabilizing the bridge species and its O-O cleavage product by donating a proton via a hydrogen-bonded water molecule. When the substrate C2 hydroxyl group is not ionized (the nonionized pathway), the O-O bond cleavage of the bridge species is the rate-limiting step, with a barrier of 15.3 kcal/mol. The QM/MM-optimized geometries for the dioxygen and alkylperoxo complexes using the nonionized model (for the C2 hydroxyl group) are in agreement with the experimental crystal structures, suggesting that the C2 hydroxyl group is more likely to be nonionized.

  1. Docking studies of antidepressants against single crystal structure of tryptophan 2, 3-dioxygenase using Molegro Virtual Docker software.

    Science.gov (United States)

    Dawood, Shazia; Zarina, Shamshad; Bano, Samina

    2014-09-01

    Tryptophan 2, 3-dioxygenase (TDO) a heme containing enzyme found in mammalian liver is responsible for tryptophan (Trp) catabolism. Trp is an essential amino acid that is degraded in to N-formylkynurenine by the action of TDO. The protein ligand interaction plays a significant role in structural based drug designing. The current study illustrates the binding of established antidepressants (ADs) against TDO enzyme using in-silico docking studies. For this purpose, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Seproxetine, Citalopram, Moclobamide, Hyperforin and Amoxepine were selected. In-silico docking studies were carried out using Molegro Virtual Docker (MVD) software. Docking results show that all ADs fit well in the active site of TDO moreover Hyperforin and Paroxetine exhibited high docking scores of -152.484k cal/mol and -139.706k cal/mol, respectively. It is concluded that Hyperforin and Paroxetine are possible lead molecules because of their high docking scores as compared to other ADs examined. Therefore, these two ADs stand as potent inhibitors of TDO enzyme.

  2. Indoleamine 2,3-Dioxygenase Is Dispensable for The Immunomodulatory Function of Stem Cells from Human Exfoliated Deciduous Teeth.

    Science.gov (United States)

    Alipour, Razieh; Masoumi Karimi, Masoumeh; Hashemi-Beni, Batool; Adib, Minoo; Sereshki, Nasrin; Sadeghi, Farzaneh

    2017-01-01

    In this study, we sought to better understand the immunoregulatory function of stem cells derived from human exfoliated deciduous teeth (SHED). We studied the role of the interferon gamma (IFN-γ)-indoleamine 2,3-dioxygenase (IDO)-axis in immunoregulation of SHED compared to bone marrow derived mesenchymal stem cells (BMMSCs) under the same conditions. In this cross-sectional study, recently isolated human T cells were stimulated either by mitogen or inactivated allogeneic peripheral blood mononuclear cells (PBMCs). These T cells were subsequently co-cultured with, either SHED or BMMSCs in the presence or absence of 1-methyl-tryptophan (1-MT) or neutralizing anti- human-IFN-γ antibodies. In all co-cultures we evaluated lymphocyte activation as well as IDO activity. SHED, similar to conventional BMMSCs, had anti-proliferative effects on stimulated T cells and reduced their cytokine production. This property of SHED and BMMSCs was changed by IFN-γ neutralization. We detected IDO in the immunosuppressive supernatant of all co-cultures. Removal of IDO decreased the immunosuppression of BMMSCs. SHED, like BMMSCs, produced the IDO enzyme. Although IFN-γ is one of inducer of IDO production in SHED, these cells were not affected by IFN-γ in the same manner as BMMSCs. Unlike BMMSCs, the IDO enzyme did not contribute to their immunosuppression and might have other cell-type specific roles.

  3. Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.

    Science.gov (United States)

    Valladares, Ricardo; Bojilova, Lora; Potts, Anastasia H; Cameron, Evan; Gardner, Christopher; Lorca, Graciela; Gonzalez, Claudio F

    2013-04-01

    In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development. The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO). Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats. Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA. IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells. L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1.4-fold elevation in 5-HT levels. H₂O₂ produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3.9-fold increase in ileum lumen H₂O₂. L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment. These data support the role of H₂O₂ in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H₂O₂ on host physiology.

  4. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

    Science.gov (United States)

    Heisler, Jillian M.; O’Connor, Jason C.

    2015-01-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

  5. Indole-based assay to assess the effect of ethanol on Pseudomonas putida F1 dioxygenase activity.

    Science.gov (United States)

    da Silva, Márcio Luis Busi; Alvarez, Pedro J J

    2010-06-01

    Toluene dioxygenase (TDO) is ubiquitous in nature and has a broad substrate range, including benzene, toluene, ethylbenzene and xylenes (BTEX). Pseudomonas putida F1 (PpF1) induced on toluene is known to produce indigo from indole through the activity of TDO. In this work, a spectrophotometric assay previously developed to measure indole to indigo production rates was modified to characterize the effects of various ethanol concentrations on toluene aerobic biodegradation activity and assess catabolite repression of TDO. Indigo production rate by cells induced on toluene alone was 0.0012 +/- 0.0006 OD(610) min(-1). The presence of ethanol did not fully repress TDO activity when toluene was also available as a carbon source. However, indigo production rates by PpF1 grown on ethanol:toluene mixtures (3:1 w/w) decreased by approximately 50%. Overall, the proposed spectrophotometric assay is a simple approach to quantify TDO activity, and demonstrates how the presence of ethanol in groundwater contaminated with reformulated gasoline is likely to interfere with naturally occurring microorganisms from fully expressing their aerobic catabolic potential towards hydrocarbons bioremediation.

  6. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

    Science.gov (United States)

    Heisler, Jillian M; O'Connor, Jason C

    2015-11-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

  7. Relationship of Abortion and the Expression of Indoleamine 2,3- dioxygenase (IDO) in Villus and Syncytiotrophoblasts

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the relationship of abortion and the expression of indoleamine 2,3- dioxygenase (IDO) in villus and syncytiotrophoblast in vitro.Methods RT-PCR was applied to analyze the mRNA transcription of IDO in villus of normal pregnancy and inevitable abortion and JAR cells as well. Immunohistochemistry was applied to analyze the expression of IDO protein in villus. Western blot was applied to determinate the expression of IDO protein on cultured syncytiotrophoblast. Highperformance liquid chromatography was applied to determinate whether there was kynurenine in cell culture medium of syncytiotrophoblast.Results The expression of IDO mRNA and protein in villus of inevitable abortion was lower than that of normal pregnancy; IDO mRNA did not express in JAR cells. IDO protein expressed on cultured syncytiotrophoblast, and there was kynurenine in cell culture medium of syncytiotrophoblast.Conclusion Appropriate expression of IDO in villus is necessary for maintenance of normal pregnancy and an active IDO protein expresses in syncytiotrophoblast.

  8. Refining the reaction mechanism of O2 towards its co-substrate in cofactor-free dioxygenases

    Directory of Open Access Journals (Sweden)

    Pedro J. Silva

    2016-12-01

    Full Text Available Cofactor-less oxygenases perform challenging catalytic reactions between singlet co-substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In 1-H-3-hydroxy-4-oxoquinaldine-2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from co-substrate to O2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the co-substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.

  9. New Insight into the Cleavage Reaction of Nostoc sp. Strain PCC 7120 Carotenoid Cleavage Dioxygenase in Natural and Nonnatural Carotenoids

    Science.gov (United States)

    Heo, Jinsol; Kim, Se Hyeuk

    2013-01-01

    Carotenoid cleavage dioxygenases (CCDs) are enzymes that catalyze the oxidative cleavage of carotenoids at a specific double bond to generate apocarotenoids. In this study, we investigated the activity and substrate preferences of NSC3, a CCD of Nostoc sp. strain PCC 7120, in vivo and in vitro using natural and nonnatural carotenoid structures. NSC3 cleaved β-apo-8′-carotenal at 3 positions, C-13C-14, C-15C-15′, and C-13′C-14′, revealing a unique cleavage pattern. NSC3 cleaves the natural structure of carotenoids 4,4′-diaponeurosporene, 4,4′-diaponeurosporen-4′-al, 4,4′-diaponeurosporen-4′-oic acid, 4,4′-diapotorulene, and 4,4′-diapotorulen-4′-al to generate novel cleavage products (apo-14′-diaponeurosporenal, apo-13′-diaponeurosporenal, apo-10′-diaponeurosporenal, apo-14′-diapotorulenal, and apo-10′-diapotorulenal, respectively). The study of carotenoids with natural or nonnatural structures produced by using synthetic modules could provide information valuable for understanding the cleavage reactions or substrate preferences of other CCDs in vivo and in vitro. PMID:23524669

  10. The occurrence and significance of polychlorinated biphenyls in the environment

    Science.gov (United States)

    Dustman, E.H.; Stickel, L.F.; Blus, L.J.; Reichel, W.L.; Wiemeyer, Stanley N.

    1971-01-01

    SUMMARY: Polychlorinated biphenyls constitute a group of chlorine-bearing compounds of industrial origin that have permeated the natural environment throughout the world. Their chemical structure resembles that of some of the organochlorine pesticides. They are troublesome interferences in gas chromatographic analysis of these pesticides. Although methods have been developed to overcome analytical problems, measurements of quantity still are only approximate. Special studies in the United States, Netherlands, and Great Britain have traced PCB's to industrial effluent, but other possible sources have not been followed. Their use in paints, cartons, and insulating fluids suggests that environmental pollution may be from many different sources. PCB's are present in fish and wildlife in many countries of the world. Quantities are higher in animals living near industrial areas. PCB's build up in biological food chains with increases of tens to thousands of times from lower to higher organisms. Experimental studies have shown that PCB's have a toxicity to mallards, pheasants, bobwhite quail, coturnix quail, red-winged blackbirds, starlings, cowbirds, and grackles that is of the same order as the toxicity of DDE to these species. Overt signs of poisoning also are similar to those caused by compounds of the DDT group. Toxic effects of DDE and Aroclor 1254 to coturnix chicks were additive, but not synergistic. PCB's containing higher percentages of chlorine are more toxic to birds than those containing lower percentages. PCB's of foreign manufacture contained contaminants to an extent that greatly increased their toxicity Aroclor 1242. Statistical evaluations of the role that different chemicals may play in thinning of eggshells of brown pelicans show that DDE residues correlate better with shell thinning than do residues of dieldrin or PCB's. Studies of the effects of PCB's in the environment are as yet insufficient for well-rounded conclusions. The evidence available

  11. Production of metabolites from chloro biphenyls by resting cells of Pseudomonas strain LB400 after growth on different carbon sources

    International Nuclear Information System (INIS)

    Billingsley, K.A.; Ward, O.P.

    1999-01-01

    The transformation of polychlorinated biphenyl (PCB), when exposed to microorganisms, into chlorobenzoic acid metabolites was studied. PCBs are widely used in electrical transformers and have become widely dispersed in the environment. A proposed system for clean up of PCBs involves the combined use of anaerobic reductive dehalogenation of highly chlorinated congeners followed by aerobic degradation of moderately chlorinated PCBs, mediated by oxidative ring attack. Much of this work focused on biphenyl-grown cells, in particular Pseudomonas strain LB400 grown on biphenyl, which contains a multicomponent enzyme system. It was shown that resting cells of Pseudomonas strain LB400, grown on glycerol or glucose, could also transform purified PCB congeners and mixtures of PCBs in Aroclors, however, transformation rates were less than those observed with biphenyl-grown cells. 29 refs., 2 tabs., 2 figs

  12. Proof of concept for the use of macroinvertebrates as indicators of polychlorinated biphenyls (PCB) contamination in Lake Hartwell

    Science.gov (United States)

    The U.S. Environmental Protection Agency (EPA) has been conducting research to develop methods and tools for the evaluation of monitored natural recovery (MNR) of sediments contaminated with polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and other lega...

  13. Evaluating Chemical Reactivity And Mechanical Stability Of Nano Palladized Iron Embedded In Activated Carbon On Dechlorination Of Polychlorinated Biphenyls

    Science.gov (United States)

    Remediation of contaminated sites with hydrophobic organic compounds such as polychlorinated biphenyls (PCBs) remains a scientific and technical challenge. The high stability, low aqueous solubility, and high organic affinity of PCBs make them difficult to treat. Many physical,...

  14. Indoleamine 2,3-dioxygenase 1 (IDO1 activity correlates with immune system abnormalities in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Bonanno Giuseppina

    2012-12-01

    Full Text Available Abstract Background Multiple myeloma (MM is a plasma cell malignancy with a multifaceted immune dysfunction. Indoleamine 2,3-dioxygenase 1 (IDO1 degrades tryptophan into kynurenine (KYN, which inhibits effector T cells and promote regulatory T-cell (Treg differentiation. It is presently unknown whether MM cells express IDO1 and whether IDO1 activity correlates with immune system impairment. Methods We investigated IDO1 expression in 25 consecutive patients with symptomatic MM and in 7 patients with either monoclonal gammopathy of unknown significance (MGUS; n=3 or smoldering MM (SMM; n=4. IDO1-driven tryptophan breakdown was correlated with the release of hepatocyte growth factor (HGF and with the frequency of Treg cells and NY-ESO-1-specific CD8+ T cells. Results KYN was increased in 75% of patients with symptomatic MM and correlated with the expansion of CD4+CD25+FoxP3+ Treg cells and the contraction of NY-ESO-1-specific CD8+ T cells. In vitro, primary MM cells promoted the differentiation of allogeneic CD4+ T cells into bona fide CD4+CD25hiFoxP3hi Treg cells and suppressed IFN-γ/IL-2 secretion, while preserving IL-4 and IL-10 production. Both Treg expansion and inhibition of Th1 differentiation by MM cells were reverted, at least in part, by d,l-1-methyl-tryptophan, a chemical inhibitor of IDO. Notably, HGF levels were higher within the BM microenvironment of patients with IDO+ myeloma disease compared with patients having IDO- MM. Mechanistically, the antagonism of MET receptor for HGF with SU11274, a MET inhibitor, prevented HGF-induced AKT phosphorylation in MM cells and translated into reduced IDO protein levels and functional activity. Conclusions These data suggest that IDO1 expression may contribute to immune suppression in patients with MM and possibly other HGF-producing cancers.

  15. Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase.

    Directory of Open Access Journals (Sweden)

    Michael B Cheung

    Full Text Available Respiratory syncytial virus (RSV has been reported to infect human mesenchymal stem cells (MSCs but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts. RSV-infected MSCs showed differentially altered expression of cytokines and chemokines such as IL-1β, IL6, IL-8 and SDF-1 compared to epithelial cells. Notably, RSV-infected MSCs exhibited significantly increased expression of IFN-β (~100-fold and indoleamine-2,3-dioxygenase (IDO (~70-fold than in mock-infected MSCs. IDO was identified in cytosolic protein of infected cells by Western blots and enzymatic activity was detected by tryptophan catabolism assay. Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their proliferation in a dose dependent manner. This effect on PBMC activation was reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated knockout of IDO in MSCs. Neutralizing IFN-β prevented IDO expression and activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a specific inhibitor of the TLR3/dsRNA complex, prevented IFN-β and IDO expression. Together, these results suggest that RSV infection of MSCs alters their immune regulatory function by upregulating IFN-β and IDO, affecting immune cell proliferation, which may account for the lack of protective RSV immunity and for chronicity of RSV-associated lung diseases such as asthma and COPD.

  16. The modulation of enzyme indoleamine 2,3-dioxygenase from dendritic cells for the treatment of type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Abram DM

    2017-07-01

    Full Text Available Débora Moitinho Abram,1 Luis Gustavo Romani Fernandes,1,2 Antônio Celso Saragossa Ramos Filho,2 Patrícia Ucelli Simioni2–4 1Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil; 2Department of Biomedical Science, Faculty of Americana, Americana, SP, Brazil; 3Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP, Campinas, SP, Brazil; 4Department of Biochemistry and Microbiology, Institute of Biosciences, Universidade Estadual Paulista, UNESP, Rio Claro, SP, Brazil Abstract: Diabetes mellitus type 1 (DM1 is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs. It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism. Current studies on immunotherapies describe the use of DC and IDO to control the progression of the immune response that triggers DM1. The initial results obtained are promising and indicate the possibility of developing therapies for the treatment or prevention of the DM1. Clinical trials using these cells in DM1 patients represent an interesting alternative treatment. However, clinical trials are still in the initial phase and a robust group of assays is necessary. Keywords: autoimmunity, immunoregulation, diabetes mellitus type 1, clinical trials, dendritic cells, indoleamine, tryptophan

  17. Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

    Directory of Open Access Journals (Sweden)

    Jacques C Mbongue

    Full Text Available Dendritic cells (DC interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS. Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1. Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention

  18. Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest

    Science.gov (United States)

    Tarade, Daniel; Ma, Dennis; Pignanelli, Christopher; Mansour, Fadi; Simard, Daniel; van den Berg, Sean; Gauld, James; McNulty, James; Pandey, Siyaram

    2017-01-01

    The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents. PMID:28253265

  19. Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest.

    Directory of Open Access Journals (Sweden)

    Daniel Tarade

    Full Text Available The cis-stilbene, combretastatin A4 (CA4, is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents.

  20. Replacement of Tyrosine 181 by Phenylalanine in Gentisate 1,2-Dioxygenase I from Pseudomonas alcaligenes NCIMB 9867 Enhances Catalytic Activities

    Science.gov (United States)

    Tan, Chew Ling; Yeo, Chew Chieng; Khoo, Hoon Eng; Poh, Chit Laa

    2005-01-01

    xlnE, encoding gentisate 1,2-dioxygenase (EC 1.13.11.4), from Pseudomonas alcaligenes (P25X) was mutagenized by site-directed mutagenesis. The mutant enzyme, Y181F, demonstrated 4-, 3-, 6-, and 16-fold increases in relative activity towards gentisate and 3-fluoro-, 4-methyl-, and 3-methylgentisate, respectively. The specific mutation conferred a 13-fold higher catalytic efficiency (kcat/Km) on Y181F towards 3-methylgentisate than that of the wild-type enzyme. PMID:16237038

  1. Determination of vaporization enthalpies of polychlorinated biphenyls by correlation gas chromatography.

    Science.gov (United States)

    Puri, S; Chickos, J S; Welsh, W J

    2001-04-01

    The vaporization enthalpies of 16 polychlorinated biphenyls have been determined by correlation gas chromatography. This study was prompted by the realization that the vaporization enthalpy of the standard compounds used in previous studies, octadecane and eicosane, were values measured at 340 and 362 K, respectively, rather than at 298 K. Adjustment to 298 K amounts to a 7-8 kJ/mol increment in the values. With the inclusion of this adjustment, vaporization enthalpies evaluated by correlation gas chromatography are in good agreement with the values determined previously in the literature. The present results are based on the vaporization enthalpies of several standards whose values are well established in the literature. The standards include a variety of n-alkanes and various chlorinated hydrocarbons. The vaporization enthalpies of PCBs increased with the number of chlorine atoms and were found to be larger for meta- and para-substituted polychlorinated biphenyls.

  2. Polychlorinated Biphenyl-Xenobiotic Nuclear Receptor Interactions Regulate Energy Metabolism, Behavior, and Inflammation in Non-alcoholic-Steatohepatitis.

    Science.gov (United States)

    Wahlang, Banrida; Prough, Russell A; Falkner, K Cameron; Hardesty, Josiah E; Song, Ming; Clair, Heather B; Clark, Barbara J; States, J Christopher; Arteel, Gavin E; Cave, Matthew C

    2016-02-01

    Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis and activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate PCB interactions with the pregnane-xenobiotic receptor (Pxr: Nr1i2) and constitutive androstane receptor (Car: Nr1i3) in NASH. Wild type C57Bl/6 (WT), Pxr(-/-) and Car(-/-) mice were fed the high fat diet (42% milk fat) and exposed to a single dose of Aroclor 1260 (20 mg/kg) in this 12-week study. Metabolic phenotyping and analysis of serum, liver, and adipose was performed. Steatohepatitis was pathologically similar in all Aroclor-exposed groups, while Pxr(-/-) mice displayed higher basal pro-inflammatory cytokine levels. Pxr repressed Car expression as evident by increased basal Car/Cyp2b10 expression in Pxr(-/-) mice. Both Pxr(-/-) and Car(-/-) mice showed decreased basal respiratory exchange rate (RER) consistent with preferential lipid metabolism. Aroclor increased RER and carbohydrate metabolism, associated with increased light cycle activity in both knockouts, and decreased food consumption in the Car(-/-) mice. Aroclor exposure improved insulin sensitivity in WT mice but not glucose tolerance. The Aroclor-exposed, Pxr(-/-) mice displayed increased gluconeogenic gene expression. Lipid-oxidative gene expression was higher in WT and Pxr(-/-) mice although RER was not changed, suggesting PCB-mediated mitochondrial dysfunction. Therefore, Pxr and Car regulated inflammation, behavior, and energy metabolism in PCB-mediated NASH. Future studies should address the 'off-target' effects of PCBs in steatohepatitis. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

  3. Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc finger modules.

    Directory of Open Access Journals (Sweden)

    Nan Liu

    Full Text Available Tet proteins are emerging as major epigenetic modulators of cell fate and plasticity. However, little is known about how Tet proteins are targeted to selected genomic loci in distinct biological contexts. Previously, a CXXC-type zinc finger domain in Tet1 was shown to bind CpG-rich DNA sequences. Interestingly, in human and mouse the Tet2 and Tet3 genes are adjacent to Cxxc4 and Cxxc10-1, respectively. The CXXC domains encoded by these loci, together with those in Tet1 and Cxxc5, identify a distinct homology group within the CXXC domain family. Here we provide evidence for alternative mouse Tet3 transcripts including the Cxxc10-1 sequence (Tet3(CXXC and for an interaction between Tet3 and Cxxc4. In vitro Cxxc4 and the isolated CXXC domains of Tet1 and Tet3(CXXC bind DNA substrates with similar preference towards the modification state of cytosine at a single CpG site. In vivo Tet1 and Tet3 isoforms with and without CXXC domain hydroxylate genomic 5-methylcytosine with similar activity. Relative transcript levels suggest that distinct ratios of Tet3(CXXC isoforms and Tet3-Cxxc4 complex may be present in adult tissues. Our data suggest that variable association with CXXC modules may contribute to context specific functions of Tet proteins.

  4. CLOSURE REPORT FOR CORRECTIVE ACTION UNIT 528: POLYCHLORINATED BIPHENYLS CONTAMINATION NEVADA TEST SITE, NEVADA

    Energy Technology Data Exchange (ETDEWEB)

    BECHTEL NEVADA

    2006-09-01

    This Closure Report (CR) describes the closure activities performed at CAU 528, Polychlorinated Biphenyls Contamination, as presented in the Nevada Division of Environmental Protection (NDEP)-approved Corrective Action Plan (CAP) (US. Department of Energy, National Nuclear Security Administration Nevada Site Office [NNSAINSO], 2005). The approved closure alternative was closure in place with administrative controls. This CR provides a summary of the completed closure activities, documentation of waste disposal, and analytical data to confirm that the remediation goals were met.

  5. Photoionization and Electron Transfer of Biphenyl within the Channels of Al-ZSM-5 Zeolites.

    Science.gov (United States)

    Gener, Isabelle; Buntinx, Guy; Brémard, Claude

    1999-06-14

    Evidence of the photogenerated long-lived biphenyl radical and a trapped electron in the void space of aluminated nonacidic ZSM-5 zeolites has been obtained from the time-resolved UV/Vis absorption, Raman scattering, and EPR spectra. The restoration of the ground states implicates the existence of long-lived positive holes in the framework. © 1999 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.

  6. Polychlorinated biphenyls and reproductive hormones in female polar bears at Svalbard.

    OpenAIRE

    Haave, Marte; Ropstad, Erik; Derocher, Andrew E; Lie, Elisabeth; Dahl, Ellen; Wiig, Øystein; Skaare, Janneche U; Jenssen, Bjørn Munro

    2003-01-01

    High concentrations of polychlorinated biphenyls (PCBs) in polar bears from Svalbard have increased concern for that population's reproductive health. We examined whether there were associations between the plasma concentrations of PCBs and reproductive hormones [progesterone (P4)] and 17 beta-estradiol (E2)] in free-living female polar bears from Svalbard. Concentrations of P4 depended on reproductive status, and concentrations were lowest in females with offspring--females with cubs and fem...

  7. Importance of Passive Diffusion in the Uptake of Polychlorinated Biphenyls by Phagotrophic Protozoa†

    OpenAIRE

    Kujawinski, Elizabeth B.; Farrington, John W.; Moffett, James W.

    2000-01-01

    Unicellular protozoan grazers represent a size class of organisms where a transition in the mechanism of chlorobiphenyl (CB) introduction, from diffusion through surface membranes to ingestion of contaminated prey, could occur. This study compares the relative importance of these two processes in the overall uptake of polychlorinated biphenyls by protists. Uptake rates and steady-state concentrations were compared in laboratory cultures of grazing and nongrazing protozoa. These experiments we...

  8. A new biphenyl derivative from the mangrove endophytic fungus Phomopsis longicolla HL-2232.

    Science.gov (United States)

    Li, Xiao-Bao; Chen, Guang-Ying; Liu, Rui-Jie; Zheng, Cai-Juan; Song, Xin-Ming; Han, Chang-Ri

    2017-10-01

    A new biphenyl derivative 5,5'-dimethoxybiphenyl-2,2'-diol (1), together with five known compounds (2-5), was isolated from the mangrove endophytic fungus Phomopsis longicolla HL-2232. The structures of these compounds were elucidated using comprehensive spectroscopic methods. The absolute configuration of 4 was determined by single-crystal X-ray diffraction for the first time. The inhibitory activities of all compounds against two Vibrio bacteria were evaluated.

  9. TET1-Mediated Hydroxymethylation Facilitates Hypoxic Gene Induction in Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Christopher J. Mariani

    2014-06-01

    Full Text Available The ten-eleven-translocation 5-methylcytosine dioxygenase (TET family of enzymes catalyzes the conversion of 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, a modified cytosine base that facilitates gene expression. Cells respond to hypoxia by inducing a transcriptional program regulated in part by oxygen-dependent dioxygenases that require Fe(II and α-ketoglutarate. Given that the TET enzymes also require these cofactors, we hypothesized that the TETs regulate the hypoxia-induced transcriptional program. Here, we demonstrate that hypoxia increases global 5-hmC levels, with accumulation of 5-hmC density at canonical hypoxia response genes. A subset of 5-hmC gains colocalize with hypoxia response elements facilitating DNA demethylation and HIF binding. Hypoxia results in transcriptional activation of TET1, and full induction of hypoxia-responsive genes and global 5-hmC increases require TET1. Finally, we show that 5-hmC increases and TET1 upregulation in hypoxia are HIF-1 dependent. These findings establish TET1-mediated 5-hmC changes as an important epigenetic component of the hypoxic response.

  10. Transcriptomics identifies differences between ultrapure non-dioxin-like polychlorinated biphenyls (PCBs) and dioxin-like PCB126 in cultured peripheral blood mononuclear cells

    International Nuclear Information System (INIS)

    Wens, B.; De Boever, P.; Maes, M.; Hollanders, K.; Schoeters, G.

    2011-01-01

    Polychlorinated biphenyls (PCBs) remain ubiquitously present in human lipids despite the ban on their production and use. Their presence can be chemically monitored in peripheral blood samples of the general population. We tested whether in vitro exposure to different PCB congeners induced different gene expression profiles in peripheral blood cells. We have isolated peripheral blood mononuclear cells (PBMC) from whole blood of 8 healthy individuals and exposed these cells in vitro to individual non-dioxin-like (NDL)-PCB congeners (PCB52, 138 or 180; 10 μM) or dioxin-like (DL)-PCB congener PCB126 (1 μM) during 18 h. Differential gene expression response was measured using Agilent whole-human genome microarrays. Two-way ANOVA analysis of the data showed that both gender and PCB exposure are important factors influencing gene expression responses in blood cells. Hierarchical cluster analysis of genes influenced by PCB exposure, revealed that DL-PCB126 induced a different gene expression response compared to the NDL-PCBs. Biological interpretation of the results revealed that exposure to PCB126 induced the AhR signaling pathway, whereas the induction of nuclear receptor pathways by the NDL-PCBs was limited in blood cells. Nevertheless, molecular responses of blood cells to individual PCB congeners revealed significantly expressed genes that play a role in biological functions and processes known to be affected by PCB exposure in vivo. Observed gene expression changes in this in vitro model were found to be related to hepatotoxicity, immune and inflammatory response and disturbance of lipid and cholesterol homeostasis.

  11. Preparation, crystallization and X-ray diffraction analysis to 1.5 Å resolution of rat cysteine dioxygenase, a mononuclear iron enzyme responsible for cysteine thiol oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, Chad R. [Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853-8001 (United States); Hao, Quan [MacCHESS at the Cornell High Energy Synchrotron Source, Cornell University, Ithaca, NY 14853-8001 (United States); Stipanuk, Martha H., E-mail: mhs6@cornell.edu [Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853-8001 (United States)

    2005-11-01

    Recombinant rat cysteine dioxygenase (CDO) has been expressed, purified and crystallized and X-ray diffraction data have been collected to 1.5 Å resolution. Cysteine dioxygenase (CDO; EC 1.13.11.20) is an ∼23 kDa non-heme iron metalloenzyme that is responsible for the oxidation of cysteine by O{sub 2}, yielding cysteinesulfinate. CDO catalyzes the first step in the conversion of cysteine to taurine, as well as the first step in the catabolism of cysteine to pyruvate plus sulfate. Recombinant rat CDO was heterologously expressed, purified and crystallized. The protein was expressed as a fusion protein bearing a polyhistidine tag to facilitate purification, a thioredoxin tag to improve solubility and a factor Xa cleavage site to permit removal of the entire N-terminus, leaving only the 200 amino acids inherent to the native protein. A multi-step purification scheme was used to achieve >95% purity of CDO. The optimal CDO crystals diffracted to 1.5 Å resolution and belonged to space group P4{sub 3}2{sub 1}2 or P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 57.55, c = 123.06 Å, α = β = γ = 90°. CDO shows little homology to any other proteins; therefore, the structure of the enzyme will be determined by ab initio phasing using a selenomethionyl derivative.

  12. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

    Science.gov (United States)

    Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

    2016-04-05

    Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Expression, purification, crystallization and preliminary X-ray analysis of a novel N-substituted branched-chain l-amino-acid dioxygenase from Burkholderia ambifaria AMMD

    International Nuclear Information System (INIS)

    Qin, Hui-Min; Miyakawa, Takuya; Nakamura, Akira; Xue, You-Lin; Kawashima, Takashi; Kasahara, Takuya; Hibi, Makoto; Ogawa, Jun; Tanokura, Masaru

    2012-01-01

    Diffraction data were collected to a limiting resolution of 2.4 Å from a crystal of selenomethionyl-labelled SadA, an l-amino-acid dioxygenase. Ferrous ion- and α-ketoglutarate-dependent dioxygenase from Burkholderia ambifaria AMMD (SadA) catalyzes the C3-hydroxylation of N-substituted branched-chain l-amino acids, especially N-succinyl-l-leucine, coupled to the conversion of α-ketoglutarate to succinate and CO 2 . SadA was expressed in Escherichia coli, purified and crystallized using the sitting-drop vapour-diffusion method at 293 K. Crystals of selenomethionine-substituted SadA were obtained using a reservoir solution containing PEG 3000 as the precipitant at pH 9.5 and diffracted X-rays to 2.4 Å resolution. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 49.3, b = 70.9, c = 148.2 Å. The calculated Matthews coefficient (V M = 2.1 Å 3 Da −1 , 41% solvent content) suggested that the crystal contains two molecules per asymmetric unit

  14. TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation.

    Science.gov (United States)

    Müller, Udo; Bauer, Christina; Siegl, Michael; Rottach, Andrea; Leonhardt, Heinrich

    2014-07-01

    The discovery of hydroxymethyl-, formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase.

    Science.gov (United States)

    Sharma, Rajni; Di Dalmazi, Giulia; Caturegli, Patrizio

    2016-08-01

    Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2(h4) mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. NOD-H2(h4) mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. This study

  16. Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

    Science.gov (United States)

    Sharma, Rajni; Di Dalmazi, Giulia

    2016-01-01

    Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory

  17. Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice

    International Nuclear Information System (INIS)

    Han, Sung Gu; Eum, Sung Yong; Toborek, Michal; Smart, Eric; Hennig, Bernhard

    2010-01-01

    Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.

  18. Polychlorinated biphenyl (PCB) load, lipid reserves and biotransformation activity in migrating Atlantic salmon from River Moerrum, Sweden

    International Nuclear Information System (INIS)

    Hansson, Maria C.; Persson, Maria E.; Larsson, Per; Schantz, Torbjoern von

    2009-01-01

    Atlantic salmon accumulate high levels of contaminants such as polychlorinated biphenyls (PCBs) in their lipids during the adult growth phase spent at sea. The lipids are later utilized during migration for swimming and biological adaptations. We hypothesize that migrating salmons' biotransformation processes are affected by the high levels of built-up PCBs compared to salmon that in a pre-migrational stage. For these analyses we sampled adult Atlantic salmon during migration in the Swedish River Moerrum and measured the 21 most common PCB congeners (ΣPCB) and lipid levels in muscle tissue, aryl hydrocarbon receptor (AHR2) and cytochrome P4501A1 (CYP1A1) transcript levels as well as ethoxyresorufin-O-deethylase activity (EROD) in liver. We also determined which AHR2 genotypes the salmon carried. We show that EROD activity is correlated to CYP1A1 level but not to ΣPCB concentration. ΣPCB concentration does not predict levels of neither the AHR2 nor CYP1A1 genes. We find no associations between specific AHR2 transcription levels and AHR2 genotypes or a correlation between AHR2 and CYP1A1 transcription levels, which is in direct contrast to pre-migrational adult salmon from the Baltic Sea. When we compare River Moerrum to salmon we have previously sampled in the Baltic Sea we show that migrating salmon have significantly lower lipid levels in their muscles; higher muscle concentrations of ΣPCB on a lipid basis; and significantly lower CYP1A1 and EROD levels compared to salmon from the Baltic Sea. Also, transcript levels of three out of four AHR2 genes are significantly different. In conclusion, migrating Swedish Atlantic salmon carry higher concentrations of PCBs in their lipids compared to salmon in the Baltic Sea, but have lower activation of biotransformation genes and enzymes. Our results indicate that accumulated pollutants from the Baltic Sea are deactivated inside the migrating salmon's lipid tissues and increase in concentration when migration is initiated

  19. Transient spectral hole burning observed on the single-molecule level in terrylene-doped biphenyl

    International Nuclear Information System (INIS)

    Pärs, M.; Palm, V.; Kikas, J.

    2014-01-01

    We use the method of fluorescence correlation spectroscopy to analyze the single-molecule (SM) spectroscopy data earlier recorded for a special type of terrylene SM impurity center (referred as “spectrally confined unstable molecule”, SCM) in an incommensurate single crystal of biphenyl. The SCM's SM line seems to be chaotically jumping around within a broad “spectral envelope” and was first considered being subject to a peculiar spectral diffusion behavior. However, our correlation analysis reveals that all the features observed for SCM at 1.8 K are consistent with an assumption that this SM center participates in a process of reversible (transient) spectral hole burning (THB) earlier observed for terrylene-doped polycrystalline biphenyl. No observations of THB processes on SM level have been so far reported for this impurity system, partially due to a low concentration of relevant impurity centers. Another reason making searching for such centers experimentally challenging is an unusual SM line behavior: the photoinduced transition to a metastable “dark state” leads to the SM line saturational broadening, which is much stronger than the triplet broadening. Hence required prolonged observation is often prevented by an SM act of persistent spectral hole burning. - Highlights: • SCM—special type of terrylene single-molecule center in incommensurate biphenyl. • An unusually stable SCM was investigated during several hours at T=1.8 K. • SCM undergoes photoinduced transitions to an unknown metastable “dark state” (DS). • The long DS lifetime causes strong saturational broadening of SCM spectral line. • SCM participates in an earlier observed process of transient hole burning

  20. Detection of Surface-Linked Polychlorinated Biphenyls using Surface-Enhanced Raman Scattering Spectroscopy

    DEFF Research Database (Denmark)

    Rindzevicius, Tomas; Barten, Jan; Vorobiev, Mikhail

    2017-01-01

    We present an improved procedure for analytical detection of toxic polychlorinated biphenyls (PCB) using surface-enhanced Raman scattering (SERS) spectroscopy. A gold-capped silicon nanopillar substrate was utilized to concentrate PCB molecules within an area of high electromagnetic fields through...... formation of microsized nanopillar clusters, and consequently, so-called “hot spots” can be formed. In order to improve PCB detection limit, 3,3',4,4'-tetrachlorobiphenyl (PCB77) compounds were chemically modified with a – SCH3 (PCB77-SCH3) group. Experimental and numerical analysis of vibrational modes...

  1. Secondary sex ratio in relation to exposures to polychlorinated biphenyls, dichlorodiphenyl dichloroethylene and methylmercury

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Choi, Anna L; Petersen, Maria Skaalum

    2017-01-01

    This study was undertaken to assess the potential impact of maternal exposures to polychlorinated biphenyl (PCB), dichlorodiphenyl dichloroethylene (DDE) and methylmercury on the secondary sex ratios (the ratio of male to female live births) over a span of 23 years. The study includes prospective......% CI = 2-17%), respectively, of giving birth to a boy. In conclusion, maternal exposure to ΣPCB, DDE and methylmercury was associated with a slightly increased secondary sex ratio. The impact of paternal exposures could not be taken into account and deserves attention....

  2. Degradation of polychlorinated biphenyls in the rhizosphere of rape, Brassica napus L.

    Science.gov (United States)

    Javorská, Hana; Tlustos, Pavel; Kaliszová, Regina

    2009-06-01

    The objective of this study was to investigate the rhizosphere effect of rape plants on polychlorinated biphenyls (PCB) dissipation in soils spiked with seven indicator congeners. Depletion of PCB in the rhizosphere was significantly higher in the soil with lower organic matter content. While in the Chernozem soil, 87% of PCB related to bulk soil were found in the 1st mm from roots, only 62%-69% were found in the Fluvisol soil with no significant influence of increased initial PCB concentration. Further from the roots, the concentration of lower chlorinated congeners decreased, which indicates their greater biodegradation in comparison with more chlorinated ones.

  3. Polychlorinated biphenyls (PCBs) in the frame of the dismantling of nuclear facilities

    International Nuclear Information System (INIS)

    Hagenbart, Lars; Held, Christian; Reichert, Alexander

    2013-01-01

    During construction and maintenance of nuclear facilities PCB (polychlorinated biphenyls) containing paints were used in a large extent in the past. The WAK dismantling and disposal Company has dismantles such facilities and identified the PCB in the buildings. Besides the radionuclides the conventional hazardous material group of the PCBs has also to be disposed. The respective legal regulations have to be considered. In the frame of the contribution the radiological release of building structures with respect to re-use or demolition and residual PCB containing materials is discussed. The radiological disposal in final repositories and the conventional disposal regulations for releasable residual wastes are reported.

  4. Electrodialytic remediation of polychlorinated biphenyls contaminated soil with iron nanoparticles and two different surfactants

    DEFF Research Database (Denmark)

    Gomes, Helena I.; Dias-Ferreira, Celia; Ottosen, Lisbeth M.

    2014-01-01

    Polychlorinated biphenyls (PCB) are persistent organic pollutants (POP) that strongly adsorb in soils and sediments. There is a need to develop new and cost-effective solutions for the remediation of PCB contaminated soils. The suspended electrodialytic remediation combined with zero valent iron......ZVI showed encouraging tendencies and a base is thus formed for further optimization towards a new method for remediation of PCB polluted soils....... nanoparticles (nZVI) could be a competitive alternative to the commonly adapted solutions of incineration or landfilling. Surfactants can enhance the PCB desorption, dechlorination, and the contaminated soil cleanup. In this work, two different surfactants (saponin and Tween 80) were tested to enhance PCB...

  5. Levels of polychlorinated biphenyls and pesticides in bluefish before and after cooking.

    Science.gov (United States)

    Trotter, W J; Corneliussen, P E; Laski, R R; Vannelli, J J

    1989-01-01

    Similar levels of polychlorinated biphenyls (PCBs), pesticides, and fat were found in 20 correlated uncooked and cooked (baked) bluefish fillets. Fillets averaged 2.5 ppm PCBs as Aroclor 1254 (whole basis) before cooking; after cooking, with the oil drippings and skin discarded, the average PCB level was 2.7 ppm. Although PCBs, lipophilic pesticides, and fat were lost along with oil drippings and skin that were discarded after cooking, the moisture loss in the fillets during cooking compensated for these weight losses almost completely. After the fillets were cooked and the oil drippings and skin were discarded, the PCB content of the fillets was 27% lower on the average.

  6. Analysis the mixtures of polyphenyls by gas chromatrogaphie. 1.- Area response for biphenyl and terphenyls relative to triphenylmethane

    International Nuclear Information System (INIS)

    Perez Garcia, M.

    1966-01-01

    The relative performances of the thermal conductivity and flame ionization detectors towards triphenylmethane were investigated for each one of the components of biphenyl of biphenyl and terphenyl mixtures. The influence of the concentration of the considered compound as well as the influence derived from the present of all other components on the above-mentioned relative performance were studied. A 2 m long column filled with 50-70 mesh stomacher containing 20% apiezon L was used to carry out the study with the thermal conductivity detector by keeping the column at 300 degree centigree using helium gas as carrier. (Author) 13 refs

  7. Biomonitoring of non-dioxin-like polychlorinated biphenyls in transgenic Arabidopsis using the mammalian pregnane X receptor system: a role of pectin in pollutant uptake.

    Directory of Open Access Journals (Sweden)

    Lieming Bao

    Full Text Available Polychlorinated biphenyls (PCBs are persistent organic pollutants damaging to human health and the environment. Techniques to indicate PCB contamination in planta are of great interest to phytoremediation. Monitoring of dioxin-like PCBs in transgenic plants carrying the mammalian aryl hydrocarbon receptor (AHR has been reported previously. Herein, we report the biomonitoring of non-dioxin-like PCBs (NDL-PCBs using the mammalian pregnane X receptor (PXR. In the transgenic Arabidopsis designated NDL-PCB Reporter, the EGFP-GUS reporter gene was driven by a promoter containing 18 repeats of the xenobiotic response elements, while PXR and its binding partner retinoid X receptor (RXR were coexpressed. Results showed that, in live cells, the expression of reporter gene was insensitive to endogenous lignans, carotenoids and flavonoids, but responded to all tested NDL-PCBs in a dose- and time- dependent manner. Two types of putative PCB metabolites, hydroxy- PCBs and methoxy- PCBs, displayed different activation properties. The vascular tissues seemed unable to transport NDL-PCBs, whereas mutation in QUASIMODO1 encoding a 1,4-galacturonosyltransferase led to reduced PCB accumulation in Arabidopsis, revealing a role for pectin in the control of PCB translocation. Taken together, the reporter system may serve as a useful tool to biomonitor the uptake and metabolism of NDL-PCBs in plants.

  8. Enhanced iodide sequestration by 3-biphenyl-5,6-dihydroimidazo 2,1-b thiazole in sodium/iodide sym-porter (NIS)-expressing cells

    International Nuclear Information System (INIS)

    Lecat-Guillet, N.; Ambroise, Y.

    2008-01-01

    The ability of the sodium/iodide sym-porter (NIS) to take up iodide has long provided the basis for cyto-reductive gene therapy and cancer treatment with radio-iodide. One of the major limitations of this approach is that radio-iodide retention in NIS-expressing cells is not sufficient for their destruction. We identified and characterized a small organic molecule capable of increasing iodide retention in HEK293 cells permanently transfected with human NIS cDNA (hNIS-HEK293) and in the rat thyroid-derived cell line FRTL-5. In the presence of 3-biphenyl-4'-yl-5,6-dihydroimidazo[2,1-b)thiazole (ISA1), the transmembrane iodide concentration gradient was increased up to 4.5-fold. Our experiments indicate that the imidazo-thiazole derivative acts either by inhibiting anion efflux mechanisms, or by promoting the relocation of iodide into subcellular compartments. This new compound is not only an attractive chemical tool to investigate the mechanisms of iodide flux at the cellular level, but also opens promising perspectives in the treatment of cancer after NIS gene transfer. (authors)

  9. Phenylpropanoid 2,3-dioxygenase involved in the cleavage of the ferulic acid side chain to form vanillin and glyoxylic acid in Vanilla planifolia.

    Science.gov (United States)

    Negishi, Osamu; Negishi, Yukiko

    2017-09-01

    Enzyme catalyzing the cleavage of the phenylpropanoid side chain was partially purified by ion exchange and gel filtration column chromatography after (NH 4 ) 2 SO 4 precipitation. Enzyme activities were dependent on the concentration of dithiothreitol (DTT) or glutathione (GSH) and activated by addition of 0.5 mM Fe 2+ . Enzyme activity for ferulic acid was as high as for 4-coumaric acid in the presence of GSH, suggesting that GSH acts as an endogenous reductant in vanillin biosynthesis. Analyses of the enzymatic reaction products with quantitative NMR (qNMR) indicated that an amount of glyoxylic acid (GA) proportional to vanillin was released from ferulic acid by the enzymatic reaction. These results suggest that phenylpropanoid 2,3-dioxygenase is involved in the cleavage of the ferulic acid side chain to form vanillin and GA in Vanilla planifolia.

  10. Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO.

    Directory of Open Access Journals (Sweden)

    Juliana Croitoru-Lamoury

    Full Text Available The kynurenine pathway (KP of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO and IDO2, that it is highly regulated by type I (IFN-β and II interferons (IFN-γ, and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.

  11. Remarkable Role of Indoleamine 2,3-Dioxygenase and Tryptophan Metabolites in Infectious Diseases: Potential Role in Macrophage-Mediated Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yuki Murakami

    2013-01-01

    Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1, the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and the subsequent biochemical reactions is essential for the design of therapeutic strategies in certain immune diseases. In this paper, current knowledge about the role of IDO1 and its metabolites during various infectious diseases is presented. Particularly, the regulation of type I interferons (IFNs production via IDO1 in virus infection is discussed. This paper offers insights into new therapeutic strategies in the modulation of viral infection and several immune-related disorders.

  12. Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab

    DEFF Research Database (Denmark)

    Bjørn, Jon; Iversen, Trine Zeeberg; Nitschke, Nikolaj Juul

    2016-01-01

    antibody ipilimumab (ipi). METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response......BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking....... RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded...

  13. Bacterial properties changing under Triton X-100 presence in the diesel oil biodegradation systems: from surface and cellular changes to mono- and dioxygenases activities.

    Science.gov (United States)

    Sałek, Karina; Kaczorek, Ewa; Guzik, Urszula; Zgoła-Grześkowiak, Agnieszka

    2015-03-01

    Triton X-100, as one of the most popular surfactants used in bioremediation techniques, has been reported as an effective agent enhancing the biodegradation of hydrocarbons. However efficient, the surfactant's role in different processes that together enable the satisfying biodegradation should be thoroughly analysed and verified. In this research, we present the interactions of Triton X-100 with the bacterial surfaces (hydrophobicity and zeta potential), its influence on the enzymatic properties (considering mono- and dioxygenases) and profiles of fatty acids, which then all together were compared with the biodegradation rates. The addition of various concentrations of Triton X-100 to diesel oil system revealed different cell surface hydrophobicity (CSH) of the tested strains. The results demonstrated that for Pseudomonas stutzeri strain 9, higher diesel oil biodegradation was correlated with hydrophilic properties of the tested strain and lower Triton X-100 biodegradation. Furthermore, an increase of the branched fatty acids was observed for this strain.

  14. Correlation of circadian changes in tyrosine aminotransferase and tryptophan-2-3-dioxygenase in rat liver to irradiation at different times of the day

    International Nuclear Information System (INIS)

    Toropila, M.; Ahlers, I.; Datelinka, I.; Ahlersova, E.

    1987-01-01

    Male SPF Wistar rats adapted to a 12:12 h light:dark regimen were irradiated at 3-hour intervals in the course of 24 h with a dose of 14.35 Gy of X-rays; 24 h after irradiation or sham irradiation and starvation for the same length of time, and also in fed intact rats, tyrosine aminotransferase and tryptophan-2-3-dioxygenase activities in the liver, and the serum corticosterone level were determined. Although lethal irradiation modified the given enzyme activities, it did not abolish their circadian rhythm, evidently in association with the low sensitivity of the liver to ionizing radiation. In the irradiated animals (compared with sham-irradiated animals), the serum corticosterone concentration fell during the light part of the day and at the beginning of the dark part. (author). 3 figs., 13 refs

  15. Origin of the Proton-transfer Step in the Cofactor-free (1H)-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase

    Science.gov (United States)

    Hernandez-Ortega, Aitor; Quesne, Matthew G.; Bui, Soi; Heuts, Dominic P. H. M.; Steiner, Roberto A.; Heyes, Derren J.; de Visser, Sam P.; Scrutton, Nigel S.

    2014-01-01

    Dioxygenases catalyze a diverse range of chemical reactions that involve the incorporation of oxygen into a substrate and typically use a transition metal or organic cofactor for reaction. Bacterial (1H)-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) belongs to a class of oxygenases able to catalyze this energetically unfavorable reaction without any cofactor. In the quinaldine metabolic pathway, HOD breaks down its natural N-heteroaromatic substrate using a mechanism that is still incompletely understood. Experimental and computational approaches were combined to study the initial step of the catalytic cycle. We have investigated the role of the active site His-251/Asp-126 dyad, proposed to be involved in substrate hydroxyl group deprotonation, a critical requirement for subsequent oxygen reaction. The pH profiles obtained under steady-state conditions for the H251A and D126A variants show a strong pH effect on their kcat and kcat/Km constants, with a decrease in kcat/Km of 5500- and 9-fold at pH 10.5, respectively. Substrate deprotonation studies under transient-state conditions show that this step is not rate-limiting and yield a pKa value of ∼7.2 for WT HOD. A large solvent isotope effect was found, and the pKa value was shifted to ∼8.3 in D2O. Crystallographic and computational studies reveal that the mutations have a minor effect on substrate positioning. Computational work shows that both His-251 and Asp-126 are essential for the proton transfer driving force of the initial reaction. This multidisciplinary study offers unambiguous support to the view that substrate deprotonation, driven by the His/Asp dyad, is an essential requirement for its activation. PMID:24482238

  16. In vitro modulation of cytochrome P450 reductase supported indoleamine 2,3-dioxygenase activity by allosteric effectors cytochrome b(5) and methylene blue.

    Science.gov (United States)

    Pearson, Josh T; Siu, Sophia; Meininger, David P; Wienkers, Larry C; Rock, Dan A

    2010-03-30

    Indoleamine 2,3-dioxygenase (IDO) is a heme-containing dioxygenase involved in the degradation of several indoleamine derivatives and has been indicated as an immunosuppressive. IDO is an attractive target for therapeutic intervention in diseases which are known to capitalize on immune suppression, including cancer, HIV, and inflammatory diseases. Conventionally, IDO activity is measured through chemical reduction by the addition of ascorbate and methylene blue. Identification of potential coenzymes involved in the reduction of IDO in vivo should improve in vitro reconstitution systems used to identify potential IDO inhibitors. In this study we show that NADPH-cytochrome P450 reductase (CPR) is capable of supporting IDO activity in vitro and that oxidation of l-Trp follows substrate inhibition kinetics (k(cat) = 0.89 +/- 0.04 s(-1), K(m) = 0.72 +/- 0.15 microM, and K(i) = 9.4 +/- 2.0 microM). Addition of cytochrome b(5) to CPR-supported l-Trp incubations results in modulation from substrate inhibition to sigmoidal kinetics (k(cat) = 1.7 +/- 0.3 s(-1), K(m) = 1.5 +/- 0.9 microM, and K(i) = 1.9 +/- 0.3). CPR-supported d-Trp oxidations (+/-cytochrome b(5)) exhibit Michaelis-Menten kinetics. Addition of methylene blue (minus ascorbate) to CPR-supported reactions resulted in inhibition of d-Trp turnover and modulation of l-Trp kinetics from allosteric to Michaelis-Menten with a concurrent decrease in substrate affinity for IDO. Our data indicate that CPR is capable of supporting IDO activity in vitro and oxidation of tryptophan by IDO displays substrate stereochemistry dependent atypical kinetics which can be modulated by the addition of cytochrome b(5).

  17. Atmospheric polychlorinated biphenyls in Indian cities: Levels, emission sources and toxicity equivalents

    International Nuclear Information System (INIS)

    Chakraborty, Paromita; Zhang, Gan; Eckhardt, Sabine; Li, Jun; Breivik, Knut; Lam, Paul K.S.; Tanabe, Shinsuke; Jones, Kevin C.

    2013-01-01

    Atmospheric concentration of Polychlorinated biphenyls (PCBs) were measured on diurnal basis by active air sampling during Dec 2006 to Feb 2007 in seven major cities from the northern (New Delhi and Agra), eastern (Kolkata), western (Mumbai and Goa) and southern (Chennai and Bangalore) parts of India. Average concentration of Σ 25 PCBs in the Indian atmosphere was 4460 (±2200) pg/m −3 with a dominance of congeners with 4–7 chlorine atoms. Model results (HYSPLIT, FLEXPART) indicate that the source areas are likely confined to local or regional proximity. Results from the FLEXPART model show that existing emission inventories cannot explain the high concentrations observed for PCB-28. Electronic waste, ship breaking activities and dumped solid waste are attributed as the possible sources of PCBs in India. Σ 25 PCB concentrations for each city showed significant linear correlation with Toxicity equivalence (TEQ) and Neurotoxic equivalence (NEQ) values. Highlights: •Unlike decreasing trend of PCBs in United States and European countries, high levels of PCBs remain in the Indian atmosphere. •Existing emission inventories cannot explain the high PCB concentrations in Indian atmosphere. •Electronic waste recycling, ship dismantling and open burning of municipal solid waste are implicated as potential sources. -- Measurement of atmospheric Polychlorinated biphenyls in seven major Indian cities

  18. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake trout (Salvelinus namaycush) from its prey

    Science.gov (United States)

    Madenjian, Charles P.; David, Solomon R.; Rediske, Richard R.; O’Keefe, James P.

    2012-01-01

    Lake trout (Salvelinus namaycush) were fed bloater (Coregonus hoyi) in eight laboratory tanks over a 135-d experiment. At the start of the experiment, four to nine fish in each tank were sacrificed, and the concentrations of 75 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 10 lake trout remaining in each of the eight tanks at the end of the experiment as well as in the bloater fed to the lake trout. Each lake trout was weighed at the start and the end of the experiment, and the amount of food eaten by the lake trout was recorded. Using these measurements, net trophic transfer efficiency (γ) from the bloater to the lake trout in each of the eight tanks was calculated for each of the 75 congeners. Results showed that γ did not vary significantly with the degree of chlorination of the PCB congeners, and γ averaged 0.66 across all congeners. However,γ did show a slight, but significant, decrease as logKOW increased from 6.0 to 8.2. Activity level of the lake trout did not have a significant effect on γ.

  19. Polychlorinated biphenyls and reproductive hormones in female polar bears at Svalbard.

    Science.gov (United States)

    Haave, Marte; Ropstad, Erik; Derocher, Andrew E; Lie, Elisabeth; Dahl, Ellen; Wiig, Øystein; Skaare, Janneche U; Jenssen, Bjørn Munro

    2003-04-01

    High concentrations of polychlorinated biphenyls (PCBs) in polar bears from Svalbard have increased concern for that population's reproductive health. We examined whether there were associations between the plasma concentrations of PCBs and reproductive hormones [progesterone (P4)] and 17 beta-estradiol (E2)] in free-living female polar bears from Svalbard. Concentrations of P4 depended on reproductive status, and concentrations were lowest in females with offspring--females with cubs and females with yearlings. In these females, the P4 concentrations were positively correlated with plasma sigma PCBs (sum of all analyzed polychlorinated biphenyl congeners) concentrations. The sigma PCBs concentrations explained 27% of the variation in the P4 concentrations. There were no correlations between sigma PCBs and E2 and cortisol in any of the groups of polar bears, or between sigma PCBs and P4 in single polar bears. Although the sigma PCBs-P4 relationship in female polar bears with offspring is not evidence per se of a direct cause-effect association, the results indicate that PCBs may affect levels of P4 in polar bear females. There is a clear need to further assess the hormone balance and population health of polar bears at Svalbard.

  20. The associations between the environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk and progression

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Polychlorinated biphenyls(PCBs) are chlorinated biphenyl compounds with wide applications in the industry.In spite of a ban on their production in the late 1970s,PCBs,as a group of POPs,are still persistent and widely spread in the environment,posing potential threats to human health.The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo,animal and epidemiologic studies.Initial investigations indicated higher levels of PCBs in mammary tissues or sera corresponded to the occurrence of breast cancer,but later studies showed no positive association between PCB exposure and breast cancer development.More recent data suggested that the CYP1A1 m2 polymorphisms might add increased risk to the etiology of breast cancer in women with environmental exposure to PCBs.PCBs are implicated in advancing breast cancer progression,and our unpublished data reveals that PCBs activate the ROCK signaling to enhance breast cancer metastasis.Therefore,the correlation between PCB exposure and breast cancer risk warrants further careful investigations.

  1. Enhancing effect of spawning on elimination of a persistent polychlorinated biphenyl from female yellow perch

    International Nuclear Information System (INIS)

    Vodicnik, M.J.; Peterson, R.E.

    1985-01-01

    Distribution and elimination of 2,5,2',5'-tetrachloro[14C]biphenyl (4-CB) were studied for 6 months after exposing sexually mature female yellow perch to the compound in water and transferring them to flowing 4-CB-free water. Perch that were exposed in January spawned in May, and the study was terminated in June. During the first 41/2 months after exposure, the t1/2 for whole-body elimination was 22 weeks, primarily by elimination of 4-CB from the viscera and carcass. During spawning, enhanced elimination (t1/2 less than 0.7 weeks) was due to the voiding of eggs containing 4-CB. After spawning, whole-body elimination returned to a slower rate (t1/2 = 16.3 weeks). Prior to the enhancement in 4-CB elimination rate during spawning, there was a redistribution of 4-CB residues within the body of the perch which was characterized by a transfer of 4-CB residues from primarily the carcass and viscera to eggs. Two weeks after exposure, 30% of the initial 4-CB body burden was distributed to the eggs, whereas just prior to spawning, about 50% was present in this tissue. These findings demonstrate that egg maturation and spawning result in a significant reduction in the body burden of a persistent polychlorinated biphenyl in a lean-fish species

  2. Polychlorinated biphenyls in surface soil in urban and background areas of Mongolia

    International Nuclear Information System (INIS)

    Mamontova, Elena A.; Mamontov, Alexander A.; Tarasova, Eugenia N.; Kuzmin, Mikhail I.; Ganchimeg, Darmaa; Khomutova, Marina Yu.; Gombosuren, Odontuya; Ganjuurjav, Erdenebayasgalan

    2013-01-01

    Polychlorinated biphenyls (PCBs) were measured in soil in some industrial towns (Ulaanbaatar, Suhbaatar, Erdenet, Darhan, Tsetserleg, Hovd, Ulaangom, Altay, Bayanhongor, Arvayheer, Saynshand, Choybalsan) and in background and rural areas of Mongolia. The average sum of all investigated PCB congeners in soil of Mongolia comes to 7.4 ng/g dry weight (DW) and varies from 0.53 ng/g DW till 114 ng/g DW. PCB levels in soil from towns are significantly higher than those in soil from background and rural areas. The PCB homological composition in soil sampled in highly-PCB-polluted sites is similar to the PCB homological pattern in Sovol and Aroclor 1254. Significant correlation between soil organic carbon and low chlorinated PCB both for towns and background sites was found. Significant differences in PCB means in soil in different natural zones were found. -- Highlights: •First study to measure PCBs in surface soil sampled throughout Mongolia. •The PCB patterns in polluted soil were similar to those in Sovol or Aroclor 1254. •Significant differences in PCB means in soil in different natural zones were found. -- Polychlorinated biphenyls were measured in soils throughout Mongolia

  3. Design, Synthesis, and Herbicidal Activity of Pyrimidine-Biphenyl Hybrids as Novel Acetohydroxyacid Synthase Inhibitors.

    Science.gov (United States)

    Li, Ke-Jian; Qu, Ren-Yu; Liu, Yu-Chao; Yang, Jing-Fang; Devendar, Ponnam; Chen, Qiong; Niu, Cong-Wei; Xi, Zhen; Yang, Guang-Fu

    2018-04-18

    The issue of weed resistance to acetohydroxyacid synthase (EC 2.2.1.6, AHAS) inhibitors has become one of the largest obstacles for the application of this class of herbicides. In a continuing effort to discover novel AHAS inhibitors to overcome weed resistance, a series of pyrimidine-biphenyl hybrids (4aa-bb and 5aa-ah) were designed and synthesized via a scaffold hopping strategy. Among these derivatives, compounds 4aa ( K i = 0.09 μM) and 4bb ( K i = 0.02 μM) displayed higher inhibitory activities against Arabidopsis thaliana AHAS than those of the controls bispyribac ( K i = 0.54 μM) and flumetsulam ( K i = 0.38 μM). Remarkably, compounds 4aa, 4bb, 5ah, and 5ag exhibited excellent postemergence herbicidal activity and a broad spectrum of weed control at application rates of 37.5-150 g of active ingredient (ai)/ha. Furthermore, 4aa and 4bb showed higher herbicidal activity against AHAS inhibitor-resistant Descurainia sophia, Ammannia arenaria, and the corresponding sensitive weeds than that of bispyribac at 0.94-0.235 g ai/ha. Therefore, the pyrimidine-biphenyl motif and lead compounds 4aa and 4bb have great potential for the discovery of novel AHAS inhibitors to combat AHAS-inhibiting herbicide-resistant weeds.

  4. Azo biphenyl polyurethane: Preparation, characterization and application for optical waveguide switch

    Science.gov (United States)

    Jiang, Yan; Da, Zulin; Qiu, Fengxian; Yang, Dongya; Guan, Yijun; Cao, Guorong

    2018-01-01

    Azo waveguide polymers are of particular interest in the design of materials for applications in optical switch. The aim of this contribution was the synthesis and thermo-optic waveguide switch properties of azo biphenyl polyurethanes. A series of monomers and azo biphenyl polyurethanes (Azo BPU1 and Azo BPU2) were synthesized and characterized by FT-IR, UV-Vis spectroscopy and 1H NMR. The physical and mechanical properties of thin polymer films were measured. The refractive index and thermo-optic coefficient (dn/dT) of polymer films were investigated for TE (transversal electric) polarizations by ATR technique. The transmission loss of film was measured using the Charge Coupled Device digital imaging devices. The results showed the Azo BPU2 containing chiral azobenzene chromophore had higher dn/dT and lower transmission loss. Subsequently, a 1 × 2 Y-branch and 2 × 2 Mach-Zehnder optical switches based on the prepared polymers were designed and simulated. The results showed that the power consumption of all switches was less than 1.0 mW. Compared with 1 × 2 Y-branch optical switch, the 2 × 2 Mach-Zehnder optical switches based on the same polymer have the faster response time, which were about only 1.2 and 2.0 ms, respectively.

  5. Hydroxy and methylsulfone metabolites of polychlorinated biphenyls in the human blood and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, Yoshito; Haraguchi, Koichi [Daiichi College of Pharmaceutical Sciences, Fukuoka (Japan)

    2004-09-15

    Polychlorinated biphenyls (PCBs) are a group of chlorinated compounds which have polluted the global environment, persistently retained in wildlife and humans, and eventually affected the human health. PCBs are biotransformed to mainly hydroxy (HO-) and methylsulfone (MeSO{sub 2}-) metabolites in the animal and human tissues. About ten thousands of chemical and biological researches on PCBs, HOPCBs and MeSO{sub 2}-PCBs have been reported and reviewed so far. Letcher et al. cleverly reviewed the HO-PCBs and MeSO2-PCBs in 2000. We review the contamination of HO-PCBs and MeSO{sub 2}-PCBs in human tissues and their possible effects to human health. Different positional numberings of Cl-, HO- and MeSO{sub 2}- on biphenyl rings were used by different authors. Then, nomenclature of PCB metabolite was assessed by Maervoet et al. and they suggested to use the IUPAC chemical name and number of parent PCB congener with the subsequent assignment of the phenyl ring position number of the HO- or MeSO{sub 2}- substituent number afterward.

  6. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  7. Determination of levels of polychlorinated biphenyls (PCBs) present in caulk and window glazing material samples from older buildings

    Science.gov (United States)

    Levels of polychlorinated biphenyls (PCBs) in caulk and window glazing material samples from older buildings were determined, using a method developed for this purpose. This method was evaluated by analyzing a combination of 47 samples of caulk, glazing materials, including quali...

  8. Mixed function oxidase dependent biotransformation of polychlorinated biphenyls by different species of fish from the North Sea

    DEFF Research Database (Denmark)

    Mehrtens, G.; Laturnus, F.

    1999-01-01

    Mixed function oxidase (MFO) dependent biotransformation of polychlorinated biphenyls (PCBs) was measured in three different fish species from the North Sea. Liver microsomes of plaice (Pleuronectes platessa), dab (Limanda limanda) and cod (Gadus morhua) were isolated and incubated with different....... Biotransformations were also species dependent. The flatfish dab and plaice exhibited higher metabolic rates than cod (C) 1999 Elsevier Science Ltd. All rights reserved....

  9. Hydrogen–Hydrogen Bonding in Planar Biphenyl, Predicted by Atoms-In-Molecules Theory, Does Not Exist

    NARCIS (Netherlands)

    Poater, J; Sola, M.; Bickelhaupt, F.M.

    2006-01-01

    Based on an Atoms-in-Molecules (AIM) analysis, Matta et al. (Chem. Eur. J.2003, 9, 1940) recently claimed evidence for the existence of hydrogen–hydrogen bonding between ortho-hydrogen atoms, pointing towards each other from adjacent phenyl groups in planar biphenyl. This AIM result is opposed to

  10. Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and biphenyls (PCBs) in home-produced eggs

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.; Dam, ten G.; Bruggen, van Mark; Jeurissen, Suzanne; Leeuwen, van S.P.J.; Theelen, R.M.C.; Zeilmaker, M.J.

    2016-01-01

    Home produced eggs from 62 addresses in the Netherlands were investigated for the levels of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs), both dioxin-like (dl) and non-dioxin-like (ndl). Compared to commercial eggs, levels were relatively high with a median of 4.6

  11. A SIMPLE AND FAST EXTRACTION METHOD FOR ORGANOCHLORINE PESTICIDES AND POLYCHLORINATED BIPHENYLS IN SMALL VOLUMES OF AVIAN SERUM

    Science.gov (United States)

    A solid-phase extraction (SPE) method was developed using 8 M urea to desorb and extract organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs) from avian serum for analysis by capillary gas chromatography with electron capture detection (GC-ECD). The analytes were ...

  12. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and a polybrominated biphenyl (PBB) in men from Greenland, Poland and Ukraine

    DEFF Research Database (Denmark)

    Lenters, Virissa; Thomsen, Cathrine; Smit, Lidwien A M

    2013-01-01

    in Inuit men from across Greenland, and in men from Warsaw, Poland and Kharkiv, Ukraine. Serum was sampled between 2002 and 2004 from men 19 to 50years of age. 299 samples were analyzed for BDE-28, 47, 99, 100, 153, 154 and 183 and the brominated biphenyl BB-153 using gas chromatography-high resolution...

  13. 21 CFR 509.15 - Use of polychlorinated biphenyls (PCB's) in establishments manufacturing food-packaging materials.

    Science.gov (United States)

    2010-04-01

    ... establishments manufacturing food-packaging materials. 509.15 Section 509.15 Food and Drugs FOOD AND DRUG... polychlorinated biphenyls (PCB's) in establishments manufacturing food-packaging materials. (a) Polychlorinated...). These accidents in turn caused the contamination of food products intended for human consumption (meat...

  14. 21 CFR 109.15 - Use of polychlorinated biphenyls (PCB's) in establishments manufacturing food-packaging materials.

    Science.gov (United States)

    2010-04-01

    ... establishments manufacturing food-packaging materials. 109.15 Section 109.15 Food and Drugs FOOD AND DRUG... polychlorinated biphenyls (PCB's) in establishments manufacturing food-packaging materials. (a) Polychlorinated...). These accidents in turn caused the contamination of food products intended for human consumption (meat...

  15. 77 FR 12836 - Draft Toxicological Review of Biphenyl: In Support of Summary Information on the Integrated Risk...

    Science.gov (United States)

    2012-03-02

    ... the draft human health assessment titled, ``Toxicological Review of Biphenyl: In Support of Summary... email: [email protected] . SUPPLEMENTARY INFORMATION: EPA's IRIS is a human health assessment... exposure to chemical substances found in the environment. Through the IRIS Program, EPA provides the...

  16. Proof of concept for the use of macroinvertebrates as indicators of polychlorinated biphenyls (PCB) contamination in Lake Hartwell

    Science.gov (United States)

    James M. Lazorchak; Michael B. Griffith; Marc Mills; Joseph Schubauer-Berigan; Frank McCormick; Richard Brenner; Craig Zeller

    2015-01-01

    The US Environmental Protection Agency (USEPA) develops methods and tools for evaluating risk management strategies for sediments contaminated with polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and other legacy pollutants. Monitored natural recovery is a risk management alternative that relies on existing physical, chemical, and biological...

  17. Environmental exposure to polychlorinated biphenyls (PCBs) and dioxins - Consequences for longterm neurological and cognitive development of the child. A Review

    NARCIS (Netherlands)

    Boersma, ER

    2001-01-01

    Polychlorinated biphenyl's (PCBs) and dioxins are environmental pollutants. Calculated on a body weight basis, prenatally as well as postnatally through breast-feeding, large amounts are transferred from mother to the child. Formula is free of these substances. Considering their potential

  18. Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age

    NARCIS (Netherlands)

    Patandin, S; Lanting, Caren; Mulder, PGH; Boersma, ER; Sauer, PJJ; Weisglas-Kuperus, N

    Objective: To study possible adverse effects of environmental exposure to polychlorinated biphenyls (PCB) and dioxins on cognitive functioning in young children. Methods: In a follow-up of the Dutch PCB/Dioxin study, cognitive abilities were assessed with the Kaufman Assessment Battery for Children

  19. First worldwide UNEP interlaboratory study on persistent organic pollutants (POPs) with data on polychlorinated biphenyls and organochlorine pesticides

    NARCIS (Netherlands)

    Leeuwen, van S.P.J.; Bavel, van B.; Boer, de J.

    2013-01-01

    The first worldwide interlaboratory study on persistent organic pollutants (POPs) under the Stockholm Convention was organized, with a participation of 103 laboratories from Asia, Europe, the Americas, Africa and Australia, of which the majority submitted data on polychlorinated biphenyls (PCBs) and

  20. Polychlorinated biphenyls, glycaemia and diabetes in a population living in a highly polychlorinated biphenyls-polluted area in northern Italy: a cross-sectional and cohort study

    Directory of Open Access Journals (Sweden)

    Claudia Zani

    2013-05-01

    Full Text Available Background. Polychlorinated biphenyls (PCBs have been found to be associated with diabetes in some, but not all, studies performed so far. The aim of this study was to assess the association between PCB serum levels and glycaemia and diabetes in people living in Brescia, a highly industrialised PCB-polluted town in Northern Italy. Design and Methods. 527 subjects were enrolled in a cross-sectional population-based study: they were interviewed face-to-face in 2003 and also provided a blood sample under fasting conditions. The concentration of 24 PCB congeners was determined using gas-chromatography (GC/MS. Subsequently, all subjects were included in a follow-up (cohort study. According to the Local Health Authority health-care database, subjects were considered to be diabetic if they had diabetes at interview time (prevalent cases or during a 7-year follow-up (incident cases. Results. A total of 53 subjects (10.0% were diabetics: 28 had dia- betes at enrolment and other 25 developed the disease subsequently. Diabetes frequency increased according to the serum concentrations of total PCBs and single PCB congeners, but no association was found when estimates were adjusted for education, body mass index, age and gender by logistic regression analysis. Accordingly, glycaemia increased with PCB serum levels, but no association was observed when multiple regression analysis, including confounding factors, was performed. Conclusions. This study does not support the hypothesis that PCB environmental exposure is strictly associated with diabetes or glycaemia.

  1. Synthesis and characterization of tissue-retainable methylsulfonyl polychlorinated biphenyl isomers

    International Nuclear Information System (INIS)

    Haraguchi, K.; Kuroki, H.; Masuda, Y.

    1987-01-01

    Eighty-six positional isomers of methylsulfonyl polychlorinated biphenyls (MSF-PCBs) have been synthesized by three synthetic routes: (1) the diazo coupling reaction of 3-(methylsulfonyl)chloroaniline with chlorobenzene; (2) nucleophilic substitution of PCB with methanethiolate and successive oxidation of the corresponding methyl sulfide; (3) the diazo coupling reaction of chloroaniline with chlorothioanisole and successive oxidation of the methyl sulfide. Pure isomers were characterized by their proton magnetic resonance and mass spectra and used to unambiguously identify the MSF metabolites retained in human tissues by using high-resolution capillary gas chromatography (GC). The GC analysis showed that 40 MSF derivatives were positively identified in the tissue of a patient with Yusho on the basis of comparisons of their GC retention data with those of the standard compounds

  2. Distribution characteristics of polychlorinated biphenyls (PCBs) in coastal areas of Okinawa Island, Japan

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Surface sediment and seawater samples were collected from coastal areas around Okinawa Island from September 2001 to May 2002. The samples were analyzed for total polychlorinated biphenyl (PCB) levels and homolog composition. The results show that total PCB levels ranged from 0.32 to 128.7 ng/g (dry wt.) in sediment and 1.59 to 2.48 ng/L in seawater. The levels exceed the Environmental Quality Standard (EQS) for water pollution of Japan. The distribution of PCB homolog showed different patterns in the sediments and seawaters. Penta-chlorobiphenyls (CBs) comprised the main congener group in seawater, while hexa-CBs were more abundant homologs in the sediments. The heavily contaminated sites featured higher CBs, including penta-CBs, hexa-CBs, and hepta-CBs, than those in less contaminated sites where tri-CBs dominated. This study provides current distribution and geochemical behavior of PCBs in the coastal areas around Okinawa Island.

  3. Final report for Tank 100 Sump sludge (KON332) for polychlorinated biphenyl's (PCB)

    International Nuclear Information System (INIS)

    Fuller, R.K.

    1998-01-01

    Final Report for Tank 100 Sump Sludge (KON332) for Polychlorinated Biphenyl's (PCB) Sample Receipt Sample KON332 was received from Tank 100-Sump (WESF) on May 18, 1998. The laboratory number issued for this sample is S98BOO0207 as shown on the Request for Sample Analysis (RSA) form (Attachment 4). The sample breakdown diagram (Attachment 3) provides a cross-reference of customer sample identification to the laboratory identification number. Attachment 4 provides copies of the Request for Sample Analysis (RSA) and Chain of Custody (COC) forms. The sample was received in the laboratory in a 125-ml polybottle. Breakdown and subsampling was performed on June 6, 1998. PCB analysis was performed on the wet sludge. A discussion of the results is presented in Attachment 2. The 222-S extraction bench sheets are presented in Attachment 5. The PCB raw data are presented in Attachment 6

  4. Polychlorinated biphenyls (PCBs) in recreational marina sediments of San Diego Bay, southern California.

    Science.gov (United States)

    Neira, Carlos; Vales, Melissa; Mendoza, Guillermo; Hoh, Eunha; Levin, Lisa A

    2018-01-01

    Polychlorinated biphenyl (PCB) concentrations were determined in surface sediments from three recreational marinas in San Diego Bay, California. Total PCB concentrations ranged from 23 to 153, 31-294, and 151-1387ngg -1 for Shelter Island Yacht Basin (SIYB), Harbor Island West (HW) and Harbor Island East (HE), respectively. PCB concentrations were significantly higher in HE and PCB group composition differed relative to HW and SIYB, which were not significantly different from each other in concentration or group composition. In marina sediments there was a predominance (82-85%) of heavier molecular weight PCBs with homologous groups (6CL-7CL) comprising 59% of the total. In HE 75% of the sites exceeded the effect range median (ERM), and toxicity equivalence (TEQ dioxin-like PCBs) values were higher relative to those of HW and SIYB, suggesting a potential ecotoxicological risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. (Biphenyl-4-yl)methylammonium chlorides: potent anticonvulsants that modulate Na+ currents.

    Science.gov (United States)

    Lee, Hyosung; Park, Ki Duk; Yang, Xiao-Fang; Dustrude, Erik T; Wilson, Sarah M; Khanna, Rajesh; Kohn, Harold

    2013-07-25

    We have reported that compounds containing a biaryl linked unit (Ar-X-Ar') modulated Na(+) currents by promoting slow inactivation and fast inactivation processes and by inducing frequency (use)-dependent inhibition of Na(+) currents. These electrophysiological properties have been associated with the mode of action of several antiepileptic drugs. In this study, we demonstrate that the readily accessible (biphenyl-4-yl)methylammonium chlorides (compound class B) exhibited a broad range of anticonvulsant activities in animal models, and in the maximal electroshock seizure test the activity of (3'-trifluoromethoxybiphenyl-4-yl)methylammonium chloride (8) exceeded that of phenobarbital and phenytoin upon oral administration to rats. Electrophysiological studies of 8 using mouse catecholamine A-differentiated cells and rat embryonic cortical neurons confirmed that 8 promoted slow and fast inactivation in both cell types but did not affect the frequency (use)-dependent block of Na(+) currents.

  6. Problems with the polychlorinated biphenyls (PCB) in Mexico; Problematica de los bifenilos policlorados (BPC) en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Valle, Esteban; Cruz, Maria Guadalupe [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1997-12-31

    A general overview is presented of the problems with the polychlorinated biphenyls (PCB) (askarels) in Mexico, which are mainly associated with the use of these substances in electric equipment; also, a profile of the causes why the PCBs have been classified as environmental toxic substances and a potential hazard for the health of human beings. [Espanol] Se presenta un panorama general de la problematica de bifenilos policlorados (BPC) (askareles) en Mexico, la cual esta asociada principalmente con el uso de estos compuestos en equipos electricos; asimismo, se describe una semblanza de las causas por las cuales se han catalogado a los BPC como sustancias toxicas ambientales y un peligro potencial para la salud de los seres humanos.

  7. Partitioning of naphthalene, methylnaphthalenes and biphenyl between wastewater treatment sludges and water

    International Nuclear Information System (INIS)

    Southworth, G.R.; Keller, J.L.

    1984-01-01

    Partition coefficients (K/sub p/) describing the partitioning of naphthalene, methylnaphthalenes and biphenyl between organic-rich wastes and water were determined using 14 C-tracer techniques as well as high performance liquid chromatographic analysis of the wastes and their aqueous extracts. Results of the two procedures were in good agreement. The concentrations of the specific organics in the wastes were not good predictors of concentrations in aqueous extracts, since K/sub p/ varied among the materials tested. Predictions of k/sub p/ based on organic carbon content of the sludges were well below observed values. Oil content of the wastes and oil-water partition coefficients appeared to be important factors in determining K/sub p/. 11 references, 5 tables

  8. Secondary sex ratio in relation to exposures to polychlorinated biphenyls, dichlorodiphenyl dichloroethylene and methylmercury

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Choi, Anna L.; Petersen, Maria Skaalum

    2017-01-01

    This study was undertaken to assess the potential impact of maternal exposures to polychlorinated biphenyl (PCB), dichlorodiphenyl dichloroethylene (DDE) and methylmercury on the secondary sex ratios (the ratio of male to female live births) over a span of 23 years. The study includes prospective...... data from three Faroese birth cohorts, with a total of 2,152 healthy mother-child dyads recruited between 1986 and 2009. The Faroe Islands is a subarctic fishing community, where pilot whale meat and blubber are part of the traditional marine diet. Exposures were measured in maternal hair, serum...... or umbilical cord blood. Confounder adjusted logistic regression models were used to assess the associations between maternal exposures and the secondary sex ratio. A doubling in ΣPCB, p,p'-DDE and mercury concentrations were associated with increased odds by 8% (95% CI = 0-16%), 7% (95% CI = 0-14%) and 9% (95...

  9. Polychlorinated biphenyl concentrations in adipose tissue and abdominal obesity in the elderly

    DEFF Research Database (Denmark)

    Bräuner, Elvira; Raaschou-Nielsen, Ole; Andersen, Zorana

    2013-01-01

    Obesity prevalence has more than doubled globally within the last 30 years. Obesity affects quality of life as well as impacts the risks and prognosis for a number of serious diseases. Established causes include a high calorie diet combined with a sedentary lifestyle and possibly the widespread...... cessation of smoking, but these do not fully explain the epidemic. Polychlorinated biphenyl congeners (PCBs) are endocrine-disrupting chemicals and evidence from animal experiments suggests an association with obesity development. Our knowledge of the effects of these compounds on weight gain in humans...... is limited. Our objective was to investigate the association between exposure to PCBs experienced by a general Danish population and development of obesity. We randomly selected 204 persons (113 obese and 91 overweight), aged ≥ 50 years, from a prospective Danish cohort of 57,053 persons and examined ten...

  10. Solid phase extraction of polychlorinated biphenyls from water containing humic substances

    Energy Technology Data Exchange (ETDEWEB)

    Bonifazi, P.; Pierini, E.; Bruner, F. [Centro di Studio per la Chimica dell`Ambiente e le Tecnologie Strumentali Avanzate dell` Universita degli Studi di Urbino, Ist. di Scienze Chimiche (Italy)

    1997-06-01

    A study was carried out of the recovery by solid phase extraction of the eleven most toxic polychlorinated biphenyls from water containing humic acids. Experiments were performed using water polluted with a humic acid (sodium salt) concentration of 9-18 mg L{sup -1}. The effect of humic acids on the recoveries was noticeable, especially where the more chlorinated congeners were concerned. The effect was also evident with river water containing naturally dissolved humic acids. A method for destroying humic acids prior to extraction was applied. The recoveries after the destruction of humic acids were in the range of 90%, even in the case of river water, demonstrating the applicability of the method to real samples. (orig.)

  11. Problems with the polychlorinated biphenyls (PCB) in Mexico; Problematica de los bifenilos policlorados (BPC) en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Valle, Esteban; Cruz, Maria Guadalupe [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1998-12-31

    A general overview is presented of the problems with the polychlorinated biphenyls (PCB) (askarels) in Mexico, which are mainly associated with the use of these substances in electric equipment; also, a profile of the causes why the PCBs have been classified as environmental toxic substances and a potential hazard for the health of human beings. [Espanol] Se presenta un panorama general de la problematica de bifenilos policlorados (BPC) (askareles) en Mexico, la cual esta asociada principalmente con el uso de estos compuestos en equipos electricos; asimismo, se describe una semblanza de las causas por las cuales se han catalogado a los BPC como sustancias toxicas ambientales y un peligro potencial para la salud de los seres humanos.

  12. Migration of CT triplet excitons in TCNB-biphenyl and TCNB-HMB crystals

    Science.gov (United States)

    Kozankiewicz, BolesAw

    1994-01-01

    Delayed fluorescence decay curves of charge transfer (CT) crystals of tetracyanobenzene with biphenyl (TCNB-B) and with hexamethylbenzene (TCNB-HMB) have been studied over a wide temperature range (5-200 K). The decay curves have been adequately described by decay expressions derived for different mechanisms of triplet-triplet annihilation. This analysis points to one-dimensional, thermally activated motion of CT triplet excitons. The estimated activation energies for the exciton hopping are 360±60 and 650±100 cm -1 (or 550±150 cm -1 depending on the applied model) for the TCNB-B and TCNB-HMB crystals, respectively. The results seem to confirm the self-trapping of triplet CT excitons.

  13. [Indoor air pollution by polychlorinated biphenyl compounds in permanently elastic sealants].

    Science.gov (United States)

    Burkhardt, U; Bork, M; Balfanz, E; Leidel, J

    1990-10-01

    A common cause for indoor pollution by polycholorinated biphenyls (PCB) are defective capacitors of luminous discharge lamps. This paper describes elastic sealing compounds as another source of PCB pollution in buildings. In several rooms of a large school building indoor concentrations of 1000 ng PCB/m3 and more were registered. The total PCB concentration in sealing compounds ranged between 124,000 and 327,000 ppm. Blood specimens drawn from the school's personnel did not show elevated PCB concentrations, but additional incorporation of PCB via the respiratory tract cannot be excluded. We do not presume that any impairment of the health has been caused by this pollutant, but we think that reduction of the PCB indoor concentrations would be advisable for prophylactic purposes. Attention should be given to so-called open PCB systems such as elastic sealing compounds. Although they have been prohibited 1978, there might be a widespread use in older buildings.

  14. Di-tert-butyl 2,2′-(biphenyl-2,2′-diyldioxydiacetate

    Directory of Open Access Journals (Sweden)

    Qamar Ali

    2008-08-01

    Full Text Available The title compound, C24H30O6, does not exhibit π–π interactions due to the steric effect of the bulky tert-butyl groups present in the molecule. The presence of these groups at the 2 and 2′ positions hinders the free motion of the benzene rings relative to each other, causing them to adopt an antiperiplanar arrangement. The benzene rings are twisted by just under 50.96 (17° with respect to each other. The carbonyl groups within the molecule are directed in different directions, one towards the biphenyl group and the other away from it. The molecules are linked together by C=O...H—C hydrogen bonds.

  15. Dioxins, furans, and polychlorinated biphenyls in hen eggs – a new source of hazard for consumers?

    Directory of Open Access Journals (Sweden)

    Piskorska-Pliszczyńska Jadwiga

    2015-12-01

    Full Text Available The paper presents the results of testing eggs for the content of dioxins and polychlorinated biphenyls (PCBs, determination of the sources that caused the presence of high concentrations of these compounds which exceeded the acceptable contamination levels, and assessment of consumer health risk caused by the consumption of eggs with excessive contents of investigated compounds. In about 9% of free range eggs and 17% of organic eggs, the content of PCDD/Fs was two- or threefold higher than the acceptable limits, and in some samples the concentration of investigated compounds exceeded the maximum concentration levels. Based on the profile of the compounds, it was confirmed in several cases that their main source was the soil or unsecured refuse. The consumers of eggs and meat produced under these conditions constitute the risk groups, and their dioxin and PCB intake may exceed toxicological reference values.

  16. Intergenerational effects of endocrine-disrupting compounds: a review of the Michigan polybrominated biphenyl registry.

    Science.gov (United States)

    Curtis, Sarah W; Conneely, Karen N; Marder, Mary E; Terrell, Metrecia L; Marcus, Michele; Smith, Alicia K

    2018-06-11

    Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

  17. Organochlorine Pesticides (OCs) and Polychlorinated Biphenyls (PCBs) in Tilapia zillii from Lake El-Manzala, Egypt

    International Nuclear Information System (INIS)

    El-Greisy, Zeinab Abdalbagi; Abdallah, A. Mohamed Ali

    2005-01-01

    A fresh water fish species, (Tilapia zillii) from Lake El-Manzala was analyzed for concentrations of several Organochlorine pesticides (OCs) and Polychlorine piphenyl's (PCBs) in liver, gonads, mesenteric fat, flesh and the digestive tract in mature fish during the breeding season. Polychlorinated piphenyls (PCBs) and Organochloripe pesticides (OCs) were calculated in (ng/g) dry weight (dw) in homogenized samples. The obtained results revealed differences in lipid content between these different organs. The females showed higher lipid content than males. There was significant positive correlation the lipid content and organochlorines and polychlorinated biphenyls (PCBs). The results come concomitant with the lipophilicity of studied compounds. However, the recoded concentration of these studied pollutants still does not exceed international hazardous levels. (author)

  18. Persistent organochlorine residues and toxic evaluation of polychlorinated biphenyls in sharks from the Mediterranean Sea (Italy)

    Energy Technology Data Exchange (ETDEWEB)

    Storelli, M.M.; Marcotrigiano, G.O. [Bari Univ., Dip. Farmaco-Biologico, Bari (Italy)

    2001-07-01

    Persistent organochlorines such as polychlorinated biphenyls including coplanar congeners, DDT compounds and HCB were measured in different tissues (muscle, liver and eggs) of two Mediterranean shark species: namely Centrophorus granulosus and Squalus blainvillei. The concentrations of organochlorines in the tissues and organs of both species were in the order DDTs>PCBs>HCB. The highest values of DDTs, PCBs and HCB were found in liver followed by eggs and muscle. Among DDTs the compound found in greatest concentration was p,p -DDE. The PCB profiles were dominated by congeners 138, 153, and 180. The isomers with higher TEQs values were non- and mono-ortho congeners than di-ortho ones in muscle, liver and eggs of both species. Among the non-ortho, PCB 126 was the major contributing individual to the total TEQs in both species. (Author)

  19. Temporal Trends of Hexabromocyclododecane, Polybrominated Diphenyl Ethers and Polychlorinated Biphenyls in Ringed Seals from East Greenland

    DEFF Research Database (Denmark)

    Vorkamp, Katrin; Riget, Frank Farsø; Bossi, Rossana

    2011-01-01

    also was found for adult seals with a time trend starting in 1994. ΣPCB decreased significantly in juvenile seals, again due to the 1986 value, while no trend was found for the adult animals. This indicates stagnating PCB concentrations at a relatively high level, in some cases possibly exceeding......Concentrations of hexabromocyclododecane (HBCD) were determined in a combination of archived and fresh blubber samples of juvenile ringed seals from East Greenland collected between 1986 and 2008. R-HBCD was the only diastereoisomer consistently above levels of quantification and showed...... on polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) have been extended with new data for 2006 and 2008. ΣPBDE in juvenile seals was the only parameter with a slight upward trend, however, dependent on the low 1986 concentration. Removing this data point resulted in a downward trend, which...

  20. Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain

    DEFF Research Database (Denmark)

    Malkiewicz, Katarzyna; Mohammed, Roma; Folkesson, Ronnie

    2006-01-01

    Polychlorinated Biphenyls (PCBs)-induced changes in synaptic transmission are one of the effects of their neurotoxicity but the mechanism remains unknown. We assessed the in vivo effects of the PCBs mixture, Aroclor 1254 on the expression of neuronal proteins that are involved in the synaptic...... function and/or are associated with neurodegeneration. Wistar rats were treated orally with repeated doses of Aroclor 1254 and the levels of soluble alpha-synuclein, parkin, synaptophysin and amyloid precursor protein (APP) in the brain were determined by Western blotting. The results showed that Aroclor...... did not cause changes in the expression and processing of APP but at a dose 100 microg/g/day repeated for 6 days caused a decrease in the expression of alpha-synuclein in the cerebellum, cortex, hippocampus and hypothalamus of the animals sacrificed 2 days after treatment. The decrease in alpha...

  1. Tissue deposition of polychlorinated biphenyls in cats fed Atlantic Ocean bluefish.

    Science.gov (United States)

    Carbone, L G; Alo, D K; Scarlett, J M; Gutenmann, W H; Lisk, D J

    1991-07-01

    Bluefish (Pomatomus saltatrix), a very popular marine sport fish caught in Atlantic coastal waters, contain significant levels of polychlorinated biphenyls (PCBs). Since fish can be an appreciable portion of human and feline diets, a feeding study was conducted with cats fed exclusively bluefish for 86 days with determination of tissue concentrations of PCBs. The concentrations of PCBs in brain, liver, and fat were significantly higher (p = 0.01) in the fish-fed cats than in the control group using the Wilcoxon rank sum test. The highest PCB levels were in fat, the median concentrations being 48 and 0.61 ppm (dry weight) in the fish-fed and control cats, respectively. The significance of the results is discussed.

  2. Blarina brevicauda as a biological monitor of polychlorinated biphenyls: evaluation of hepatic cytochrome P450 induction.

    Science.gov (United States)

    Russell, Julie S; Halbrook, Richard S; Woolf, Alan; French, John B; Melancon, Mark J

    2004-08-01

    We assessed the value of short-tailed shrews (Blarina brevicauda) as a possible biomonitor for polychlorinated biphenyl pollution through measurement of the induction of hepatic cytochrome P450 and associated enzyme activities. First, we checked the inducibility of four monooxygenases (benzyloxyresorufin-O-dealkylase [BROD], ethoxyresorufin-O-dealkylase [EROD], methoxyresorufin-O-dealkylase [MROD], and pentoxyresorufin-O-dealkylase [PROD]) by measuring the activity of these enzymes in hepatic microsomes prepared from shrews injected with beta-naphthoflavone (betaNF) or phenobarbital (PB), typical inducers of cytochrome P4501A (CYP1A) and CYP2B enzyme families, respectively. Enzyme activity was induced in shrews that received betaNF but not in shrews that received PB; PROD was not induced by either exposure. Later, shrews were exposed to a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1242:1254, in 1:2 ratio) at 0.6, 9.6, and 150 ppm in food, for 31 d. Induction in these shrews was measured by specific enzyme activity (BROD, EROD, and MROD) in hepatic microsomes, by western blotting of solubilized microsomes against antibodies to CYP1A or CYP2B, and by duration of sodium pentobarbital-induced sleep. These three CYP enzymes were induced in shrews by PCBs at similar levels of exposure as in cotton rat (Sigmodon hispidus). Neither sleep time nor the amount of CYP2B family protein were affected by PCB exposure. Blarina brevicauda can be a useful biomonitor of PCBs that induce CYP1A, especially in habitats where they are the abundant small mammal.

  3. Sex dependence of the components and structure of urinary calculi induced by biphenyl administration in rats.

    Science.gov (United States)

    Ohnishi, M; Yajima, H; Yamamoto, S; Matsushima, T; Ishii, T

    2000-08-01

    To obtain definitive information about the mechanisms of urinary calculus formation and the structural characteristics of the calculi induced by biphenyl administration in rats, with a focus on the sex dependency, the constituents of the urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (ICP), micro Fourier transform infrared spectroscopy (mFT-IR), and ion chromatography (IC), and structural analyses were carried out by microscopy, mFT-IR, and the electron probe microanalyzer (EPMA) method. We attempted to account for the appreciably higher incidence of calculi in males than in females. mFT-IR analysis revealed that the biphenyl-induced urinary calculi in male rats are composed mainly of potassium 4-hydroxybiphenyl-o-sulfate (4-HBPOSK), whereas the calculi in female rats are composed mainly of 4-hydroxybiphenyl (4-HBP) and KHSO(4) produced by the hydrolysis of 4-HBPOSK. Observations of photomicrographs and the results of mFT-IR analysis indicated that the calculi in males have a multilayer structure consisting of alternating layers of 4-HBPOSK and calcium phosphate, whereas the calculi in females have no multilayer structure, but open holes in which needle-shaped crystals are present in some places. In view of the results of these analyses, including the EPMA analysis, it appears that calculus formation in males may involve a series of successive and irreversible reactions, whereas calculus formation in females may result from a series of reversible reactions, including the hydrolysis of 4-HBPOSK. It was inferred that the series of irreversible reactions involved in calculus formation in males is relatively more stable than that in the case of females, and thus, a sex difference in the reaction features may be responsible for the observed difference in the incidence of calculus formation.

  4. Assessment of polychlorinated biphenyls and organochlorine pesticides in water samples from the Yamuna River

    Directory of Open Access Journals (Sweden)

    Bhupander Kumar

    2012-07-01

    Full Text Available Polychlorinated biphenyls (PCBs, hexachlorocyclohexane (HCH and dichlorodiphenyltrichloroethane (DDT are toxic, persistent and bioaccumulative long-range atmospheric transport pollutants. These are transported worldwide affecting remote regions far from their original sources, and can transfer into food webs with a wide range of acute and chronic health effects. India ratified the Stockholm Convention with the intention of reducing and eliminating persistent organic pollutants (POPs, and encouraged the support of research on POPs. Despite the ban and restriction on the use of these chemicals in India, their contamination of air, water, sediment, biota and humans has been reported. In this study, surface water samples were collected during January 2012 from the Yamuna River in Delhi, India, and analyzed for PCBs and organochlorine pesticides (OCPs. The concentrations of ΣPCBs and ΣOCPs ranged between 2-779 ng L–1 and from less than 0.1 to 618 ng L–1 (mean 99±38 ng L–1 and 221±50 ng L–1, respectively. The PCB homolog was dominated by 3-4 chlorinated biphenyls. In calculating the toxicity equivalent of dioxin-like PCBs (dl-PCBsusing World Health Organization toxic equivalency factors, dl-PCBs accounted for 10% of a total of 27 PCBs. The concentration of ΣHCH ranged between less than 0.1 and 285 ng L–1 (mean 151±32 ng L–1. However, ΣDDTs concentrations varied between less than 0.1 and 354 ng L–1 (mean 83±26 ng L–1. The concentrations were lower than the US guideline values; however, levels of lindane exceeded those recommended in guidelines. Further in-depth study is proposed to determine the bioaccumulation of these pollutants through aquatic biota to assess the risk of contaminants to human health.

  5. Chlorinated hydrocarbon pesticides and polychlorinated biphenyls in sediment cores from San Francisco Bay

    Science.gov (United States)

    Venkatesan, M.I.; De Leon, R. P.; VanGeen, A.; Luoma, S.N.

    1999-01-01

    Sediment cores of known chronology from Richardson and San Pablo Bays in San Francisco Bay, CA, were analyzed for a suite of chlorinated hydrocarbon pesticides and polychlorinated biphenyls to reconstruct a historic record of inputs. Total DDTs (DDT = 2,4'- and 4,4'-dichlorodiphenyltrichloroethane and the metabolites, 2,4'- and 4,4'-DDE, -DDD) range in concentration from 4-21 ng/g and constitute a major fraction (> 84%) of the total pesticides in the top 70 cm of Richardson Bay sediment. A subsurface maximum corresponds to a peak deposition date of 1969-1974. The first measurable DDT levels are found in sediment deposited in the late 1930's. The higher DDT inventory in the San Pablo relative to the Richardson Bay core probably reflects the greater proximity of San Pablo Bay to agricultural activities in the watershed of the Sacramento and San Joaquin rivers. Total polychlorinated biphenyls (PCBs) occur at comparable levels in the two Bays (inventories in San Pablo Bay are about a factor of four higher in the last four decades than in Richardson Bay, suggesting a distribution of inputs not as strongly weighed towards the upper reaches of the estuary as DDTs. The shallower subsurface maximum in PCBs compared to DDT in the San Pablo Bay core is consistent with the imposition of drastic source control measures four these constituents in 1970 and 1977 respectively. The observed decline in DDT and PCB levels towards the surface of both cores is consistent with a dramatic drop in the input of these pollutants once the effect of sediment resuspension and mixing is taken into account.

  6. Production of 10S-hydroxy-8(E)-octadecenoic acid from oleic acid by whole recombinant Escherichia coli cells expressing 10S-dioxygenase from Nostoc punctiforme PCC 73102 with the aid of a chaperone.

    Science.gov (United States)

    Kim, Min-Ji; Seo, Min-Ju; Shin, Kyung-Chul; Oh, Deok-Kun

    2017-01-01

    To increase the production of 10S-hydroxy-8(E)-octadecenoic acid from oleic acid by whole recombinant Escherichia coli cells expressing Nostoc punctiforme 10S-dioxygenase with the aid of a chaperone. The optimal conditions for 10S-hydroxy-8(E)-octadecenoic acid production by recombinant cells co-expressing chaperone plasmid were pH 9, 35 °C, 15 % (v/v) dimethyl sulfoxide, 40 g cells l -1 , and 10 g oleic acid l -1 . Under these conditions, recombinant cells co-expressing chaperone plasmid produced 7.2 g 10S-hydroxy-8(E)-octadecenoic acid l -1 within 30 min, with a conversion yield of 72 % (w/w) and a volumetric productivity of 14.4 g l -1 h -1 . The activity of recombinant cells expressing 10S-dioxygenase was increased by 200 % with the aid of a chaperone, demonstrating the first biotechnological production of 10S-hydroxy-8(E)-octadecenoic acid using recombinant cells expressing 10S-dioxygenase.

  7. Comparison of proposed frameworks for grouping polychlorinated biphenyl congener data applied to a case-control pilot study of prostate cancer

    International Nuclear Information System (INIS)

    Ritchie, Justine M.; Vial, Scott L.; Fuortes, Laurence J.; Robertson, Larry W.; Guo, Haijun; Reedy, Victoria E.; Smith, Elaine M.

    2005-01-01

    Although the commercial synthesis of polychlorinated biphenyls (PCBs) has been banned in the United States for several decades, they are persistent in the environment with exposure mainly being through diet. The biologic and toxic effects of PCBs and their metabolites are due in part to their ability to interact with several cellular and nuclear receptors, thereby altering signaling pathways and gene transcription. These effects include endocrine modulation and disruption. Therefore, the natural history of cancer in tissues expressing these receptors may be modulated by PCB congeners, which are known to have estrogenic, antiestrogenic, and other hormonal effects. Several frameworks for grouping PCB congeners based on these interactions have been proposed. We conducted a hospital-based, case-control pilot study of 58 prostate cancer cases and 99 controls to evaluate the association between the proposed PCB groupings and the risk of prostate cancer. Serum samples were analyzed for a total of 30 PCBs. In multivariate analyses, the odds of prostate cancer among men with the highest concentrations of moderately chlorinated PCBs or PCBs with phenobarbital-like activities (constitutively active receptor (CAR) agonists) was over two times that among men with the lowest concentrations. Increasing trends in risk across the concentration levels were also observed. These results suggest that a higher burden of PCBs that are CAR agonists may be positively associated with an increased risk of prostate cancer and they encourage further research in this area

  8. A cohort study of the association between secondary sex ratio and parental exposure to polybrominated biphenyl (PBB and polychlorinated biphenyl (PCB

    Directory of Open Access Journals (Sweden)

    Terrell Metrecia L

    2009-08-01

    Full Text Available Abstract Background Polybrominated biphenyl (PBB, a brominated flame retardant, was accidently mixed into animal feed in Michigan (1973–1974 resulting in human exposure through consumption of contaminated meat, milk and eggs. Beginning in 1976 individuals who consumed contaminated products were enrolled in the Michigan Long-Term PBB Study. This cohort presents a unique opportunity to study the association between parental exposures to PBB and offspring sex ratio. Methods We identified offspring of female PBB cohort participants (born 1975–1988 and obtained electronic birth records for those born in the state of Michigan. We linked this information to parental serum PBB and PCB concentrations collected at enrollment into the cohort. We modeled the odds of a male birth with generalized estimating equations accounting for the non-independence of siblings born to the same parents. We explored potential confounders: parental age and education at offspring's birth, parental body mass index at cohort enrollment, birth order, gestational age and year of offspring's birth. Results The overall proportion of male offspring among 865 live births to cohort mothers was 0.542. This was higher than the national male proportion of 0.514 (binomial test: p = 0.10. When both parents were in the cohort (n = 300, we found increased odds of a male birth with combined parents' enrollment PBB exposure ≥ the median concentrations (3 μg/L for mothers; 6 μg/L for fathers compared to combined parents' PBB exposure Conclusion This study adds to the body of literature on secondary sex ratio and exposure to environmental contaminants. In this population, combined parental exposure to PBBs or PCBs increased the odds of a male birth. Further research is needed to corroborate these findings and shed light on the biological mechanisms by which these types of chemicals may influence the secondary sex ratio.

  9. Synthesis of 5-hydroxyectoine from ectoine: crystal structure of the non-heme iron(II and 2-oxoglutarate-dependent dioxygenase EctD.

    Directory of Open Access Journals (Sweden)

    Klaus Reuter

    2010-05-01

    Full Text Available As a response to high osmolality, many microorganisms synthesize various types of compatible solutes. These organic osmolytes aid in offsetting the detrimental effects of low water activity on cell physiology. One of these compatible solutes is ectoine. A sub-group of the ectoine producer's enzymatically convert this tetrahydropyrimidine into a hydroxylated derivative, 5-hydroxyectoine. This compound also functions as an effective osmostress protectant and compatible solute but it possesses properties that differ in several aspects from those of ectoine. The enzyme responsible for ectoine hydroxylation (EctD is a member of the non-heme iron(II-containing and 2-oxoglutarate-dependent dioxygenases (EC 1.14.11. These enzymes couple the decarboxylation of 2-oxoglutarate with the formation of a high-energy ferryl-oxo intermediate to catalyze the oxidation of the bound organic substrate. We report here the crystal structure of the ectoine hydroxylase EctD from the moderate halophile Virgibacillus salexigens in complex with Fe(3+ at a resolution of 1.85 A. Like other non-heme iron(II and 2-oxoglutarate dependent dioxygenases, the core of the EctD structure consists of a double-stranded beta-helix forming the main portion of the active-site of the enzyme. The positioning of the iron ligand in the active-site of EctD is mediated by an evolutionarily conserved 2-His-1-carboxylate iron-binding motif. The side chains of the three residues forming this iron-binding site protrude into a deep cavity in the EctD structure that also harbours the 2-oxoglutarate co-substrate-binding site. Database searches revealed a widespread occurrence of EctD-type proteins in members of the Bacteria but only in a single representative of the Archaea, the marine crenarchaeon Nitrosopumilus maritimus. The EctD crystal structure reported here can serve as a template to guide further biochemical and structural studies of this biotechnologically interesting enzyme family.

  10. SIMPLE METHOD FOR ESTIMATING POLYCHLORINATED BIPHENYL CONCENTRATIONS ON SOILS AND SEDIMENTS USING SUBCRITICAL WATER EXTRACTION COUPLED WITH SOLID-PHASE MICROEXTRACTION. (R825368)

    Science.gov (United States)

    A rapid method for estimating polychlorinated biphenyl (PCB) concentrations in contaminated soils and sediments has been developed by coupling static subcritical water extraction with solid-phase microextraction (SPME). Soil, water, and internal standards are placed in a seale...

  11. Synthesis and Screening of Novel Substituted Biphenyl Proteomimetics as Potential Anti-Estrogenic Agents for the Treatment of Hormone-Responsive Breast Cancer

    National Research Council Canada - National Science Library

    Hanson, Robert N

    2005-01-01

    .... The specific aims involved preparing the requisite aryl halide and boronic acid intermediates, coupling to generate the small biphenyl library and evaluating the compounds in a competitive binding assay...

  12. The need and Potential of Biosensors to Detect Dioxins and Dioxin-Like Polychlorinated Biphenyls along the Milk, Eggs and Meat Food Chain

    NARCIS (Netherlands)

    Chobtang, J.; Boer, de I.J.M.; Hoogenboom, L.A.P.; Haasnoot, W.; Kijlstra, A.; Meerburg, B.G.

    2011-01-01

    Dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) are hazardous toxic, ubiquitous and persistent chemical compounds, which can enter the food chain and accumulate up to higher trophic levels. Their determination requires sophisticated methods, expensive facilities and instruments,

  13. Polychlorinated Biphenyls (PCBs) and Polybrominated Diphenol Ethers (PBDEs) in Current and Historical Samples of Avian Eggs from Nesting Sites in Buzzards Bay, MA, USA

    Science.gov (United States)

    We measured concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in eggs from breeding colonies in Buzzards Bay, MA, USA. Eggs from two piscivorous bird species, common (Sterna hirundo) and roseate (Sterna dougallii) terns, were collected...

  14. Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment

    Directory of Open Access Journals (Sweden)

    Jayashree Dolpady

    2016-01-01

    Full Text Available The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA, protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103+ DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.

  15. Umbilical Cord Tissue-Derived Mesenchymal Stem Cells Induce T Lymphocyte Apoptosis and Cell Cycle Arrest by Expression of Indoleamine 2, 3-Dioxygenase

    Directory of Open Access Journals (Sweden)

    Xiuying Li

    2016-01-01

    Full Text Available It has been reported that human mesenchymal stem cells are able to inhibit T lymphocyte activation; however, the discrepancy among different sources of MSCs is not well documented. In this study, we have compared the MSCs from bone marrow (BM, adipose tissue (AT, placenta (PL, and umbilical cord (UC to determine which one displayed the most efficient immunosuppressive effects on phytohemagglutinin-induced T cell proliferation. Among them we found that hUC-MSC has the strongest effects on inhibiting T cell proliferation and is chosen to do the further study. We observed that T lymphocyte spontaneously released abundant IFN-γ. And IFN-γ secreted by T lymphocyte could induce the expression of indoleamine 2, 3-dioxygenase (IDO in hUC-MSCs. IDO was previously reported to induce T lymphocyte apoptosis and cell cycle arrest in S phase. When cocultured with hUC-MSCs, T lymphocyte expression of caspase 3 was significantly increased, while Bcl2 and CDK4 mRNA expression decreased dramatically. Addition of 1-methyl tryptophan (1-MT, an IDO inhibitor, restored T lymphocyte proliferation, reduced apoptosis, and induced resumption of the cell cycle. In addition, the changes in caspase 3, CDK4, and Bcl2 expression were reversed by 1-MT. These findings demonstrate that hUC-MSCs induce T lymphocyte apoptosis and cell cycle arrest by expressing abundant IDO and provide an explanation for some of the immunomodulatory effects of MSCs.

  16. On the Dynamical Behavior of the Cysteine Dioxygenase-l-Cysteine Complex in the Presence of Free Dioxygen and l-Cysteine.

    Science.gov (United States)

    Pietra, Francesco

    2017-11-01

    In this work, viable models of cysteine dioxygenase (CDO) and its complex with l-cysteine dianion were built for the first time, under strict adherence to the crystal structure from X-ray diffraction studies, for all atom molecular dynamics (MD). Based on the CHARMM36 FF, the active site, featuring an octahedral dummy Fe(II) model, allowed us observing water exchange, which would have escaped attention with the more popular bonded models. Free dioxygen (O 2 ) and l-cysteine, added at the active site, could be observed being expelled toward the solvating medium under Random Accelerated Molecular Dynamics (RAMD) along major and minor pathways. Correspondingly, free dioxygen (O 2 ), added to the solvating medium, could be observed to follow the same above pathways in getting to the active site under unbiased MD. For the bulky l-cysteine, 600 ns of trajectory were insufficient for protein penetration, and the molecule was stuck at the protein borders. These models pave the way to free energy studies of ligand associations, devised to better clarify how this cardinal enzyme behaves in human metabolism. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  17. Preparation, Crystallization and X-ray Diffraction Analysis to 1.5 A Resolution of Rat Cysteine Dioxygenase, a Mononuclear Iron Enzyme Responsible for Cysteine Thiol Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons,C.; Hao, Q.; Stipanuk, M.

    2005-01-01

    Cysteine dioxygenase (CDO; EC 1.13.11.20) is an {approx}23 kDa non-heme iron metalloenzyme that is responsible for the oxidation of cysteine by O2, yielding cysteinesulfinate. CDO catalyzes the first step in the conversion of cysteine to taurine, as well as the first step in the catabolism of cysteine to pyruvate plus sulfate. Recombinant rat CDO was heterologously expressed, purified and crystallized. The protein was expressed as a fusion protein bearing a polyhistidine tag to facilitate purification, a thioredoxin tag to improve solubility and a factor Xa cleavage site to permit removal of the entire N-terminus, leaving only the 200 amino acids inherent to the native protein. A multi-step purification scheme was used to achieve >95% purity of CDO. The optimal CDO crystals diffracted to 1.5 Angstroms resolution and belonged to space group P4{sub 3}2{sub 1}2 or P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 57.55, c = 123.06 Angstrom, {alpha} = {beta} = {gamma} = 90. CDO shows little homology to any other proteins; therefore, the structure of the enzyme will be determined by ab initio phasing using a selenomethionyl derivative.

  18. Kinetic and spectroscopic investigation of CoII, NiII, and N-oxalylglycine inhibition of the FeII/α-ketoglutarate dioxygenase, TauD

    International Nuclear Information System (INIS)

    Kalliri, Efthalia; Grzyska, Piotr K.; Hausinger, Robert P.

    2005-01-01

    Co II , Ni II , and N-oxalylglycine (NOG) are well-known inhibitors of Fe II /α-ketoglutarate (αKG)-dependent hydroxylases, but few studies describe their kinetics and no spectroscopic investigations have been reported. Using taurine/αKG dioxygenase (TauD) as a paradigm for this enzyme family, time-dependent inhibition assays showed that Co II and Ni II follow slow-binding inhibition kinetics. Whereas Ni II -substituted TauD was non-chromophoric, spectroscopic studies of the Co II -substituted enzyme revealed a six-coordinate site (protein alone or with αKG) that became five-coordinate upon taurine addition. The Co II spectrum was not perturbed by a series of anions or oxidants, suggesting the Co II is inaccessible and could be used to stabilize the protein. NOG competed weakly (K i ∼ 290 μM) with αKG for binding to TauD, with the increased electron density of NOG yielding electronic transitions for NOG-Fe II -TauD and taurine-NOG-Fe II -TauD at 380 nm (ε 38 90-105 M -1 cm -1 ). The spectra of the NOG-bound TauD species did not change significantly upon oxygen exposure, arguing against the formation of an oxygen-bound state mimicking an early intermediate in catalysis

  19. Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway.

    Directory of Open Access Journals (Sweden)

    Nan-Sun Kim

    Full Text Available A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1 in human dendritic cells (DCs. Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-κB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity.

  20. The potato carotenoid cleavage dioxygenase 4 catalyzes a single cleavage of β-ionone ring-containing carotenes and non-epoxidated xanthophylls

    KAUST Repository

    Bruno, Mark

    2015-04-01

    Down-regulation of the potato carotenoid cleavage dioxygenase 4 (StCCD4) transcript level led to tubers with altered morphology and sprouting activity, which also accumulated higher levels of violaxanthin and lutein leading to elevated carotenoid amounts. This phenotype indicates a role of this enzyme in tuber development, which may be exerted by a cleavage product. In this work, we investigated the enzymatic activity of StCCD4, by expressing the corresponding cDNA in carotenoid accumulating Escherichia coli strains and by performing in vitro assays with heterologously expressed enzyme. StCCD4 catalyzed the cleavage of all-. trans-β-carotene at the C9\\'-C10\\' double bond, leading to β-ionone and all-. trans-β-apo-10\\'-carotenal, both in vivo and in vitro. The enzyme also cleaved β,β-cryptoxanthin, zeaxanthin and lutein either at the C9\\'-C10\\' or the C9-C10 double bond in vitro. In contrast, we did not observe any conversion of violaxanthin and only traces of activity with 9-. cis-β-carotene, which led to 9-. cis-β-apo-10\\'-carotenal. Our data indicate that all-. trans-β-carotene is the likely substrate of StCCD4 in planta, and that this carotene may be precursor of an unknown compound involved in tuber development.

  1. Tomato carotenoid cleavage dioxygenases 1A and 1B: Relaxed double bond specificity leads to a plenitude of dialdehydes, mono-apocarotenoids and isoprenoid volatiles

    KAUST Repository

    Ilg, Andrea; Bruno, Mark; Beyer, Peter; Al-Babili, Salim

    2014-01-01

    The biosynthetic processes leading to many of the isoprenoid volatiles released by tomato fruits are still unknown, though previous reports suggested a clear correlation with the carotenoids contained within the fruit. In this study, we investigated the activity of the tomato (Solanum lycopersicum) carotenoid cleavage dioxygenase (SlCCD1B), which is highly expressed in fruits, and of its homolog SlCCD1A. Using in vitro assays performed with purified recombinant enzymes and by analyzing products formed by the two enzymes in carotene-accumulating Escherichia coli strains, we demonstrate that SlCCD1A and, to a larger extent, SlCCD1B, have a very relaxed specificity for both substrate and cleavage site, mediating the oxidative cleavage of cis- and all-. trans-carotenoids as well as of different apocarotenoids at many more double bonds than previously reported. This activity gives rise to a plenitude of volatiles, mono-apocarotenoids and dialdehyde products, including cis-pseudoionone, neral, geranial, and farnesylacetone. Our results provide a direct evidence for a carotenoid origin of these compounds and point to CCD1s as the enzymes catalyzing the formation of the vast majority of tomato isoprenoid volatiles, many of which are aroma constituents. © 2014 The Authors.

  2. The potato carotenoid cleavage dioxygenase 4 catalyzes a single cleavage of β-ionone ring-containing carotenes and non-epoxidated xanthophylls.

    Science.gov (United States)

    Bruno, Mark; Beyer, Peter; Al-Babili, Salim

    2015-04-15

    Down-regulation of the potato carotenoid cleavage dioxygenase 4 (StCCD4) transcript level led to tubers with altered morphology and sprouting activity, which also accumulated higher levels of violaxanthin and lutein leading to elevated carotenoid amounts. This phenotype indicates a role of this enzyme in tuber development, which may be exerted by a cleavage product. In this work, we investigated the enzymatic activity of StCCD4, by expressing the corresponding cDNA in carotenoid accumulating Escherichia coli strains and by performing in vitro assays with heterologously expressed enzyme. StCCD4 catalyzed the cleavage of all-trans-β-carotene at the C9'-C10' double bond, leading to β-ionone and all-trans-β-apo-10'-carotenal, both in vivo and in vitro. The enzyme also cleaved β,β-cryptoxanthin, zeaxanthin and lutein either at the C9'-C10' or the C9-C10 double bond in vitro. In contrast, we did not observe any conversion of violaxanthin and only traces of activity with 9-cis-β-carotene, which led to 9-cis-β-apo-10'-carotenal. Our data indicate that all-trans-β-carotene is the likely substrate of StCCD4 in planta, and that this carotene may be precursor of an unknown compound involved in tuber development. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Tomato carotenoid cleavage dioxygenases 1A and 1B: Relaxed double bond specificity leads to a plenitude of dialdehydes, mono-apocarotenoids and isoprenoid volatiles

    KAUST Repository

    Ilg, Andrea

    2014-06-25

    The biosynthetic processes leading to many of the isoprenoid volatiles released by tomato fruits are still unknown, though previous reports suggested a clear correlation with the carotenoids contained within the fruit. In this study, we investigated the activity of the tomato (Solanum lycopersicum) carotenoid cleavage dioxygenase (SlCCD1B), which is highly expressed in fruits, and of its homolog SlCCD1A. Using in vitro assays performed with purified recombinant enzymes and by analyzing products formed by the two enzymes in carotene-accumulating Escherichia coli strains, we demonstrate that SlCCD1A and, to a larger extent, SlCCD1B, have a very relaxed specificity for both substrate and cleavage site, mediating the oxidative cleavage of cis- and all-. trans-carotenoids as well as of different apocarotenoids at many more double bonds than previously reported. This activity gives rise to a plenitude of volatiles, mono-apocarotenoids and dialdehyde products, including cis-pseudoionone, neral, geranial, and farnesylacetone. Our results provide a direct evidence for a carotenoid origin of these compounds and point to CCD1s as the enzymes catalyzing the formation of the vast majority of tomato isoprenoid volatiles, many of which are aroma constituents. © 2014 The Authors.

  4. Tomato carotenoid cleavage dioxygenases 1A and 1B: Relaxed double bond specificity leads to a plenitude of dialdehydes, mono-apocarotenoids and isoprenoid volatiles

    Directory of Open Access Journals (Sweden)

    Andrea Ilg

    2014-01-01

    Full Text Available The biosynthetic processes leading to many of the isoprenoid volatiles released by tomato fruits are still unknown, though previous reports suggested a clear correlation with the carotenoids contained within the fruit. In this study, we investigated the activity of the tomato (Solanum lycopersicum carotenoid cleavage dioxygenase (SlCCD1B, which is highly expressed in fruits, and of its homolog SlCCD1A. Using in vitro assays performed with purified recombinant enzymes and by analyzing products formed by the two enzymes in carotene-accumulating Escherichia coli strains, we demonstrate that SlCCD1A and, to a larger extent, SlCCD1B, have a very relaxed specificity for both substrate and cleavage site, mediating the oxidative cleavage of cis- and all-trans-carotenoids as well as of different apocarotenoids at many more double bonds than previously reported. This activity gives rise to a plenitude of volatiles, mono-apocarotenoids and dialdehyde products, including cis-pseudoionone, neral, geranial, and farnesylacetone. Our results provide a direct evidence for a carotenoid origin of these compounds and point to CCD1s as the enzymes catalyzing the formation of the vast majority of tomato isoprenoid volatiles, many of which are aroma constituents.

  5. Bis(μ-biphenyl-2,2′-dicarboxylatobis[(2,2′-bipyridinecopper(II

    Directory of Open Access Journals (Sweden)

    Zhe An

    2009-04-01

    Full Text Available The title compound, [Cu2(C14H8O42(C10H8N22], was obtained by solvothermal synthesis. The CuII atom is coordinated by one chelating 2,2′-bipyridine ligand and two carboxyl groups from different biphenyl-2,2′-dicarboxylate ligands, leading to a distorted octahedral environment. Each carboxylate group makes one short Cu—O bond [1.9608 (14 and 1.9701 (14 Å] and one longer Cu—O contact [2.4338 (17 and 2.5541 (17 Å] to each CuII atom. The biphenyl-2,2′-dicarboxylate ligands bridge between CuII atoms, forming a dinuclear complex around a crystallographic inversion centre.

  6. Transcriptome profiling and digital gene expression analysis of genes associated with salinity resistance in peanut

    Directory of Open Access Journals (Sweden)

    Jiongming Sui

    2018-03-01

    Full Text Available Background: Soil salinity can significantly reduce crop production, but the molecular mechanism of salinity tolerance in peanut is poorly understood. A mutant (S1 with higher salinity resistance than its mutagenic parent HY22 (S3 was obtained. Transcriptome sequencing and digital gene expression (DGE analysis were performed with leaves of S1 and S3 before and after plants were irrigated with 250 mM NaCl. Results: A total of 107,725 comprehensive transcripts were assembled into 67,738 unigenes using TIGR Gene Indices clustering tools (TGICL. All unigenes were searched against the euKaryotic Ortholog Groups (KOG, gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG databases, and these unigenes were assigned to 26 functional KOG categories, 56 GO terms, 32 KEGG groups, respectively. In total 112 differentially expressed genes (DEGs between S1 and S3 after salinity stress were screened, among them, 86 were responsive to salinity stress in S1 and/or S3. These 86 DEGs included genes that encoded the following kinds of proteins that are known to be involved in resistance to salinity stress: late embryogenesis abundant proteins (LEAs, major intrinsic proteins (MIPs or aquaporins, metallothioneins (MTs, lipid transfer protein (LTP, calcineurin B-like protein-interacting protein kinases (CIPKs, 9-cis-epoxycarotenoid dioxygenase (NCED and oleosins, etc. Of these 86 DEGs, 18 could not be matched with known proteins. Conclusion: The results from this study will be useful for further research on the mechanism of salinity resistance and will provide a useful gene resource for the variety breeding of salinity resistance in peanut. Keywords: Digital gene expression, Gene, Mutant, NaCl, Peanut (Arachis hypogaea L., RNA-seq, Salinity stress, Salinity tolerance, Soil salinity, Transcripts, Unigenes

  7. C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents.

    Science.gov (United States)

    Ding, Yuyang; Mao, Liufeng; Xu, Dengfeng; Xie, Hui; Yang, Ling; Xu, Hongjiang; Geng, Wenjun; Gao, Yong; Xia, Chunguang; Zhang, Xiquan; Meng, Qingyi; Wu, Donghai; Zhao, Junling; Hu, Wenhui

    2015-07-15

    A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Alteration of General Behavior of Male Medaka,oryzias latipes,Exposed to Tributyltin and /or Polychlorinated Biphenyls

    OpenAIRE

    Nakayama, Kei; Oshima, Yuji; Hiramatsu, Kazuaki; Honjo, Tsuneo

    2004-01-01

    We examined the general behavior of male Japanese medaka, Oryzias latipes, after exposed to tributyltin (TBT), polychlorinated biphenyls (PCBs), or a mixture of these chamicals at a concentration of 1μg/g body weight daily for 3 weeks. We analyzed swimming velocity as an indicator of acute toxicity and counted the frequencies of straight swimming and swimming in circles. We also calclated the entropy of the positions of the fish within the experimental chamber. Neither TBT nor PCBs nor their ...

  9. Congener-specific polychlorinated biphenyl patterns in eggs of aquatic birds from the lower Laguna Madre, Texas

    Science.gov (United States)

    Mora, Miguel A.

    1996-01-01

    Eggs from four aquatic bird species nesting in the Lower Laguna Madre, Texas, were collected to determine differences and similarities in the accumulation of congener-specific polychlorinated biphenyls (PCBs) and to evaluate PCB impacts on reproduction. Because of the different toxicities of PCB congeners, it is important to know which congeners contribute most to total PCBs. The predominant PCB congeners were 153, 138, 180, 110, 118, 187, and 92. Collectively, congeners 153, 138, and 180 accounted for 26 to 42% of total PCBs. Congener 153 was the most abundant in Caspian terns (Sterna caspia) and great blue herons (Ardea herodias) and congener 138 was the most abundant in snowy egrets (Egretta thula) and tricolored herons (Egretta tricolor). Principal component analysis indicated a predominance of higher chlorinated biphenyls in Caspian terns and great blue herons and lower chlorinated biphenyls in tricolored herons. Snowy egrets had a predominance of pentachlorobiphenyls. These results suggest that there are differences in PCB congener patterns in closely related species and that these differences are more likely associated with the species' diet rather than metabolism. Total PCBs were significantly greater (p birds from the Lower Laguna Madre were below concentrations known to affect bird reproduction.

  10. Magnetoelectrochemistry of 4,4'-bis(dimethylamino)biphenyl and 4,4'-dinitrobiphenyl azacrown macrocyclic lactams

    Energy Technology Data Exchange (ETDEWEB)

    Domenech, Antonio [Departament de Quimica Analitica, Universitat de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia (Spain); Costero, Ana Maria; Banuls, Maria Jose; Aurell, Maria Jose [Departament de Quimica Organica, Universitat de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia (Spain)

    2005-07-25

    The voltammetric behaviour at carbon fibre microelectrodes under the application of static magnetic fields of two series of macrolactams containing in their structure 4,4'-bis(dimethylamino)biphenyl or 4,4'-dinitrobiphenyl groups in MeCN solution is described. The response of 4,4'-dinitrobiphenyl receptors is dominated by two successive one-electron reduction processes at -0.9 and -1.6 V versus AgCl/Ag. 4,4'-bis(dimethylamino)biphenyl-containing receptors display two one-electron oxidations above +0.8 and +1.0 V. In both cases, a dihedral/planar interconversion precedes the second electron transfer step. Upon application of moderate (0.05-0.2 T) static magnetic fields to the electrochemical cell, the rate of such dihedral/planar interconversion is lowered for both the reduction of 4,4'-dinitrobiphenyl receptors and the oxidation of 4,4'-bis(dimethylamino)biphenyl lactams. The electrochemical response of N-methylated receptors, for which different cisoid-cisoid, cisoid-transoid, and transoid-transoid forms exist, exhibits a significant peak splitting that can be associated to the presence of such conformational isomers. Application of magnetic fields produces a relative enhancement of some peaks that can be interpreted in terms of differential magnetoconvection involving such conformational isomers. (author)

  11. Photo/electroluminescence properties of an europium (III) complex doped in 4,4'-N,N'-dicarbazole-biphenyl matrix

    International Nuclear Information System (INIS)

    Zhou Yonghui; Zhou Liang; Wu, Jing; Li, Hong-Yan; Zheng Youxuan; You Xiaozeng; Zhang Hongjie

    2010-01-01

    The photoluminescence properties of one europium complex Eu(TFNB) 3 Phen (TFNB = 4,4,4-trifluoro-1-(naphthyl)-1,3-butanedione, Phen = 1,10-phenanthroline) doped in a hole-transporting material CBP (4,4'-N,N'-dicarbazole-biphenyl) films were studied. A series of organic light-emitting devices (OLEDs) using Eu(TFNB) 3 Phen as the emitter were fabricated with a multilayer structure of indium tin oxide, 250 Ω/square)/TPD (N,N'-diphenyl-N,N'-bis(3-methyllphenyl)-(1,1'-biphenyl)-4,4'-diamine, 50 nm)/Eu(TFNB) 3 phen (x): CBP (4,4'-N,N'-dicarbazole-biphenyl, 45 nm)/BCP (2,9-dimethyl-4,7-diphenyl-l,10 phenanthroline, 20 nm)/AlQ (tris(8-hydroxy-quinoline) aluminium, 30 nm)/LiF (1 nm)/Al (100 nm), where x is the weight percentage of Eu(TFNB) 3 phen doped in the CBP matrix (1-6%). A red emission at 612 nm with a half bandwidth of 3 nm, characteristic of Eu(III) ion, was observed with all devices. The device with a 3% dopant concentration shows the maximum luminance up to 1169 cd/m 2 (18 V) and the device with a 5% dopant concentration exhibits a current efficiency of 4.46 cd/A and power efficiency of 2.03 lm/W. The mechanism of the electroluminescence was also discussed.

  12. Conductivity and applications of Li-biphenyl-1,2-dimethoxyethane solution for lithium ion batteries

    Institute of Scientific and Technical Information of China (English)

    Geng Chu; Bo-Nan Liu; Fei Luo; Wen-Jun Li; Hao Lu; Li-Quan Chen; Hong Li

    2017-01-01

    The total conductivity of Li-biphenyl-l,2-dimethoxyethane solution (LixBp(DME)9.65,Bp =biphenyl,DME =1,2-dimethoxyethane,x =0.25,0.50,1.00,1.50,2.00) is measured by impedance spectroscopy at a temperature range from 0 ℃C to 40 ℃C.The Li1.50Bp(DME)9.65 has the highest total conductivity 10.7 mS/cm.The conductivity obeys Arrhenius law with the activation energy (Ea(x=0.50) =0.014 eV,Ea(x=1.00) =0.046 eV).The ionic conductivity and electronic conductivity of LixBp(DME)9.65 solutions are investigated at 20 ℃C using the isothermal transient ionic current (ITIC) technique with an ion-blocking stainless steal electrode.The ionic conductivity and electronic conductivity of Li1.00Bp(DME)9.65 are measured as 4.5 mS/cm and 6.6 mS/cm,respectively.The Li1.00Bp(DME)9.65 solution is tested as an anode material of half liquid lithium ion battery due to the coexistence of electronic conductivity and ionic conductivity.The lithium iron phosphate (LFP) and Li1.5Al0.5Ti1.5(PO4)3 (LATP) are chosen to be the counter electrode and electrolyte,respectively.The assembled cell is cycled in the voltage range of 2.2 V-3.75 V at a current density of 50 mA/g.The potential of Lit.00Bp(DME)9.65 solution is about 0.3 V vs.Li+/Li,which indicates the solution has a strong reducibility.The Li1.00Bp(DME)9.65 solution is also used to prelithiate the anode material with low first efficiency,such as hard carbon,soft carbon and silicon.

  13. Identification of a novel dimethoxylated polybrominated biphenyl bioaccumulating in marine mammals

    Energy Technology Data Exchange (ETDEWEB)

    Marsh, G.; Athanasiadou, M.; Bergman, Aa.; Athanassiadis, I. [Department of Environmental Chemistry, Stockholm (Sweden); Endo, Tetsuya [Health Sciences Univ. of Hokkaido (Japan). Fac. of Pharmaceutical Sciences; Haraguchi, Koichi [Daiichi College of Pharmaceutical Sciences, Fukuoka (Japan)

    2004-09-15

    The screening of persistent halogenated organic pollutants has in recent years ended up with findings of numerous compounds being natural products. These compounds have preferably been reported from the marine environment and comprise, several hydroxylated and methoxylated polybrominated diphenyl ethers (OH-PBDEs and MeO-PBDEs) including monochlorinated ditto, a dimethoxylated polybrominated diphenyl ether i.e. 2',6-dimethoxy-2,3',4,5'-tetrabromodiphenyl ether, four halogenated dimethylated bipyrroles (HDBPs) with a 2,2'-bipyrrole backbone, a heptachlorinated 1,2'-bipyrrole i.e. heptachloro-1'-methyl-1,2'-bipyrrole (Q1)6 and a halogenated monoterpene holding two bromine and three chlorine atoms. We have taken interest in an organobrominated compound with an unknown structure but with a molecule ion of m/z = 526 and a four bromine isotope pattern according to mass spectrometry (MS), detected in marine mammal samples of which the majority were collected from Japanese coastal waters. This compound has recently been reported from several marine mammals collected on the Southern hemisphere, but neither the chemical structure nor the type of substance group were established. We here report the structure of this organobrominated compound, a dimethoxylated polybrominated biphenyl, which likely is of natural origin. The identification was done by the comparison of relative retention time (RRT) on two GC columns with different polarities and by comparing mass spectra from three different ionization techniques i.e. PICI, ECNI and EI, of the unknown compound from the samples with an authentic reference compound. Levels of the novel dimethoxylated polybrominated biphenyl are reported as well as the levels (for comparison) of some other known polybrominated compounds, both brominated flame retardants (BFRs) and natural products i.e. BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, 1,2,5,6,9,10- hexabromocyclododecane (HBCDD), 6-MeO-BDE-47, 2

  14. Isolation and characterisation of polychlorinated biphenyl (PCB degrading fungi from a historically contaminated soil

    Directory of Open Access Journals (Sweden)

    Di Toro Sara

    2009-01-01

    Full Text Available Abstract Background Polychlorinated biphenyls (PCBs are widespread toxic pollutants. Bioremediation might be an effective, cost competitive and environment-friendly solution for remediating environmental matrices contaminated by PCBs but it is still unsatisfactory, mostly for the limited biodegradation potential of bacteria involved in the processes. Very little is known about mitosporic fungi potential in PCB bioremediation and their occurrence in actual site historically contaminated soils. In the present study, we characterised the native mycoflora of an aged dump site soil contaminated by about 0.9 g kg-1 of Aroclor 1260 PCBs and its changing after aerobic biotreatment with a commercial complex source of bacteria and fungi. Fungi isolated from the soil resulting from 120 days of treatment were screened for their ability to adsorb or metabolise 3 target PCBs. Results The original contaminated soil contained low loads of few fungal species mostly belonging to the Scedosporium, Penicillium and Aspergillus genera. The fungal load and biodiversity generally decreased throughout the aerobic treatment. None of the 21 strains isolated from the treated soil were able to grow on biphenyl (200 mg L-1 or a mixture of 2-chlorobiphenyl, 4,4'-dichlorobiphenyl and 2,2',5,5'-tetrachlorobiphenyl (20 mg L-1 each as sole carbon sources. However, 16 of them grew in a mineral medium containing the same PCBs mixture and glucose (10 g L-1. Five of the 6 isolates, which displayed the faster and more extensive growth under the latter conditions, were found to degrade the 3 PCBs apparently without the involvement of ligninolytic enzymes; they were identified as Penicillium chrysogenum, Scedosporium apiospermum, Penicillium digitatum and Fusarium solani. They are the first PCB degrading strains of such species reported so far in the literature. Conclusion The native mycoflora of the actual site aged heavily contaminated soil was mainly constituted by genera often

  15. Environmental Application of Reporter-Genes Based Biosensors for Chemical Contamination Screening

    Directory of Open Access Journals (Sweden)

    Matejczyk Marzena

    2014-12-01

    Full Text Available The paper presents results of research concerning possibilities of applications of reporter-genes based microorganisms, including the selective presentation of defects and advantages of different new scientific achievements of methodical solutions in genetic system constructions of biosensing elements for environmental research. The most robust and popular genetic fusion and new trends in reporter genes technology – such as LacZ (β-galactosidase, xylE (catechol 2,3-dioxygenase, gfp (green fluorescent proteins and its mutated forms, lux (prokaryotic luciferase, luc (eukaryotic luciferase, phoA (alkaline phosphatase, gusA and gurA (β-glucuronidase, antibiotics and heavy metals resistance are described. Reporter-genes based biosensors with use of genetically modified bacteria and yeast successfully work for genotoxicity, bioavailability and oxidative stress assessment for detection and monitoring of toxic compounds in drinking water and different environmental samples, surface water, soil, sediments.

  16. Limnobacter spp. as newly detected phenol-degraders among Baltic Sea surface water bacteria characterised by comparative analysis of catabolic genes.

    Science.gov (United States)

    Vedler, Eve; Heinaru, Eeva; Jutkina, Jekaterina; Viggor, Signe; Koressaar, Triinu; Remm, Maido; Heinaru, Ain

    2013-12-01

    A set of phenol-degrading strains of a collection of bacteria isolated from Baltic Sea surface water was screened for the presence of two key catabolic genes coding for phenol hydroxylases and catechol 2,3-dioxygenases. The multicomponent phenol hydroxylase (LmPH) gene was detected in 70 out of 92 strains studied, and 41 strains among these LmPH(+) phenol-degraders were found to exhibit catechol 2,3-dioxygenase (C23O) activity. Comparative phylogenetic analyses of LmPH and C23O sequences from 56 representative strains were performed. The studied strains were mostly affiliated to the genera Pseudomonas and Acinetobacter. However, the study also widened the range of phenol-degraders by including the genus Limnobacter. Furthermore, using a next generation sequencing approach, the LmPH genes of Limnobacter strains were found to be the most prevalent ones in the microbial community of the Baltic Sea surface water. Four different Limnobacter strains having almost identical 16S rRNA gene sequences (99%) and similar physiological properties formed separate phylogenetic clusters of LmPH and C23O genes in the respective phylogenetic trees. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Exposure to polychlorinated biphenyls and the thyroid gland – examining and discussing possible longitudinal health effects in humans

    Energy Technology Data Exchange (ETDEWEB)

    Gaum, Petra M., E-mail: pgaum@ukaachen.de [Institute for Occupational and Social Medicine, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen (Germany); Lang, Jessica; Esser, André; Schettgen, Thomas [Institute for Occupational and Social Medicine, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen (Germany); Neulen, Joseph [Clinic for Gynaecological Endocrinology and Reproductive Medicine, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen (Germany); Kraus, Thomas; Gube, Monika [Institute for Occupational and Social Medicine, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen (Germany)

    2016-07-15

    Background: Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. Objectives: The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. Methods: A total of 122 individuals (M{sub age}=44.7) were examined over a period of four years (t{sup 1} until t{sup 4}). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. Results: There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. Conclusion: This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation. - Highlights: • This is a longitudinal study which includes data from four cross sections. • Higher-chlorinated biphenyls are negatively correlated with fT3. • There are interactions of time and higher-chlorinated biphenyls to TSHRab and fT4.

  18. Source determination of highly chlorinated biphenyl isomers in pine needles - Comparison to several PCB preparations

    International Nuclear Information System (INIS)

    Wyrzykowska, Barbara; Bochentin, Ilona; Hanari, Nobuyasu; Orlikowska, Anna; Falandysz, Jerzy; Yuichi, Horii; Yamashita, Nobuyoshi

    2006-01-01

    The isomer specific composition of 13 technical PCB formulations of different origin and of pine needles was analyzed using GC/MS and HRGC/HRMS. Nonachlorinated biphenyls were identified in 11 among 13 formulations analyzed, with the highest abundance found for highly chlorinated ones (Aroclors 1268 and 1260, Chlorofen, Sovol, Kanechlors 600 and 500, Delor 106, Clophen A60). Decachlorobiphenyl was identified only in Aroclor 1268, Clophen A60, Aroclor 1260 and Chlorofen, comprising, respectively, 8.9, 2.8, 1.3 and 0.82% of the total bulk of nona- and decaCBs detected. Nona- and decaCB were detected in pine needles in Poland with the highest concentrations found at the sites neighboring to a former production sites of the Polish PCB formulations, while in pine needles collected around the Tokyo Bay nona- and decacCB were detected only in four of 10 sites and the concentrations corresponded to those found at the rural areas of Poland. - Pine needles were suitable as passive samplers for PCBs in air

  19. Polychlorinated biphenyl concentrations in pooled serum from people in different age groups from five Chinese cities.

    Science.gov (United States)

    Wang, Qinghua; Yuan, Haodong; Jin, Jun; Li, Peng; Ma, Yulong; Wang, Ying

    2018-05-01

    Polychlorinated biphenyl (PCB) concentrations in human serum samples pooled by donor age and sex (≥60, 50-59, 40-49, 30-39, and 20-29 years old) were determined. The pooled samples were supplied by hospitals in five Chinese cities, which were Yitong (Jilin Province), Weifang (Shandong Province), Ganzi (Sichuan Province), Huaihua (Hunan Province), and Lingshui (Hainan Province). The total PCB concentrations were relatively low compared with concentrations that have been found in other parts of the world. Pentachlorobiphenyls were the dominant PCBs. The total PCB concentrations and the concentrations of most of the pentachlorobiphenyl congeners were slightly higher in the samples from younger donors than in the samples from older donors. The results indicated there is a new source of PCBs in China. Heptachlorobiphenyls in Lingshui may have been transported from Vietnam. Statistical analysis showed that young and old people had been exposed to different sources of PCBs. PCB 126 contributed more than the other dioxin-like PCBs to the total toxic equivalents when the samples were examined as a whole or by city, and the total toxic equivalents were higher in younger people than in older people for the whole sample set and for the Yitong samples. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Decomposition of polychlorinated biphenyls in soil with a dispersion mixture of metallic calcium and calcium oxide.

    Science.gov (United States)

    Mitoma, Yoshiharu; Mallampati, Srinivasa Reddy; Miyata, Hideaki; Kakeda, Mitsunori

    2013-02-01

    This study describes the decomposition of polychlorinated biphenyls (PCBs) in soil with dispersion mixtures of metallic calcium (Ca) and calcium oxide (CaO) at different temperatures. In these experiments, naturally moisturized and contaminated soil (1.0 g [31 ppm PCBs]), CaO (dried 2.0 wt%), and metallic Ca (0.01 g [0.25 mmol]) were introduced into a stainless steel pressure reactor under 0.1 MPa N(2) gas. The mixtures were stirred magnetically and heated at 260, 280, and 300 °C, respectively. Soil treatment with metallic Ca and CaO under various temperature conditions is extremely effective for degrading existing PCBs. Decomposition resulted from dechlorination (DC). Initial moisture in soil acted as a hydrogen source during stirring. Soil moisture can be beneficial for hydrodechlorination in the presence of metallic Ca and CaO. Furthermore, metallic Ca and CaO can greatly increase the number of collisions and mutual refinement. Treatment at 260, 280, and 300 °C combined with metallic Ca and CaO is effective for the decomposition (approximately 95 % DC) of PCBs in soil under natural moisture conditions.

  1. Seasonal air-water exchange fluxes of polychlorinated biphenyls in the Hudson River Estuary

    International Nuclear Information System (INIS)

    Yan Shu; Rodenburg, Lisa A.; Dachs, Jordi; Eisenreich, Steven J.

    2008-01-01

    Polychlorinated biphenyls (PCBs) were measured in the air and water over the Hudson River Estuary during six intensive field campaigns from December 1999 to April 2001. Over-water gas-phase ΣPCB concentrations averaged 1100 pg/m 3 and varied with temperature. Dissolved-phase ΣPCB concentrations averaged 1100 pg/L and displayed no seasonal trend. Uncertainty analysis of the results suggests that PCBs with 5 or fewer chlorines exhibited net volatilization. The direction of net air/water exchange could not be determined for PCBs with 6 or more chlorines. Instantaneous net fluxes of ΣPCBs ranged from +0.2 to +630 ng m -2 d -1 . Annual fluxes of ΣPCBs were predicted from modeled gas-phase concentrations, measured dissolved-phase concentrations, daily surface water temperatures and wind speeds. The net volatilization flux was +62 μg m -2 yr -1 , corresponding to an annual loss of +28 kg/yr of ΣPCBs from the Hudson River Estuary for the year of 2000. - Investigation of the air-water exchange of PCBs in the Hudson River Estuary suggests that PCBs with 5 or fewer chlorines undergo net volatilization

  2. Combined effect of microwave and activated carbon on the remediation of polychlorinated biphenyl-contaminated soil.

    Science.gov (United States)

    Liu, Xitao; Yu, Gang

    2006-04-01

    The application of microwave and activated carbon for the treatment of polychlorinated biphenyl (PCB) contaminated soil was explored in this study with a model compound of 2,4,5-trichlorobiphenyl (PCB29). PCB-contaminated soil was treated in a quartz reactor by microwave irradiation at 2450MHz with the addition of granular activated carbon (GAC). In this procedure, GAC acted as microwave absorbent for reaching high temperature and reductant for dechlorination. A sheltered type-K thermocouple was applied to record the temperature rising courses. It was shown that the addition of GAC could effectively promote the temperature rising courses. The determination of PCB residues in soil by gas chromatography (GC) revealed that rates of PCB removal were highly dependent on microwave power, soil moisture content, and the amount of GAC added. GC with mass spectrum (MS) detector and ion chromatography were employed for the analysis of degradation intermediates and chlorine ions, respectively. It was suggested that microwave irradiation with the assistance of activated carbon might be a potential technology for the remediation of PCB-contaminated soil.

  3. Remediation of soils contaminated with polychlorinated biphenyls by microwave-irradiated manganese dioxide

    International Nuclear Information System (INIS)

    Huang Guanyi; Zhao Ling; Dong Yuanhua; Zhang Qin

    2011-01-01

    The removal of polychlorinated biphenyls (PCBs) using microwave-irradiated manganese dioxide (MnO 2 ) in PCB-contaminated soils under different conditions is investigated. The removal of PCB77 in two actual soil samples exhibits strong pH-dependent behavior, and the removal efficiency is higher in acidic soil (Ali-Perudic Ferrosols) than that in neutral soil (Udic Argosols). The removal kinetics of PCB77 using microwave-irradiated MnO 2 under different experimental conditions fits a pseudo-first-order kinetic model well. Both the removal efficiency and the kinetic constant (k) values of PCB77 in Ali-Perudic Ferrosols considerably increase, although in a nonlinear fashion, as the initial amount of MnO 2 is increased, as the treated soil mass is increased, and as the microwave power is increased. The reactivity of three PCBs (PCB28, PCB77, and PCB118) did not present as a function of the degree of chlorination in the reaction with microwave-irradiated MnO 2 . The pronounced removal of three PCBs in contaminated soil (all above 95%) indicates that MnO 2 in combination with microwave irradiation is promising for technological applications that seek to remediate sites critically polluted with PCBs.

  4. Method and means for filtering polychlorinated biphenyls from a gas stream

    International Nuclear Information System (INIS)

    Sowinski, R.F.

    1992-01-01

    This patent describes a method of filtering, adjacent to an end user-customer's residence or business in which at least a single gas appliance is located, a natural gas stream in which polychlorinated biphenyls (PCB's) and degraded PCB products have been concentrated at sufficient levels to be a health threat in a natural gas gathering and distributing network. It comprises: introducing the natural gas stream to a filter selected from a group that includes impingement, absorbing and adsorbing media whereby PCB's and degraded PCB products concentrated in the gas stream at sufficient levels to be a health threat by a periodic loading of the natural gas within the gathering and distributing network, are filtered from the gas stream and captured irrespective of mode of transport, passing the filtered natural gas stream to the customer's gas appliance wherein safe use of the energy associated with the stream occurs; periodically and safely removing the filter, inserting a new filter in place of the removed filter

  5. The uridine diphosphate glucuronosyltransferases: quantitative structure-activity relationships for hydroxyl polychlorinated biphenyl substrates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Degao [Dalian University of Technology, Department of Environmental Science and Technology, Dalian (China)

    2005-10-01

    Quantitative structure-activity relationships (QSARs), which relate the glucuronidation of hydroxyl polychlorinated biphenyls (OH-PCBs) - catalyzed by the uridine diphosphate glucuronosyltransferases (UGTs) - to their physicochemical properties and molecular structural parameters, can be used to predict the rate constants and interpret the mechanism of glucuronidation. In this study, QSARs have been developed that use 23 semi-empirical calculated quantum chemical descriptors to predict the logarithms of the constants 1/K{sub m} and V{sub max}, related to enzyme kinetics. A partial least squares regression method was used to select the optimal set of descriptors to minimize the multicollinearity between the descriptors, as well as to maximize the cross-validated coefficient (Q{sup 2} {sub cum}) values. The key descriptors affecting log(1/K{sub m}) were E{sub lumo}- E{sub homo} (the energy gap between the lowest unoccupied molecular orbital and the highest occupied molecular orbital) and q{sub C}{sup -} (the largest negative net atomic charge on a carbon atom), while the key descriptors affecting log V{sub max} were the polarizability {alpha}, the Connolly solvent-excluded volume (CSEV), and logP (the logarithm of the partition coefficient for octanol/water). From the results obtained it can be concluded that hydrophobic and electronic aspects of OH-PCBs are important in the glucuronidation of OH-PCBs. (orig.)

  6. Persistent or not persistent? Polychlorinated biphenyls are readily depurated by grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    Christensen, Jennie R; Letcher, Robert J; Ross, Peter S

    2009-10-01

    Major pharmacokinetic processes influencing polychlorinated biphenyl (PCB) accumulation in mammals include uptake, biotransformation, respiration, and excretion. We characterized some of the factors underlying PCB accumulation/loss by evaluating PCB concentrations and patterns in pre- and posthibernation grizzly bears (Ursus arctos horribilis) and their prey. The PCB congeners with vicinal meta- and para-chlorine unsubstituted hydrogen positions consistently showed loss both before and during hibernation, supporting the idea of a dominant role for biotransformation. Retention of all other studied congeners relative to that of PCB 194 varied widely (from bears do not eat or excrete. We estimate that grizzly bears retain less than 10% of total PCBs taken up from their diet. Our results suggest that for grizzly bears, depuration of PCBs via biotransformation is important (explaining approximately 40% of loss), but that nonbiotransformation processes, such as excretion, may be more important (explaining approximately 60% of loss). These findings, together with the approximately 91% loss of the persistent PCB 153 congener relative to PCB 194 in grizzly bears, raise important questions about how one defines persistence of PCBs in wildlife and may have bearing on the interpretation of food-web biomagnification studies.

  7. Determination of non-ortho polychlorinated biphenyls in environmental Standard Reference Materials.

    Science.gov (United States)

    Brubaker, W W; Schantz, M M; Wise, S A

    2000-07-01

    The concentrations of three non-ortho ("coplanar") polychlorinated biphenyls, 3,3',4,4'-tetrachlorobiphenyl (IUPAC PCB 77), 3,3',4,4',5-pentachlorobiphenyl (IUPAC PCB 126), and 3,3',4,4',5,5'-hexachlorobiphenyl (IUPAC PCB 169), were determined in five NIST Standard Reference Materials (SRMs) of environmental and biological interest. The measured levels were approximately between (0.2 to 1.3) ng/g in SRM 1588a (Organics in Cod Liver Oil), (0.3 to 9) ng/g in SRM 1944 (New York/New Jersey Waterway Sediment), (0.2 to 0.4) ng/g in SRM 1945 (Organics in Whale Blubber), (1 to 18) ng/g in SRM 2974 (Organics in Freeze-dried Mussel Tissue [Mytilus edulis]), and (0.1 to 0.4) ng/g in candidate SRM 1946 (Lake Superior Fish Tissue). PCB 169 was present at < 0.1 ng/g in SRMs 1944 and 2974.

  8. Forecasting long-range atmospheric transport episodes of polychlorinated biphenyls using FLEXPART

    Science.gov (United States)

    Halse, Anne Karine; Eckhardt, Sabine; Schlabach, Martin; Stohl, Andreas; Breivik, Knut

    2013-06-01

    The analysis of concentrations of persistent organic pollutants (POPs) in ambient air is costly and can only be done for a limited number of samples. It is thus beneficial to maximize the information content of the samples analyzed via a targeted observation strategy. Using polychlorinated biphenyls (PCBs) as an example, a forecasting system to predict and evaluate long-range atmospheric transport (LRAT) episodes of POPs at a remote site in southern Norway has been developed. The system uses the Lagrangian particle transport model FLEXPART, and can be used for triggering extra ("targeted") sampling when LRAT episodes are predicted to occur. The system was evaluated by comparing targeted samples collected over 12-25 h during individual LRAT episodes with monitoring samples regularly collected over one day per week throughout a year. Measured concentrations in all targeted samples were above the 75th percentile of the concentrations obtained from the regular monitoring program and included the highest measured values of all samples. This clearly demonstrates the success of the targeted sampling strategy.

  9. Assessment of atmospheric distribution of polychlorinated biphenyls and polycyclic aromatic hydrocarbons using polyparameter model

    Directory of Open Access Journals (Sweden)

    Turk-Sekulić Maja M.

    2011-01-01

    Full Text Available Results of partial or total destruction of industrial plants, military targets, infrastructure, uncontrolled fires and explosions during the conflict period from 1991 to 1999, at the area of Western Balkans, were large amounts of hazardous organic matter that have been generated and emitted in the environment. In order to assess gas/particle partition of seven EPA polychlorinated biphenyls and sixteen EPA polycyclic aromatic hydrocarbons, twenty air samples have been collected at six urban, industrial and highly contaminated localities in Vojvodina. Hi-Vol methodology has been used for collecting ambiental air samples, that simultaneously collects gaseous and particulate phase with polyurethane foam filters (PUF and glass fiber filters (GFF. PUF and GFF filters have been analyzed, and concentration levels of gaseous PCBs and PAHs molecules in gaseous and particulate phase were obtained, converted and expressed through fraction of individual compounds sorbed onto particulate phase of the sample, in total detected quantity. Experimentally gained gas/particle partitioning values of PCBs and PAHs molecules have been compared with PP-LFER model estimated values. Significant deviation has been noticed during comparative analysis of estimated polyparameter model values for complete set of seven PCBs congeners. Much better agreement of experimental and estimated values is for polycyclic aromatic hydrocarbons, especially for molecules with four rings. These results are in a good correlation with literature data where polyparameter model has been used for predicting gas/particle partition of studied group of organic molecules.

  10. Characteristics of trophic transfer of polychlorinated biphenyls in marine organisms in Incheon North Harbor, Korea.

    Science.gov (United States)

    Kim, Seung Kyu; Lee, Dong Soo; Oh, Jae Ryong

    2002-04-01

    The trophic transfer of polychlorinated biphenyls (PCBs) was characterized for zooplankton (primarily Paracalanus spp. and Acartia spp.), pacific oyster (Crassostrea gigas), shore crab (Hemigrapsus penicillatus), and goby (Acanthogobius hasta) in the aquatic system of Incheon North Harbor, Korea. The congener pattern in the species was clearly divided by the main PCB uptake route. Compared with zooplankton and oyster, the fraction of heavier homologues increased in crab and goby that take PCBs from food. Linear relationships were observed between log (fugacity in lipid/fugacity in seawater) and log Kow for all the species. For zooplankton and oyster, such an observation should not be regarded as a true absence of superhydrophobicity, because establishment of equilibrium with seawater was not evident. For crab and goby, the absence of superhydrophobicity was evidenced by the trophic transfer factor that continuously increased with Kow up to 10(7.8). These results suggest that superhydrophobicity might be species specific. The trophic transfer factors and the fugacity levels in the lipid phase indicated that bioaccumulation in crab and goby advanced beyond the level in equilibrium with seawater in the harbor basin.

  11. Polychlorinated biphenyls in tree bark near a former manufacturing plant in Anniston, Alabama.

    Science.gov (United States)

    Hermanson, Mark H; Johnson, Glenn W

    2007-05-01

    Tree bark samples were collected to identify the relative amounts and congener profiles of atmospheric polychlorinated biphenyls dissolved into bark lipids from the gas phase in Anniston, Alabama, USA, where PCBs were manufactured from the 1920s until 1971. The area is heavily contaminated with PCBs: At least 4550 metric tons (mt) of PCB and 14000 mt of PCB distillation residue, known as Montar, remain buried in two landfills near the plant site. A minimum of 20.5 mt of PCBs were emitted to the atmosphere by the plant between 1953 and 1971 based on emissions figures for 1970. Bark results show that total PCB concentrations range over more than three orders of magnitude from 171927 ng/g lipid near the plant/landfill area, dropping exponentially to 35 ng/g lipid at a distance of about 7 km. The exponential trend is highly correlated (r=-0.77) and significant (ptree started growing after 1971 showing that atmospheric PCB concentrations remained high after PCB production ended. All PCB congener profiles show persistent congeners 31+28, 52, 66, 153, 138, and 180. Congener profiles from trees growing near the plant/landfill all have somewhat similar profiles but those growing during PCB production show high molecular mass compounds not usually found in the atmosphere and not found in younger trees, even in the most concentrated sample. We believe that high-temperature Montar disposal released high molecular mass PCBs into the gas phase which were dissolved into older tree bark lipids.

  12. An improved inventory of polychlorinated biphenyls in China: A case study on PCB-153

    Science.gov (United States)

    Xu, Yue; Tian, Chongguo; Wang, Xiaoping; Ma, Jianmin; Tang, Jianhui; Chen, Yingjun; Li, Jun; Zhang, Gan

    2018-06-01

    Emission inventory of pollutants is essential for the environmental fate study and management of the pollutant. To construct a reasonable PCB (polychlorinated biphenyls) inventory in China, this study estimates PCB usage and emission using power generating capacity, installed capacity of power plants and transformer substations, population density and GDP as surrogates. Inventory of representative PCB (PCB-153) with a resolution of 1/4° latitude × 1/4° longitude in China from 1952 to 2005 was generated and assessed as an example. Totally, about 20.3 kt PCBs were applied in China, of which 179 t were PCB-153. By the end of 2005, most of them (56.4%) were emitted into the soil, 2.7% entered the air, and about 20.8% was sealed in storage site or still in service. Historical emissions exhibited increasing trends after 1968, 1984 and 1994, which were mainly associated with usage or disposal processes. Although primary emission has been declined since 2005, the influence of secondary emission from soils, unintentionally produced PCBs (UP-PCB), and reemission from storage sites could be a long-lasting issue in the future. This new emission inventory improves previous PCB emission inventory significantly, which underestimated PCB emission in China considerably.

  13. Biofilms at work: Bio-, phyto- and rhizoremediation approaches for soils contaminated with polychlorinated biphenyls

    Directory of Open Access Journals (Sweden)

    Merily Horwat

    2015-09-01

    Full Text Available Organohalide contaminants such as polychlorinated biphenyls (PCBs have been released into the environment for decades due to anthropogenic activities, but are also naturally produced in small amounts through volcanic eruptions and geochemical processes. Although toxic to humans and other organisms, the natural production of these compounds has resulted in the evolution of naturally occurring organohalide-respiring bacteria that possess the enzymes necessary to degrade PCB compounds to non-toxic products. The efficiency of PCB degradation can be improved by facilitating the formation of organohalide-respiring biofilms. During biofilm colonization on a surface or interface, bacteria are encased in an extracellular polymeric substance (EPS or “slime,” which allows them to share nutrients and remain protected from environmental stresses. Effective bioremediation of PCBs involves facilitation of biofilm growth to promote cooperation between bacteria, which can be further enhanced by the presence of certain plant species. This review aims to give an overview of biofilm processes involved in the detoxification of PCBs including anaerobic and aerobic PCB degradation by bacteria as well as the ability of plants to stimulate microbial activity and degradation (rhizoremediation and phytoremediation.

  14. Enantioseparation and identification for the rationalization of the environmental impact of 4 polychlorinated biphenyls.

    Science.gov (United States)

    Guo, Fangjie; Tang, Qiaozhi; Xie, Jingqian; Zhao, Lu; Liu, Kai; Liu, Weiping

    2018-04-01

    Polychlorinated biphenyls (PCBs) are harmful and persistent organic pollutants that have long been used in industrial manufacturing. Their persistence leads to accumulation in the food chain causing potential toxic effects. As 19 out of 78 of the chiral congeners have stable atropisomers at ambient temperature, we studied some typical enantiomers: PCB45, PCB95, PCB136, and PCB149. The chiral stationary phases OD-H and OJ-H were used for separation in analytic high-performance liquid chromatography (HPLC), as well as for collection in semi-preparative HPLC. The resolution was optimized with respect to n-hexane-based mobile phases, temperature, and flow rate. All pure enantiomers were recovered from semi-preparative HPLC within 15 minutes for practical purpose. Characterization of the absolute configurations were conducted with a combination of theoretical and experimental electronic circular dichroism measurements. The enantiomers of PCB45, PCB95, PCB136, and PCB149 proved to be eluted as R > S, S > R, R > S, and S > R, respectively. Molecular structures (eg, substituent groups) and properties (eg, bond lengths, bond angles, and dipole moments) were quantitatively analyzed to understand the toxicity effect of PCBs. In summary, we have developed a well-established methodology of collection and configuration identification for analogous PCB derivatives. © 2018 Wiley Periodicals, Inc.

  15. Toxicological effects of polychlorinated biphenyls (PCBs) on freshwater turtles in the United States.

    Science.gov (United States)

    Ming-Ch'eng Adams, Clare Isabel; Baker, Joel E; Kjellerup, Birthe V

    2016-07-01

    Prediction of vertebrate health effects originating from persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) has remained a challenge for decades thus making the identification of bioindicators difficult. POPs are predominantly present in soil and sediment, where they adhere to particles due to their hydrophobic characteristics. Animals inhabiting soil and sediment can be exposed to PCBs via dermal exposure while others may obtain PCBs through contaminated trophic interaction. Freshwater turtles can serve as bioindicators due to their strong site fidelity, longevity and varied diet. Previous research observed the health effects of PCBs on turtles such as decreased bone mass, changed sexual development and decreased immune responses through studying both contaminated sites along with laboratory experimentation. Higher deformity rates in juveniles, increased mortality and slower growth have also been observed. Toxicological effects of PCBs vary between species of freshwater turtles and depend on the concertation and configuration of PCB congeners. Evaluation of ecotoxicological effects of PCBs in non-endangered turtles could provide important knowledge about the health effects of endangered turtle species thus inform the design of remediation strategies. In this review, the PCB presence in freshwater turtle habitats and the ecotoxicological effects were investigated with the aim of utilizing the health status to identify areas of focus for freshwater turtle conservation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Non-dioxin like polychlorinated biphenyl indicator congeners in Northwest Atlantic spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    St-Gelais, Adam T; Aeppli, Christoph; Burnell, Craig A; Costa-Pierce, Barry A

    2017-07-15

    In the Northwest Atlantic Ocean (NWAO), spiny dogfish (Squalus acanthias) is a promising commercial species following of collapse of traditional groundfish stocks. There are little available data assessing polychlorinated biphenyls (PCBs) in NWAO spiny dogfish. Here, six non-dioxin like PCB indicator congeners used in European Union regulations (EU NDL-PCB) were quantified via gas chromatography/mass spectrometry in 50 mature male spiny dogfish landed in southern New England. The average total concentration of EU NDL-PCBs was 58±43ng/g (mean±1 standard deviation). PCB values (corrected for co-elution) were below the 200ng/g EU regulatory limit. Results provide first recent regional insight into the PCB content of spiny dogfish in the NWAO. However, our study offers only a snapshot of one particular dogfish population, and might not be representative for the whole NWAO. This study underscores the need for further testing in this species. Copyright © 2017. Published by Elsevier Ltd.

  17. Specific accumulation of polychlorinated biphenyls and organochlorine pesticides in Japanese common squid as a bioindicator

    International Nuclear Information System (INIS)

    Ueno, D.; Inoue, S.; Ikeda, K.; Tanaka, H.; Yamada, H.; Tanabe, S.

    2003-01-01

    Japanese common squid is a suitable bioindicator for monitoring organochlorines pollution in waters around Japan. - Organochlorines (OCs) representing Persistent Organic Pollutants (POPs) such as PCBs (polychlorinated biphenyls), DDTs (DDT and its metabolites), CHLs (chlordane compounds), HCHs (hexachlorocyclohexane isomers) and HCB (hexachlorobenzene) were determined in the liver of Japanese common squid (Todarodes pacificus) collected from the waters around Japan (Japan Sea and western North Pacific Ocean). Among OCs concentrations, PCBs (upto 5600 ng/g lipid wt.) were the highest, and those of other OCs were in the order of DDT> CHLs > HCHs > HCB. Studies on growth trend and seasonal variation of OCs in this species suggest a rapid reflection of the pollution levels in seawater where and when they were collected, regardless of body-length and time of collection. These results indicate that Japanese common squid is a suitable bioindicator for monitoring OCs pollution in waters around Japan. With regard to the geographical distribution of OCs in this species collected from waters around Japan, OCs concentrations in specimens from Japan Sea were higher than those from the Pacific Ocean. This result might reflect some existing of local pollution sources of OCs around Japan Sea, and slower water exchange between Japan Sea and open ocean

  18. Heavy metals and polychlorinated biphenyls (PCBs) sedimentation in the Lianhua Mountain Reservoir, Pearl River Delta, China.

    Science.gov (United States)

    Huang, Jingyu; Amuzu-Sefordzi, Basil; Li, Ming

    2015-05-01

    The Pearl River Delta is one of the biggest electronics manufacturing regions in the world. Due to the presence of abandoned industrial sites and the proliferation of large-scale electronics companies in the past four decades, it is therefore imperative to investigate the extent of heavy metals and polychlorinated biphenyls (PCBs) contamination in the region. Spatial and temporal distribution of heavy metals (Cr, Cu, Ni, Pb, and Zn) and PCBs (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, and PCB180) in the Lianhua Mountain reservoir in the Pearl River Delta, Dongguan City, China were examined based on a sedimentary profile analysis. Higher concentrations of the heavy metals detected were recorded in bottom sediments whereas 70% of the detected PCBs recorded maximum concentrations in top sediments. The geo-accumulation indices (Igeo) indicate that the study area is uncontaminated to moderately contaminated. Also, the integrated pollution indices (IPI) were above 1, except Pb, which shows that the study area is contaminated with heavy metals from anthropogenic sources. The concentrations of individual heavy metals and PCBs over a period of 60 years were also analyzed in order to establish a historical trend of pollution in the study area. This study provides baseline information on the level and historical trend of heavy metals and PCBs pollution in the study area.

  19. Polychlorinated biphenyls in freshwater salmonids from the Kerguelen Islands in the Southern Ocean

    Energy Technology Data Exchange (ETDEWEB)

    Jaffal, A. [Laboratoire d' Eco-Toxicologie, EA 2069 Vignes et Vins de Champagne, Universite de Reims Champagne-Ardenne, F51687 Reims Cedex 2 (France); Givaudan, N. [UMR8079, CNRS, Orsay F-91405 (France); Univ Paris-Sud, Ecologie Systematique et Evolution, Orsay F-91405 (France); Betoulle, S. [Laboratoire d' Eco-Toxicologie, EA 2069 Vignes et Vins de Champagne, Universite de Reims Champagne-Ardenne, F51687 Reims Cedex 2 (France); Terreau, A. [IPEV Institut Polaire Francais, F29280 Plouzane (France); Paris-Palacios, S.; Biagianti-Risbourg, S. [Laboratoire d' Eco-Toxicologie, EA 2069 Vignes et Vins de Champagne, Universite de Reims Champagne-Ardenne, F51687 Reims Cedex 2 (France); Beall, E. [ECOBIOP, UMR 1224 INRA-Universite de Pau-Pays de l' Adour F63310 St-Pee-sur-Nivelle (France); Roche, H., E-mail: helene.roche@u-psud.fr [UMR8079, CNRS, Orsay F-91405 (France); Univ Paris-Sud, Ecologie Systematique et Evolution, Orsay F-91405 (France)

    2011-05-15

    The Subantarctic Kerguelen Islands (49{sup o}S, 70{sup o}E) contain freshwater ecosystems among the most isolated in the world. Concentrations of polychlorinated biphenyls (PCBs) were assessed in the muscle of 48 brook trout and 38 brown trout caught during summer and spring 2006 in the rivers, lakes and ponds of Kerguelen. The sum of 29 PCBs averaged 404 and 358 ng g{sup -1} lipid, and dioxin-like PCB was 19 and 69 ng g{sup -1} lipid, in brook and brown trout, respectively. The values showed a high variability and some fish accumulated PCBs at levels similar to those of fish from impacted areas. While inter-sex differences were limited, the season and the morphotype appeared to have the most influence. Fish captured in summer had muscle PCB concentrations about three times higher than those caught in spring and the 'river' morphotype of brook trout showed the highest PCB levels. - Highlights: > First assessment of PCB contamination of biota in Kerguelen Islands, Sub-Antarctica. > PCB bioaccumulation level in trout varies from very high to undetectable. > Habitat and morphotype are the most influential factors on the variability. > Distribution pattern of PCBs in the muscle of fish is morphotype dependent. - Salmonids in hydrosystems of the Kerguelen Islands (Southern Ocean) show a high PCB bioaccumulation.

  20. Polycyclic aromatic hydrocarbon metabolism in mullets, Chelon labrosus, treated by polychlorinated biphenyls

    International Nuclear Information System (INIS)

    Narbonne, J.F.; Suteau, P.; Daubeze, M.; Audy, C.

    1987-01-01

    Contamination of the ocean by hydrocarbons has become a major environmental problem. Consequently, it is not surprising that residues of potentially toxic xenobiotics, such as benzo(a)pyrene (B(a)P), are present in marine species used as human food. The oxidative metabolism of aromatic hydrocarbons proceeds via intermediate arene oxides. Some of these metabolites are very reactive electrophiles and may interact with cellular macromolecules such as proteins, DNA and RNA. Thus, the ability of an organism to further metabolize arene oxides can be an important protective mechanism against the possible toxic effect of these molecules. The existence of hepatic cytochrome P-450 dependent monooxygenase activities in fish is now well established. The exposure of fish to polychlorinated biphenyls (PCB) increases both the monooxygenase activities and the total amount of cytochrome P-450 in the microsomal fractions of fish liver. The purpose of this study was to compare the toxication-detoxication balance in both control and PCB induced estuarine fish (Grey mullets)

  1. Sex difference in polychlorinated biphenyl concentrations of burbot Lota lota from Lake Erie

    Science.gov (United States)

    Madenjian, C.P.; Stapanian, M.A.; Rediske, R.R.; O’Keefe, J. P.

    2013-01-01

    Whole-fish polychlorinated biphenyl (PCB) concentrations were determined for 25 female and 25 male burbot Lota lota from Lake Erie. Bioenergetics modeling was used to investigate whether the sex difference in growth rate resulted in a difference in gross growth efficiency (GGE) between the sexes. For ages 6–13 years, male burbot averaged 28 % greater PCB concentrations than female burbot. The sex difference in PCB concentrations widened for ages 14–17 years, with male burbot having, on average, 71 % greater PCB concentrations than female burbot. Bioenergetics modeling results showed that the faster growth rate exhibited by female burbot did not lead to greater GGE in female individuals of the younger burbot and that the faster growth by female fish led to female GGE being only 2 % greater than male GGE in older burbot. Although our bioenergetics modeling could not explain the observed sex difference in PCB concentrations, we concluded that a sex difference in GGE was the most plausible explanation for the sex difference in PCB concentrations of burbot ages 6–13 years. Not only are male fish likely to be more active than female fish, but the resting metabolic rate of male fish may be greater than that of female fish. We also concluded that the widening of the sex difference in PCB concentrations for the older burbot may be due to many of the older male burbot spending a substantial amount of time in the vicinity of mouths of rivers contaminated with PCBs.

  2. Oxidation of dibenzothiophene (DBT by Serratia marcescens UCP 1549 formed biphenyl as final product

    Directory of Open Access Journals (Sweden)

    de Araújo Hélvia W

    2012-05-01

    Full Text Available Abstract Background The desulphurization of dibenzothiophene (DBT, a recalcitrant thiophenic fossil fuel component by Serratia marcescens (UCP 1549 in order for reducing the Sulphur content was investigated. The Study was carried out establishing the growth profile using Luria Bertani medium to different concentrations of DBT during 120 hours at 28°C, and orbital Shaker at 150 rpm. Results The results indicated that concentrations of DBT 0.5, 1.0 and 2.0 mM do not affected the growth of the bacterium. The DBT showed similar Minimum Inhibitory Concentration (MIC and Minimum Bactericidal Concentration (MCB (3.68 mM. The desulphurization of DBT by S. marcescens was used with 96 hours of growth on 2 mM of DBT, and was determined by gas chromatography (GC and GC-mass spectrometry. In order to study the desulphurization process by S. marcescens was observed the presence of a sulfur-free product at 16 hours of cultivation. Conclusions The data suggests the use of metabolic pathway “4S” by S. marcescens (UCP 1549 and formed biphenyl. The microbial desulphurization process by Serratia can be suggest significant reducing sulphur content in DBT, and showed promising potential for reduction of the sulfur content in diesel oil.

  3. Distribution of polychlorinated biphenyls in the Housatonic River and adjacent aquifer, Massachusetts

    Science.gov (United States)

    Gay, Frederick B.; Frimpter, Michael H.

    1985-01-01

    Polychlorinated biphenyls (PCB's) are sorbed to the fine-grained stream-bottom sediments along the Housatonic River from Pittsfield, Massachusetts, southward to the Massachusetts-Connecticut boundary. The highest PCB concentrations, up to 140,000 micrograms per kilogram, were found in samples of bottom material from a reach of the river between Pittsfield and Woods Pond Dam in Lee, Massachusetts. Sediments in Woods Pond have been estimated to contain about 11,000 pounds of PCB's. Approximately 490 pounds per year of PCB's have also been estimated to move past the Housatonic River gaging station at Great Barrington. The distribution of hydraulic heads, water temperatures, and concentrations of dissolved oxygen, ammonia, nitrate, iron, and manganese in ground water shows that industrial water-supply wells in a sand and gravel aquifer adjacent to a stretch of the river called Woods Pond have been inducing ground-water recharge through the PCB-contaminated bottom sediments of the pond since late 1956. These data indicate that, at one location along the shore of the pond, the upper 40 feet of the aquifer contains water derived from induced infiltration. However, this induced recharge has not moved PCB's from the bottom sediments into a vertical section of the aquifer located 5 feet downgradient from the edge of Woods Pond. Samples taken at selected intervals in this section showed that no PCB's sorbed to the aquifer material or dissolved in the ground water within the detection limits of the chemical analyses.

  4. Importance of growth rate on mercury and polychlorinated biphenyl bioaccumulation in fish

    Science.gov (United States)

    Li, Jiajia; Haffner, G. Douglas; Patterson, Gordon; Walters, David M.; Burtnyk, Michael D.; Drouillard, Ken G.

    2018-01-01

    To evaluate the effect of fish growth on mercury (Hg) and polychlorinated biphenyl (PCB) bioaccumulation, a non–steady‐state toxicokinetic model, combined with a Wisconsin bioenergetics model, was developed to simulate Hg and PCB bioaccumulation in bluegill (Lepomis macrochirus). The model was validated by comparing observed with predicted Hg and PCB 180 concentrations across 5 age classes from 5 different waterbodies across North America. The non–steady‐state model generated accurate predictions for Hg and PCB bioaccumulation in 3 of 5 waterbodies: Apsey Lake (ON, Canada), Sharbot Lake (ON, Canada), and Stonelick Lake (OH, USA). The poor performance of the model for the Detroit River (MI, USA/ON, Canada) and Lake Hartwell (GA/SC, USA), which are 2 well‐known contaminated sites with possibly high heterogeneity in spatial contamination, was attributed to changes in feeding behavior and/or prey contamination. Model simulations indicate that growth dilution is a major component of contaminant bioaccumulation patterns in fish, especially during early life stages, and was predicted to be more important for hydrophobic PCBs than for Hg. Simulations that considered tissue‐specific growth provided some improvement in model performance particularly for PCBs in fish populations that exhibited changes in their whole‐body lipid content with age. Higher variation in lipid growth compared with that of lean dry protein was also observed between different bluegill populations, which partially explains the greater variation in PCB bioaccumulation slopes compared with Hg across sampling sites.

  5. Atmospheric occurrence, transport and gas-particle partitioning of polychlorinated biphenyls over the northwestern Pacific Ocean

    Science.gov (United States)

    Wu, Zilan; Lin, Tian; Li, Zhongxia; Li, Yuanyuan; Guo, Tianfeng; Guo, Zhigang

    2017-10-01

    Ship-board air samples were collected during March to May 2015 from the East China Sea (ECS) to the northwestern Pacific Ocean (NWP) to explore the atmospheric occurrence and gas-particle partitioning of polychlorinated biphenyls (PCBs) when the westerly East Asian Monsoon prevailed. Total PCB concentrations in the atmosphere ranged from 56.8 to 261 pg m-3. Higher PCB levels were observed off the coast and minor temperature-induced changes showed that continuous emissions from East Asia remain as an important source to the regional atmosphere. A significant relationship between Koa (octanol-air partition coefficient) and KP (gas-particle partition coefficient) for PCBs was observed under continental air masses, suggesting that land-derived organic aerosols affected the PCB gas-particle partitioning after long-range transport, while an absence of this correlation was identified in marine air masses. The PCB partitioning cannot be fully explained by the absorptive mechanism as the predicted KP were found to be 2-3 orders of magnitude lower than the measured Kp, while the prediction was closely matched when soot adsorption was considered. The results suggested the importance of soot carbon as a transport medium for PCBs during their long-range transport and considerable impacts of continental outflows on PCBs across the downwind area. The estimated transport mass of particulate PCBs into the ECS and NWP totals 2333 kg during the spring, constituting ca. 17% of annual emission inventories of unintentionally produced PCB in China.

  6. Dioxin-like polychlorinated biphenyls in marine fish from Shandong, China, and human dietary exposure.

    Science.gov (United States)

    Cao, Yanping; Jiang, Dafeng; Li, Fenghua; Chen, Jindong; Li, Wei; Jiao, Yanni; Li, Lu

    2018-05-22

    The occurrence and human dietary exposure of 12 dioxin-like polychlorinated biphenyls (DL-PCBs) in 41 marine fish samples from Shandong Province of China were investigated. The DL-PCB congeners were extracted using automated Soxhlet extraction, purified via a composite column cleanup procedure and analyzed by gas chromatography-triple quadrupole mass spectrometry. DL-PCB congeners were found in all analyzed samples, with a mean concentration of 0.887 ng/g ww (wet weight). The TEQ concentrations of DL-PCBs in individual fish samples ranged from 0.011 to 9.214 pg WHO TEQ/g ww. The mean dietary intake for all fish species was 36.5 pg TEQ/kg bw/month, which was lower than the provisional tolerable monthly intake of 70 pg TEQ/kg bw/month set by the Joint FAO/WHO Expert Committee on Food Additives. To monitor the trend of DL-PCBs in fish for food safety control it is necessary to maintain a surveillance program.

  7. A review of the neurotoxicity of non-dioxin-like polychlorinated biphenyls

    Energy Technology Data Exchange (ETDEWEB)

    Seegal, R. [Albany Univ., NY (United States). Wadsworth Center, New York State Dept. of Health and School of Public Health

    2004-09-15

    It is perhaps both presumptuous and somewhat nostalgic for me to present research findings from both myself and others describing the changes in central nervous system (CNS) function that occur following exposure to non-dioxin-like polychlorinated biphenyls (PCBs) at the 2004 Dioxin meeting. Presumptuous because my presentation occurs during this meeting where the majority of the research is concerned with the consequences of exposure to dioxins (the most toxic substance produced by man) and nostalgic because, in 1992, I presented some of my earliest work demonstrating that non-dioxin-like PCBs were capable of significantly altering neurochemical function. Much has changed in the intervening twelve years. Laboratories in the United States and Europe now routinely study and describe the neurotoxicological effects of developmental and in vitro exposure to non-dioxin-like PCBs. My task will be to briefly describe the highlights of that research and suggest additional approaches that will hopefully increase our ability to understand the mechanisms of action of non-dioxin-like PCBs on neuronal and behavioral function in populations of exposed humans.

  8. Organochlorine pesticides and polychlorinated biphenyls in herring from the southern Baltic, 1983

    Energy Technology Data Exchange (ETDEWEB)

    Falandysz, J

    1986-02-01

    Hexachlorobenzene (HCB), alpha-, beta-, gamma- and delta-benzenehexachloride (BHC, HCH), p,p'-DDE, o,p'-DDD, o,p'-DDT, p,p'-DDD and p,p'-DDT (sigma DDT) and polychlorinated biphenyls (PCB) levels have been determined in muscle tissue of 187 herring (Clupea harengus) netted during 1983 in a different regions in the southern part of the Baltic Sea. The mean levels found for herring muscle tissue related to wet weight (microgram/kg) were: 14 HCB, 18 alpha-BHC, 23 beta-BHC, 14 gamma-BHC, delta-BHC remained undetected, 56 sigma BHC, 115 p,p'-DDE, o,p'-DDD and o,p'-DDT remained undetected, 84 p,p'-DDD, 51 p,p'-DDT, 250 sigma DDT and 530 PCB. The levels of organochlorine pesticides determined in wet muscles or extractable lipids of herring are nearly 2-3 times as high as those noted in fish sampled in the same area in two years before, while for PCBs the wet weight levels were comparable, and when based on a lipid weight are somewhat higher. The results are compared with levels found in herring collected in different regions of the Baltic Sea during 1965-1983, and reported previously by other authors.

  9. Passive air sampling of polychlorinated biphenyls, organochlorine compounds, and polybrominated diphenyl ethers across Asia.

    Science.gov (United States)

    Jaward, Foday M; Zhang, Gan; Nam, Jae Jak; Sweetman, Andrew J; Obbard, Jeffrey P; Kobara, Yuso; Jones, Kevin C

    2005-11-15

    Asia is of global importance economically, yet data on ambient persistent organic pollutant levels are still sparse for the region, despite international efforts under the Stockholm Convention to identify and reduce emissions. A large-scale passive air sampling survey was therefore conducted in Asia, specifically in China, Japan, South Korea, and Singapore. Polyurethane foam disks were deployed simultaneously at 77 sites, between Sept 21 and Nov 16, 2004, and analyzed for polychlorinated biphenyls (PCBs), organochlorine compounds (hexachlorobenzene (HCB), dichlorodiphenyltrichloroethanes (DDTs), chlordane), and polybrominated diphenyl ethers (PBDEs). The meteorological conditions prevailing in the region at this time facilitated the assessment of local/regional differences in atmospheric emissions, because large-scale advection effects due to monsoons or dust storms did not occur. Air concentrations estimated assuming an average sampler uptake rate of 3.5 m3/day ranged as follows (pg m(-3)): PCBs, 5-340; HCB, 10-460; DDTs, 0.4-1800; chlordanes, 1-660; PBDEs, < 0.13-340. South Korea and Singapore generally had regionally low concentrations. Elevated concentrations of PCBs, DDTs, and HCB occurred at sites in China, higher than reported in a similar recent sampling campaign in Europe. Chlordane was highest in samples from Japan (which also had elevated levels of PCBs and DDTs) and was also elevated in some Chinese locations. PBDE levels were generally low in the region.

  10. Polychlorinated Biphenyls Induce Mitochondrial Dysfunction in SH-SY5Y Neuroblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Stefania Cocco

    Full Text Available Chronic exposure to polychlorinated biphenyls (PCBs, ubiquitous environmental contaminants, can adversely affect the development and function of the nervous system. Here we evaluated the effect of PCB exposure on mitochondrial function using the PCB mixture Aroclor-1254 (A1254 in SH-SY5Y neuroblastoma cells. A 6-hour exposure to A1254 (5 μg/ml reduced cellular ATP production by 45%±7, and mitochondrial membrane potential, detected by TMRE, by 49%±7. Consistently, A1254 significantly decreased oxidative phosphorylation and aerobic glycolysis measured by extracellular flux analyzer. Furthermore, the activity of mitochondrial protein complexes I, II, and IV, but not V (ATPase, measured by BN-PAGE technique, was significantly reduced after 6-hour exposure to A1254. The addition of pyruvic acid during exposure to A1254 significantly prevent A1254-induced cell injury, restoring resting mitochondrial membrane potential, ATP levels, oxidative phosphorylation and aerobic glycolysis. Furthermore, pyruvic acid significantly preserved the activity of mitochondrial complexes I, II and IV and increased basal activity of complex V. Collectively, the present results indicate that the neurotoxicity of A1254 depends on the impairment of oxidative phosphorylation, aerobic glycolysis, and mitochondrial complexes I, II, and IV activity and it was counteracted by pyruvic acid.

  11. Indicator polychlorinated biphenyl residues in muscle tissue of fish from Black Sea coast of Bulgaria

    Directory of Open Access Journals (Sweden)

    S. Georgieva

    2016-06-01

    Full Text Available Abstract. Polychlorinated biphenyls (PCBs are characterized by high lipophilicity and persistence in the environment and will therefore bioaccumulate and biomagnify in the food chain. PCBs were determined in muscle tissue of four fish species: goby (Neogobius melanostomus, horse mackerel (Trachurus Mediterraneus ponticus, shad (Alosa pontica pontica and turbot (Psetta maxima maeotica. Samples were collected from Bulgarian Black Sea coast during 2007 – 2011. The PCBs were analyzed in order to examine the time trends of PCB concentrations in fish from Black Sea. The six individual PCBs congeners were determined by capillary gas chromatography system with mass spectrometry detection. PCBs were found in all fish species at concentrations ranging between 2.32 ng/g ww (wet weight and 32.87 ng/g ww in goby and shad, respectively. PCB profiles have been found to be similar in all the fish species tested. The most abundant PCB congeners in fish species were hexa- and heptachlorinated PCBs 138, 153 and 180. PCB 153 was the dominant congener in all fish studied and were found in the range from 0.95 ng/g ww (horse mackerel 2011 to 11.67 ng/g ww (shad 2010. The sum of six indicator PCBs in all fish species did not exceed the European maximum limit of 75 ng/g ww. The levels of PCBs in fish from Bulgarian Black Sea coast were found lower than in fish species from other seas – the Aegean Sea and the Mediterranean Sea.

  12. Occupational exposure to polychlorinated biphenyls and risk of cutaneous melanoma: a meta-analysis.

    Science.gov (United States)

    Boffetta, Paolo; Catalani, Simona; Tomasi, Cesare; Pira, Enrico; Apostoli, Pietro

    2018-01-01

    The aim of this study was to carry out a meta-analysis of studies on exposure to polychlorinated biphenyls (PCBs) and the risk of malignant melanoma (MM). We searched Scopus, PubMed, and reference lists; among 807 potentially relevant articles, we selected those based on 12 populations. Data were extracted according to a standardized form; the Newcastle-Ottawa Scale was used to assess study quality. Meta-analyses were carried out according to fixed-effect and random-effects models. The fixed-effect summary relative risk (RR) for MM was 0.91 [95% confidence interval (CI): 0.82-1.00]; the random-effects summary RR was 1.05 (95% CI: 0.78-1.32). The random-effects summary RR from eight occupational cohorts was 1.13 (95% CI: 0.91-1.35) and that from four community-based studies was 0.84 (95% CI: 0.36-1.31). The quality of the studies and the methods for PCB exposure assessment did not influence the RR. These results do not support the hypothesis of an association between PCB exposure and the risk of MM.

  13. Contamination by polychlorinated biphenyls (PCBs) in striped dolphins (Stenella coeruleoalba) from the Southeastern Mediterranean Sea.

    Science.gov (United States)

    Storelli, Maria Maddalena; Barone, Grazia; Giacominelli-Stuffler, Roberto; Marcotrigiano, Giuseppe Onofrio

    2012-09-01

    Concentrations of polychlorinated biphenyls (PCBs) including dioxin-like PCBs (non-ortho, PCB 77, PCB 126, and PCB 169 and mono-ortho, PCB 105, PCB 118, and PCB 156) were measured in different organs and tissues (melon, blubber, liver, kidney, lung, heart, and muscle tissue) of striped dolphins (Stenella coeruleoalba) from the Eastern Mediterranean Sea (Adriatic Sea). The mean highest levels were in blubber and melon, followed by liver, kidney, lung, heart, and muscle tissue. PCB profiles were similar in all tissues and organs being dominated by the higher chlorinated homologues (hexa-CBs, 55.8-62.1%; penta-CBs, 15.4-20.0%; and hepta-CB PCB 180, 12.7-16.5%). Major PCBs in all tissues were congeners 138 and 153 collectively accounting for 50.6-58.3% of the total PCB concentrations, followed by PCB 101, 105, 118, and 180 constituting from 27.0% to 31.0%. PCB levels were higher in adult males than in adult females. The estimated 2,3,7,8-TCDD toxic equivalents of non- and mono-ortho PCBs were much higher than the threshold level above which adverse effects have been observed in other marine mammals species, suggesting that striped dolphins in this region are at risk for toxic effects.

  14. Gas chromatography/multiphoton ionization/time-of-flight mass spectrometry of polychlorinated biphenyls

    International Nuclear Information System (INIS)

    Matsui, Taiki; Uchimura, Tomohiro; Imasaka, Totaro

    2011-01-01

    A sample mixture of polychlorinated biphenyls (PCBs) was measured by gas chromatography/multiphoton ionization/time-of-flight mass spectrometry (GC/MPI/TOF-MS) using four types of laser sources. When a fourth harmonic emission (266 nm) of a picosecond Nd:YAG laser (1064 nm) was utilized, highly chlorinated PCBs larger than hepta-CBs were not observed. A fifth harmonic emission (213 nm) of the picosecond Nd:YAG laser allowed the measurement of PCBs from di-CBs to octa-CBs, and the limit of detection (LOD) was several pg for each component of PCBs. The LOD for the total amount of PCBs, which was calculated using the protocol provided by the Ministry of the Environment, Japan, was 1000 pg. The signal intensity of the congeners with chlorine atoms at the ortho positions (non-coplanar PCBs) was enhanced by using the fifth harmonic emission. When the fourth harmonic emission remaining after fifth harmonic generation was simultaneously used, the LOD for total PCBs was improved to 667 pg. The PCB sample was also measured using a third harmonic emission (267 nm) of a femtosecond Ti:sapphire laser (800 nm), providing an LOD of 677 pg. Thus, the two-color beam (266/213 nm) of a picosecond Nd:YAG laser had a comparable, or even slightly superior, performance to the more expensive femtosecond Ti:sapphire laser.

  15. Polychlorinated biphenyl congener patterns in fish near the Hanford Site (Washington State, USA).

    Science.gov (United States)

    Rodenburg, Lisa A; Delistraty, Damon; Meng, Qingyu

    2015-03-03

    It is well-known that absorption, distribution, metabolism, and excretion (ADME) processes in fish can alter polychlorinated biphenyl (PCB) congener patterns in fish, but these patterns have never been investigated using an advanced source-apportionment tool. In this work, PCB congener patterns in freshwater fish were examined with positive matrix factorization (PMF). PCB congeners were quantified via EPA Method 1668 in fillet and carcass of six species in four study areas in the Columbia River near the Hanford Site. Six factors were resolved with PMF2 software. Depletion and enhancement of PCB congeners in factors, relative to Aroclor 1254, suggested biotransformation (via cytochrome P450) and bioaccumulation in fish, respectively. Notable differences were observed among species and across study locations. For example, sturgeon and whitefish exhibited congener patterns consistent with Aroclor weathering, suggesting potential PCB metabolism in these species. In terms of location, average concentration of total PCBs for all species combined was significantly higher (P < 0.05) at Hanford 100 and 300 areas, relative to upriver and downriver study sites. Furthermore, a distinct PCB signature in sturgeon and whitefish, collected at Hanford study areas, suggests that Hanford is a unique PCB source.

  16. Effect of polychlorinated biphenyls on osmoregulatory response and apoptosis in GIFT tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Zheng, Y; Qiu, L; Fan, L; Song, C; Meng, S; Chen, J

    2016-09-02

    In the present study, GIFT tilapia Oreochromis niloticus were exposed to polychlorinated biphenyls (PCBs) for 7, 14, and 21 days. Over the duration of the exposure, genotoxicity and the activity of Na + /K + -ATPase (NKA) and Ca + /Mg + -ATPase (CMA) were measured in the gill, kidney, and intestine, to evaluate changes in osmoregulatory response in O. niloticus. Our results showed significant decreases in organic NKA (except in gill tissues after 0.5 mg/L PCB-exposure) and CMA activity. The results of the genotoxicity assay showed significant increases in atp1a1a, nkcc2 (only in gill tissue), and fxyd7 (except after 21 days of 5 mg/L PCB exposure). We found significant increases in caspase proteins in the liver in the 5-mg/L PCB exposure group, and the transcripts showed dose-dependent increases between treatment groups over the exposure duration. This study presents evidence that chronic exposure to PCB could result in organic osmoregulatory response and hepatic apoptosis in GIFT tilapia.

  17. Concentrations and Toxic Equivalency of Polychlorinated Biphenyls in Polish Wastewater Treatment Plant Effluents.

    Science.gov (United States)

    Urbaniak, Magdalena; Kiedrzyńska, Edyta

    2015-10-01

    Wastewater treatment plants (WWTPs) are widely recognized as important sources of toxic contaminants such as polychlorinated biphenyls (PCBs). An example is given in the present paper, where concentrations of 12 dioxin-like PCBs (dl-PCBs) congeners were investigated in effluents from 14 WWTPs of different sizes, using gas chromatography tandem-mass spectrometry. The results obtained demonstrate that the smallest WWTPs are characterized by the highest total dl-PCB concentration of 102.69 pg/L, roughly twice those of medium-size and large WWTPs, i.e. 41.14 and 48.29 pg/L, respectively. In all cases, the concentrations obtained were generated mostly by increased contributions of PCB-77, PCB-105 and PCB-118 which constituted 48 %-59 % of the mean dl-PCB concentration. The results also reveal a predominance of mono-ortho over non-ortho PCBs. All three types of WWTP effluent were found to have similar toxic equivalency (TEQ) values, ranging from 0.31 for large to 0.37 pg TEQ/L for medium WWTPs.

  18. Polychlorinated biphenyls and polybrominated diphenyl ethers in the North American atmosphere

    International Nuclear Information System (INIS)

    Shen Li; Wania, Frank; Lei, Ying D.; Teixeira, Camilla; Muir, Derek C.G.; Xiao, Hang

    2006-01-01

    To assess the spatial concentration variability of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the atmosphere on a large continental scale, their annually integrated air concentrations were determined in 2000/2001 using XAD-based passive air samplers (PAS). The network included 40 stations in Canada, the United States, Mexico, Belize and Costa Rica, and covered 72 degrees of latitude and longitude. Total concentrations of PCB and PBDE congeners ranged from below the detection limit to 130 ng PAS -1 and 24 ng PAS -1 , respectively. PCBs displayed a large variation between urban, rural and remote sites, whereas PBDEs did not follow such a pattern. Open burning of 'Penta'-containing waste may have contributed to the PBDEs detected in the air samples from rural and remote areas. Air from the Canadian Arctic had a relatively higher percentage of lighter PCB congeners than air sampled in the tropical region, which is interpreted as evidence for global fractionation. - A continental passive air sampling network reveals atmospheric distribution patterns of two classes of industrial chemicals

  19. Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans

    International Nuclear Information System (INIS)

    Lucier, G.W.; Nelson, K.G.; Everson, R.B.; Wong, T.K.; Philpot, R.M.; Tiernan, T.; Taylor, M.; Sunahara, G.I.

    1987-01-01

    These studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed Yu-Cheng in Chinese. Based on data from experimental animals models, the authors examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. They also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. The results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties. Two PCDF congeners were detected in Yu-Cheng placentae but not controls. Several PCBs were also detected in much higher concentrations in Yu-Cheng placentae. Surprisingly, placental concentrations of PCBs correlated better with effects than did the PCDFs. The findings are discussed in relation to the risk assessment process

  20. Importance of passive diffusion in the uptake of polychlorinated biphenyls by phagotrophic protozoa

    Energy Technology Data Exchange (ETDEWEB)

    Kujawinski, E.B.; Farrington, J.W.; Moffett, J.W.

    2000-05-01

    Unicellular protozoan grazers represent a size class of organisms where a transition in the mechanism of chlorobiphenyl (CB) introduction, from diffusion through surface membranes to ingestion of contaminated prey, could occur. This study compares the relative importance of these two processes in the overall uptake of polychlorinated biphenyls by protists. Uptake rates and steady-state concentrations were compared in laboratory cultures of grazing and nongrazing protozoa. These experiments were conducted with a 10-{micro}m marine scuticociliate (Uronema sp.), bacterial prey (Halomonas halodurans), and a suite of 21 CB congeners spanning a range of aqueous solubilities. The dominant pathway of CB uptake by both grazing and nongrazing protozoa was diffusion. Organic-carbon-normalized CB concentrations (in the protozoan cell) were equivalent in grazing and nongrazing protozoa for all congeners studied. Rate constants for uptake into and loss from the protozoan cell were independently determined by using [3,3{prime}, 4,4{prime}-{sup 14}C]tetrachlorobiphenyl (IUPAC no. 77), 0.38 {+-} 0.03 min{sup {minus}1} and (1.1 {+-} 0.1) x 10{sup {minus}5} (g of organic carbon){minus}{sup {minus}1} min{sup {minus}1}, respectively. Magnitudes of the uptake and loss processes were calculated and compared by using a numerical model. The model result was consistent with data from the bioaccumulation experiment and supported the hypothesis that diffusive uptake is faster than ingestive uptake in phagotrophic unicellular protozoa.

  1. Age-related polychlorinated biphenyl dynamics in immature bull sharks (Carcharhinus leucas).

    Science.gov (United States)

    Olin, Jill A; Beaudry, Marina; Fisk, Aaron T; Paterson, Gordon

    2014-01-01

    Polychlorinated biphenyls (PCBs) were quantified in liver tissues of bull sharks (Carcharhinus leucas) ranging in age from 3 yr. Summed values of PCBs (ΣPCBs) ranged from 310 ng/g to 22 070 ng/g (lipid wt) across age classes with ΣPCB concentrations for the youngest sharks in the present study (3-yr-old sharks, highlighting the extent of exposure of this young life stage to this class of persistent organic pollutants (POPs). Age normalization of PCB congener concentrations to those measured for the youngest sharks demonstrated a significant hydrophobicity (log octanol/water partition coefficient [KOW ]) effect that was indicative of maternal offloading of highly hydrophobic (log KOW ≥6.5) congeners to the youngest individuals. A distinct shift in the PCB congener profiles was also observed as these young sharks grew in size. This shift was consistent with a transition from the maternally offloaded signal to the initiation of exogenous feeding and the contributions of mechanisms including growth dilution and whole-body elimination. These results add to the growing pool of literature documenting substantially high concentrations of POPs in juvenile sharks that are most likely attributable to maternal offloading. Collectively, such results underscore the potential vulnerability of young sharks to POP exposure and pose additional concerns for shark-conservation efforts. © 2013 SETAC.

  2. Presence of polychlorinated biphenyls (PCBs) in bottled drinking water in Mexico City.

    Science.gov (United States)

    Salinas, Rutilio Ortiz; Bermudez, Beatriz Schettino; Tolentino, Rey Gutiérrez; Gonzalez, Gilberto Díaz; Vega y León, Salvador

    2010-10-01

    This paper describes the concentrations of seven polychlorinated biphenyls (PCBs) in bottled drinking water samples that were collected over 1 year from Mexico City in two sizes (1.5 and 19 L), using gas chromatography with an electron capture detector. PCBs 28 (0.018-0.042 μg/L), 52 (0.006-0.015 μg/L) and 101 (0.001-0.039 μg/L) were the most commonly found and were present in the majority of the samples. However, total concentrations of PCBs in bottled drinking water (0.035-0.039 μg/L) were below the maximum permissible level of 0.50 μg/L stated in Mexican regulations and probably do not represent a hazard to human health. PCBs were detectable in all samples and we recommend a monitoring program be established to better understand the quality of drinking bottled water over time; this may help in producing solutions for reducing the presence of organic contaminants.

  3. Detailed analysis of polybrominated biphenyl congeners in bird eggs from Norway

    International Nuclear Information System (INIS)

    Vetter, Walter; Recke, Roland von der; Herzke, Dorte; Nygard, Torgeir

    2008-01-01

    Individual eggs of six species of birds from Norway representing different food chains were analysed for residues of polybrominated biphenyls (PBBs). In all species, the residue pattern was dominated by hexaBBs. The dominating congeners were PBB 153, PBB 154, and PBB 155. Whereas PBB 153 is present in technical hexabromobiphenyl, PBB 154 and PBB 155 are formed by the reductive debromination of decabromobiphenyl. This was evidenced by the detection of several heptaBBs and octaBBs all of which are typical degradation intermediates of PBB 209. Hepta- and octaBBs were more than one order of magnitude less abundant than the hexaBBs. The second most prevailing homologue group was pentaBBs. The most relevant pentabrominated isomers were PBB 99 and PBB 101. Concentrations of the three hexaBBs - PBB 153, PBB 154, and PBB 155 - amounted to 1.3-13 ng/g wet weight or 3-23% of the contamination with polybrominated diphenyl ethers. - We provide for the first time detailed information on the PBB congeners present in eggs of bird of prey, and quantified three hexabromo congeners

  4. Uptake of polychlorinated biphenyls and organochlorine pesticides from soil and air into radishes (Raphanus sativus)

    Energy Technology Data Exchange (ETDEWEB)

    Mikes, Ondrej; Cupr, Pavel [RECETOX, Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk University, Kamenice 126/3, 625 00 Brno (Czech Republic); Trapp, Stefan [Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, DK-2800 Kgs. Lyngby (Denmark); Klanova, Jana [RECETOX, Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk University, Kamenice 126/3, 625 00 Brno (Czech Republic)], E-mail: klanova@recetox.muni.cz

    2009-02-15

    Uptake of organochlorine pesticides and polychlorinated biphenyls from soil and air into radishes was measured at a heavily contaminated field site. The highest contaminant concentrations were found for DDT and its metabolites, and for {beta}-hexachlorocyclohexane. Bioconcentration factor (BCF, defined as a ratio between the contaminant concentration in the plant tissue and concentration in soil) was determined for roots, edible bulbs and shoots. Root BCF values were constant and not correlated to log K{sub OW}. A negative correlation between BCF and log K{sub OW} was found for edible bulbs. Shoot BCF values were rather constant and varied between 0.01 and 0.22. Resuspended soil particles may facilitate the transport of chemicals from soil to shoots. Elevated POP concentrations found in shoots of radishes grown in the control plot support the hypothesis that the uptake from air was more significant for shoots than the one from soil. The uptake of POPs from air was within the range of theoretical values predicted from log K{sub OA}. - Uptake from air represented for majority of persistent organochlorines a dominant pathway into shoots while uptake from soil was dominant for roots.

  5. Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls.

    Science.gov (United States)

    Mochizuki, H; Oda, H; Yokogoshi, H

    2000-04-01

    The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.

  6. Inhibition of LPS-induced splenocyte proliferation by ortho-substituted polychlorinated biphenyl congeners

    International Nuclear Information System (INIS)

    Smithwick, L. Ashley; Smith, Andrew; Quensen, John F.; Stack, Allison; London, Lucille; Morris, Pamela J.

    2003-01-01

    Polychlorinated biphenyls (PCBs) are persistent environmental contaminants, and their ubiquitous nature has prompted studies of their potential health hazards. As a result of their lipophilic nature, PCBs accumulate in breast milk and subsequently affect the health of offspring of exposed individuals. Biological effects of PCBs in animals have mostly been attributed to coplanar congeners, although effects of ortho congeners also have been demonstrated. To investigate the relationship of immunotoxicity and chlorine substitution pattern, the effects of PCB congeners and mixtures of ortho and non-ortho-substituted constituents of Aroclor 1242 on splenocytes from C57B1/6 mice were examined. The immunotoxic endpoints investigated included splenocyte viability, lipopolysaccharide (LPS)-induced splenocyte proliferation, and LPS-induced antibody secretion. Congeners with multiple ortho chlorines preferentially inhibited splenocyte proliferation as compared with non- or mono-ortho-substituted congeners. However, mixtures of non- and mono-ortho-substituted congeners and multi-ortho-substituted congeners inhibited LPS-induced splenocyte proliferation and antibody secretion at similar concentrations. Exposure of splenocytes to these mixtures did not activate the aryl hydrocarbon receptor (AhR) signal transduction pathway. These results suggest individual multi-ortho-substituted congeners preferentially inhibit LPS-induced splenocyte proliferation, while congeners not exhibiting an effect individually may have additive effects in a mixture to produce an immunotoxic response through an AhR-independent pathway

  7. Polychlorinated biphenyls in alfalfa: Accumulation, sorption and speciation in different plant parts.

    Science.gov (United States)

    Teng, Ying; Sun, Xianghui; Zhu, Lingjia; Christie, Peter; Luo, Yongming

    2017-08-03

    The accumulation, chemical speciation and distribution of polychlorinated biphenyls (PCBs) were investigated in various parts of alfalfa. Moreover, the adsorption characteristics for PCB 28 by alfalfa and the influencing factors of the adsorption characteristics were studied. There were different degrees of PCB accumulation in alfalfa roots, root nodules and shoots. The decreasing order of the accumulation of PCBs in plant tissues was root nodules > roots > shoots, and the decreasing order of the total PCB contents was roots > shoots > root nodules, indicating that the roots were the main sink for PCB accumulation. There were three modes of PCB speciation in alfalfa roots and root nodules, comprising strong sorption (78%) and weak sorption (19%) on tissue surfaces and absorption within tissues (2%). The adsorption isotherms of PCB 28 indicate that the adsorption capacities of root nodules and shoots were both significantly higher than that of the roots. Both lipids and carbohydrates, and especially lipids, affected the PCB adsorption capacities of the tissues. These results may help in the elucidation of the mechanisms of sorption and accumulation of PCBs in the plants and their main influencing factors and thus contribute to the development of phytoremediation technologies for PCB-contaminated soils.

  8. Advances and perspective in bioremediation of polychlorinated biphenyl-contaminated soils.

    Science.gov (United States)

    Sharma, Jitendra K; Gautam, Ravindra K; Nanekar, Sneha V; Weber, Roland; Singh, Brajesh K; Singh, Sanjeev K; Juwarkar, Asha A

    2018-06-01

    In recent years, microbial degradation and bioremediation approaches of polychlorinated biphenyls (PCBs) have been studied extensively considering their toxicity, carcinogenicity and persistency potential in the environment. In this direction, different catabolic enzymes have been identified and reported for biodegradation of different PCB congeners along with optimization of biological processes. A genome analysis of PCB-degrading bacteria has led in an improved understanding of their metabolic potential and adaptation to stressful conditions. However, many stones in this area are left unturned. For example, the role and diversity of uncultivable microbes in PCB degradation are still not fully understood. Improved knowledge and understanding on this front will open up new avenues for improved bioremediation technologies which will bring economic, environmental and societal benefits. This article highlights on recent advances in bioremediation of PCBs in soil. It is demonstrated that bioremediation is the most effective and innovative technology which includes biostimulation, bioaugmentation, phytoremediation and rhizoremediation and acts as a model solution for pollution abatement. More recently, transgenic plants and genetically modified microorganisms have proved to be revolutionary in the bioremediation of PCBs. Additionally, other important aspects such as pretreatment using chemical/physical agents for enhanced biodegradation are also addressed. Efforts have been made to identify challenges, research gaps and necessary approaches which in future, can be harnessed for successful use of bioremediation under field conditions. Emphases have been given on the quality/efficiency of bioremediation technology and its related cost which determines its ultimate acceptability.

  9. Congener-specific egg contribution of polychlorinated biphenyls to nestlings in two passerine species

    Energy Technology Data Exchange (ETDEWEB)

    Maul, Jonathan D., E-mail: jonathan.maul@tiehh.ttu.ed [Department of Environmental Toxicology, Institute of Environmental and Human Health (TIEHH), Texas Tech University, Lubbock, TX 79409 (United States); Schuler, Lance J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University, Carbondale, IL 62901 (United States); Halbrook, Richard S. [Cooperative Wildlife Research Laboratory and Department of Zoology, Southern Illinois University, Carbondale, IL 62901 (United States); Lydy, Michael J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University, Carbondale, IL 62901 (United States)

    2010-08-15

    Quantifying polychlorinated biphenyl (PCB) residues in nestlings of avian species is a common method for assessing trophic transfer and risk at PCB-contaminated sites. The proportion of nestling PCB mass due to maternal transfer is often accounted for by subtracting total PCB mass in eggs from nestlings. However, variation in physicochemical properties and metabolism among congeners may lead to differences between egg contribution based on total PCBs and dioxin-like congeners. We examined congener-specific variation in contribution of PCBs from eggs to nestlings in tree swallows and European starlings. Egg contribution of total PCB mass was 14.3 and 16.2%, respectively, whereas contribution based on dioxin-like congeners was 14.8 and 13.6%, respectively. These data suggest that using total PCB mass in eggs to adjust estimates of PCB accumulation in nestlings may not reflect patterns for dioxin-like congeners, potentially over or under-estimating the risk of toxicity of PCBs. - Congener-specific contribution of PCBs from egg to nestlings was examined.

  10. Polychlorinated biphenyls in polysulfide sealants-Occurrence and emission from a landfill station

    International Nuclear Information System (INIS)

    Persson, N. Johan; Pettersen, Harald; Ishaq, Rasha; Axelman, Johan; Bandh, Cecilia; Broman, Dag; Zebuehr, Yngve; Hammar, Tommy

    2005-01-01

    Approximately 80 000 kg polysulfide sealant containing 10 000-18 000 kg polychlorinated biphenyls (PCB) was deposited at a Swedish municipal landfill station during 1965-1973. Investigations during 1994 showed that soil layers underneath the landfill had concentration of PCB not alarmingly high. The concentration of PCB congeners in ground water samples was elevated 4-750 times compared to a reference sample. Based on samples of ground water, leachate water, and flux chambers measuring evaporation of PCB from the landfill surface, the emission of PCB was estimated to be 1 g ΣPCB/yr. This very low rate was attributed to the high sorptive capacity of the sealant. Compared to a reference site, the evaporation flux was elevated for the most volatile congeners, but factors 20-1400 lower than from another landfill which was contaminated with PCB in paper-pulp fibres. - From a municipal 2-ha landfill containing 10-18 tonnes of ΣPCB bound in polysulfide sealants, only 1 g per year escape to the surroundings

  11. Polychlorinated biphenyls in freshwater salmonids from the Kerguelen Islands in the Southern Ocean

    International Nuclear Information System (INIS)

    Jaffal, A.; Givaudan, N.; Betoulle, S.; Terreau, A.; Paris-Palacios, S.; Biagianti-Risbourg, S.; Beall, E.; Roche, H.

    2011-01-01

    The Subantarctic Kerguelen Islands (49 o S, 70 o E) contain freshwater ecosystems among the most isolated in the world. Concentrations of polychlorinated biphenyls (PCBs) were assessed in the muscle of 48 brook trout and 38 brown trout caught during summer and spring 2006 in the rivers, lakes and ponds of Kerguelen. The sum of 29 PCBs averaged 404 and 358 ng g -1 lipid, and dioxin-like PCB was 19 and 69 ng g -1 lipid, in brook and brown trout, respectively. The values showed a high variability and some fish accumulated PCBs at levels similar to those of fish from impacted areas. While inter-sex differences were limited, the season and the morphotype appeared to have the most influence. Fish captured in summer had muscle PCB concentrations about three times higher than those caught in spring and the 'river' morphotype of brook trout showed the highest PCB levels. - Highlights: → First assessment of PCB contamination of biota in Kerguelen Islands, Sub-Antarctica. → PCB bioaccumulation level in trout varies from very high to undetectable. → Habitat and morphotype are the most influential factors on the variability. → Distribution pattern of PCBs in the muscle of fish is morphotype dependent. - Salmonids in hydrosystems of the Kerguelen Islands (Southern Ocean) show a high PCB bioaccumulation.

  12. High-pressure extraction of polychlorinated biphenyls from soils and other fine-grained solids

    International Nuclear Information System (INIS)

    Markowz, G.

    1996-12-01

    Four doped and three really contaminated samples were subjected to high-pressure PCB (polychlorinated biphenyl) extraction in a laboratory-scale experimental plant using CO 2 (carbon dioxide) as solvent. The PCB levels (sum out of the six key substances) of the real samples were 2.6, 6.8, and 139 mg/kg. The success of the cleaning process was determined by measuring the residual PCB levels in the soil after the extraction. Parameters were varied and samples were taken selectively from various points in the bed (length 270 mm, diameter 14 mm, weighed - in soil 50-60 g) in order to gain an idea of the effects of upscaling. The following parameters were varied: extraction temperature 40-90 C; extraction pressure 200-300 bar; CO 2 flow rate 3.6-14.6 g/min; CO 2 quantity 0-328 g; degree of contamination (doped samples) 12-60 mg/kg; soil moisture 0-15%; particle size 0-2000 μm; entraining agent methanol, ethanol, acetone; proportion of entraining agent 0-7.5% by weight. Furthermore the influence of moisture at the time of doping on extraction was examined. (orig./ABI) [de

  13. Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults

    DEFF Research Database (Denmark)

    Petersen, Maria Skaalum; Halling, Jónrit; Damkier, Per

    2007-01-01

    The CYP3A4 enzyme is, along with other cytochrome P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(o-chlorophenyl), 2-(p'-chlorophenyl)ethane (o,p'-DDT) and 1......,1,-dichloro-2,2-bis (p-chlorophenyl)ethene (p,p'-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3......A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18-60 years, the CYP3A4 activity was determined based on the urinary 6beta-hydroxycortisol/cortisol (6beta...

  14. Cloning the bacterial bphC gene into Nicotiana tabacum to improve the efficiency of phytoremediation of polychlorinated biphenyls

    Czech Academy of Sciences Publication Activity Database

    Nováková, Martina; Macková, M.; Antošová, Z.; Viktorová, J.; Szekeres, M.; Demnerová, K.; Macek, Tomáš

    2010-01-01

    Roč. 1, č. 6 (2010), s. 419-423 ISSN 1949-1018 R&D Projects: GA MŠk 1M06030 Grant - others:GA MŠk(CZ) ME09024 Institutional research plan: CEZ:AV0Z40550506 Keywords : phytoremediation * transgenic plant * Nicotiana tabacum * bphC Subject RIV: EI - Biotechnology ; Bionics

  15. Replacement of two amino acids of 9R-dioxygenase-allene oxide synthase of Aspergillus niger inverts the chirality of the hydroperoxide and the allene oxide.

    Science.gov (United States)

    Sooman, Linda; Wennman, Anneli; Hamberg, Mats; Hoffmann, Inga; Oliw, Ernst H

    2016-02-01

    The genome of Aspergillus niger codes for a fusion protein (EHA25900), which can be aligned with ~50% sequence identity to 9S-dioxygenase (DOX)-allene oxide synthase (AOS) of Fusarium oxysporum, homologues of the Fusarium and Colletotrichum complexes and with over 62% sequence identity to homologues of Aspergilli, including (DOX)-9R-AOS of Aspergillus terreus. The aims were to characterize the enzymatic activities of EHA25900 and to identify crucial amino acids for the stereospecificity. Recombinant EHA25900 oxidized 18:2n-6 sequentially to 9R-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HPODE) and to a 9R(10)-allene oxide. 9S- and 9R-DOX-AOS catalyze abstraction of the pro-R hydrogen at C-11, but the direction of oxygen insertion differs. A comparison between twelve 9-DOX domains of 9S- and 9R-DOX-AOS revealed conserved amino acid differences, which could contribute to the chirality of products. The Gly616Ile replacement of 9R-DOX-AOS (A. niger) increased the biosynthesis of 9S-HPODE and the 9S(10)-allene oxide, whereas the Phe627Leu replacement led to biosynthesis of 9S-HPODE and the 9S(10)-allene oxide as main products. The double mutant (Gly616Ile, Phe627Leu) formed over 90% of the 9S stereoisomer of HPODE. 9S-HPODE was formed by antarafacial hydrogen abstraction and oxygen insertion, i.e., the original H-abstraction was retained but the product chirality was altered. We conclude that 9R-DOX-AOS can be altered to 9S-DOX-AOS by replacement of two amino acids (Gly616Ile, Phe627Leu) in the DOX domain. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation.

    Science.gov (United States)

    Wang, Xinxuan; Feng, Zhihui; Li, Qimeng; Yi, Baicheng; Xu, Qiong

    2018-04-13

    Dental pulp inflammation is a bacterially driven inflammation process characterized by the local accumulation of cytokines/chemokines that participate in destructive processes in the pulp. Multiple mechanisms are involved in dental pulp inflammation, including epigenetic events, such as DNA methylation/demethylation. Ten-eleven translocation 2 (TET2) is a recently discovered DNA methylcytosine dioxygenase that plays important roles in inflammatory disease. However, its role in the inflammatory response of dental pulp is unknown. We observed elevated mRNA and protein levels of TET2 after lipopolysaccharide (LPS) stimulation in human dental pulp cells (hDPCs). To identify the effects of TET2 on cytokine expression, TET2 was knocked down and cytokines were detected using a cytokine antibody array after LPS stimulation. The protein expression of GM-CSF, IL-6, IL-8 and RANTES decreased in the LPS-induced hDPCs following TET2 knockdown. The downregulated expression levels of IL-6 and IL-8 were further confirmed by real-time quantitative polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally, the phosphorylation levels of IKK-α/β, p65 and IκBα of the NF-κB signaling pathway were decreased in the TET2-silenced group. Furthermore, the global 5-hydroxymethylcytosine (5hmC) level was significantly decreased and the genomic 5-methylcytosine (5mC) level was increased in the TET2-deficient hDPCs; TET2 depletion resulted in a decrease in the 5hmC level of the MyD88 promoter following LPS stimulation. These findings indicate that TET2 knockdown inhibits LPS-induced inflammatory response in hDPCs by downregulating MyD88 hydroxymethylation. Thus, TET2-dependent DNA demethylation might play an important role in dental pulp inflammation as an epigenetic regulator.

  17. A CD8 T Cell/Indoleamine 2,3-Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus

    Science.gov (United States)

    Wang, Dandan; Feng, Xuebing; Lu, Lin; Konkel, Joanne E; Zhang, Huayong; Chen, Zhiyong; Li, Xia; Gao, Xiang; Lu, Liwei; Shi, Songtao; Chen, Wanjun; Sun, Lingyun

    2014-01-01

    Objective Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. Methods The effects of allogeneic umbilical cord–derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC–mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation. Results Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow–derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients. Conclusion We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients. PMID:24756936

  18. Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations.

    Science.gov (United States)

    Song, Xudan; Lu, Jiarui; Lai, Wenzhen

    2017-08-02

    Herein, we use in-protein quantum mechanical/molecular mechanical (QM/MM) calculations to elucidate the mechanism of dioxygen activation, oxygen atom exchange and substrate epoxidation processes by AsqJ, an Fe II /α-ketoglutarate-dependent dioxygenase (α-KGD) using a 2-His-1-Asp facial triad. Our results demonstrated that the whole reaction proceeds through a quintet surface. The dioxygen activation by AsqJ leads to a quintet penta-coordinated Fe IV -oxo species, which has a square pyramidal geometry with the oxo group trans to His134. This penta-coordinated Fe IV -oxo species is not the reactive one in the substrate epoxidation reaction since its oxo group is pointing away from the target C[double bond, length as m-dash]C bond. Instead, it can undergo the oxo group isomerization followed by water binding or the water binding followed by oxygen atom exchange to form the reactive hexa-coordinated Fe IV -oxo species with the oxo group trans to His211. The calculated parameters of Mössbauer spectra for this hexa-coordinated Fe IV -oxo intermediate are in excellent agreement with the experimental values, suggesting that it is most likely the experimentally trapped species. The calculated energetics indicated that the rate-limiting step is the substrate C[double bond, length as m-dash]C bond activation. This work improves our understanding of the dioxygen activation by α-KGD and provides important structural information about the reactive Fe IV -oxo species.

  19. Co-operative intermolecular kinetics of 2-oxoglutarate dependent dioxygenases may be essential for system-level regulation of plant cell physiology.

    Science.gov (United States)

    Kundu, Siddhartha

    2015-01-01

    Can the stimulus-driven synergistic association of 2-oxoglutarate dependent dioxygenases be influenced by the kinetic parameters of binding and catalysis?In this manuscript, I posit that these indices are necessary and specific for a particular stimulus, and are key determinants of a dynamic clustering that may function to mitigate the effects of this trigger. The protein(s)/sequence(s) that comprise this group are representative of all major kingdoms of life, and catalyze a generic hydroxylation, which is, in most cases accompanied by a specialized conversion of the substrate molecule. Iron is an essential co-factor for this transformation and the response to waning levels is systemic, and mandates the simultaneous participation of molecular sensors, transporters, and signal transducers. Here, I present a proof-of-concept model, that an evolving molecular network of 2OG-dependent enzymes can maintain iron homeostasis in the cytosol of root hair cells of members of the family Gramineae by actuating a non-reductive compensatory chelation by the phytosiderophores. Regression models of empirically available kinetic data (iron and alpha-ketoglutarate) were formulated, analyzed, and compared. The results, when viewed in context of the superfamily responding as a unit, suggest that members can indeed, work together to accomplish system-level function. This is achieved by the establishment of transient metabolic conduits, wherein the flux is dictated by kinetic compatibility of the participating enzymes. The approach adopted, i.e., predictive mathematical modeling, is integral to the hypothesis-driven acquisition of experimental data points and, in association with suitable visualization aids may be utilized for exploring complex plant biochemical systems.

  20. Purification and site-directed mutagenesis of linoleate 9S-dioxygenase-allene oxide synthase of Fusarium oxysporum confirms the oxygenation mechanism.

    Science.gov (United States)

    Chen, Yang; Jernerén, Fredrik; Oliw, Ernst H

    2017-07-01

    Plants and fungi form jasmonic acid from α-linolenic acid. The first two steps of biosynthesis in plants occur by sequential transformation by 13S-lipoxygenase and allene oxide synthase (AOS). The biosynthesis in fungi may follow this classical scheme, but the only fungal AOS discovered so far are cytochromes P450 (CYP) fused to 8- and 9-dioxygenases (DOX). In the present report, we purified recombinant 9S-DOX-AOS of Fusarium oxysporum from cell lysate by cobalt affinity chromatography to near homogeneity and studied key residues by site-directed mutagenesis. Sequence homology with 8R-DOX-linoleate diol synthases (8R-DOX-LDS) suggested that Tyr414 catalyzes hydrogen abstraction and that Cys1051 forms the heme thiolate ligand. Site-directed mutagenesis (Tyr414Phe; Cys1051Ser) led to loss of 9S-DOX and 9S-AOS activities, respectively, but other important residues in the CYP parts of 5,8- and 7,8-LDS or 9R-AOS were not conserved. The UV-visible spectrum of 9S-DOX-AOS showed a Soret band at 409 nm, which shifted to 413 nm in the Cys1051Ser mutant. The 9S-AOS of the Tyr414Phe mutant transformed 9S-hydroperoxides of α-linolenic and linoleic acids to allene oxides/α-ketols, but it did not transform 13-hydroperoxides. We conclude that 9S- and 8R-DOX catalyze hydrogen abstraction at C-11 and C-8, respectively, by homologous Tyr residues. Copyright © 2017 Elsevier Inc. All rights reserved.